Cardiovascular diseases

More than 170 clinicians from diverse healthcare backgrounds attended the National Institute of Clinical Studies (NICS) “Heart Failure Forum 2004: improving outcomes in chronic care”, held in Canberra, 7–8 June 2004. The purpose of the forum was to raise awareness of the growing burden of heart failure, engage with Australian and international experts in heart failure and chronic care management, and explore strategies for improving outcomes in chronic care. Successful models of careGeoffrey Tofler (Chair of the NICS Heart Failure Advisory Group and Professor of Preventive Cardiology, University of Sydney) set the scene by highlighting gaps in the current medical treatment of heart failure. These gaps are most notable in the use of evidence-based drug therapies, such as angiotensin-converting enzyme (ACE) inhibitors and β-blockers, that reduce symptoms and hospital admissions and improve survival.1 Chronic care expert Ed Wagner (Director, MacColl Institute for Healthcare Innovation, Group Health Cooperative, Seattle, Washington, US, and leader of the Robert Wood Johnson Foundation Improving Chronic Illness Care Program) argued that the current care system is not working adequately for either patients or healthcare professionals,2 and emphasised the importance of redesigning care systems around the needs of patients with chronic illnesses. He described the essential elements of the chronic care model (Box 1),3 and illustrated how the model, combined with the Institute of Healthcare Improvement collaborative improvement method, enabled over 1000 US healthcare organisations to improve quality of care for patients with asthma, diabetes and chronic heart failure.4 Peter Didsbury (Chairman, New Zealand Guidelines Group, and Deputy Head and Manager of Integration, ProCare Health Ltd, Wellington, NZ) reported increased prescribing of ACE inhibitors, β-blockers and spironolactones following multifaceted intervention strategies, such as improved access to echocardiography, rapid access to cardiology advice, funding for β-blocker titration, access to a cardiac nurse specialist and 24-hour telephone triage. The results of an unpublished randomised trial he conducted involving patients with chronic obstructive pulmonary disease led him to suggest that improving the effectiveness of patient adherence through more structured care processes (such as holistic assessments, education about the condition, lifestyle therapy, action plans and active follow-up) may have greater effect. The vital role played by nursing staff was highlighted by Simon Stewart (Chair, Cardiovascular Nursing, and Director of the Centre for Innovation in Health, University of South Australia). He presented evidence from a recent systematic review of randomised trials of multidisciplinary strategies for the management of patients with heart failure at high risk for admission. This review showed that programs that incorporate follow-up by a specialised multidisciplinary team (in either a clinic or a non-clinic setting) reduce mortality, heart failure hospitalisations and all-cause hospitalisations.5 Stewart emphasised the need for a more systematic implementation of specialist nurse-led, home-based, follow-up services after discharge for patients with heart failure. Such services are currently available to less than 10% of those needing them. Whether this form of care is applicable in rural and remote locations is not certain, according to Henry Krum (Director, NHMRC Centre of Clinical Research Excellence in Therapeutics, Monash University), who described the computerised, telephone-based patient support system (“Telewatch”) his research group is trialling in Australia. The system allows healthcare providers to closely monitor symptoms of patients with chronic heart failure and to track progress, respond to deterioration and make suggestions to improve overall management. Specific questions relate to diet, exercise, alcohol use, smoking, use of drugs for chronic heart failure, use of prescribed and over-the-counter medications unrelated to chronic heart failure, mood state and current coping. Results are expected by the end of 2005. The role of GPs in management of heart failureAlthough heart failure is a leading medical cause of hospital admissions in older people, Justin Beilby (Head, Department of General Practice, University of Adelaide) noted that patients with heart failure represent a low proportion of the total patients that each general practitioner treats. Of concern to GPs is the need to identify people with early heart failure, who would benefit from more aggressive intervention. This point was reinforced by Michael Feneley (Chair, Cardiac Society of Australia and New Zealand Echocardiography Working Group), who stressed that new shortness of breath with no other obvious cause is often a symptom of early heart failure and should trigger investigation. He believes echocardiography is the most useful investigation in confirming or ruling out heart failure and is critical for determining the underlying cause and guiding therapy.6 Mark Harris (Professor, General Practice, University of New South Wales) detailed the important role of Divisions of General Practice in providing support and feedback to practices in the collection and analysis of data and in the use of patient registries — key elements of proactive chronic care patient management. The forum heard from Judith Mackson (Prescribing Program Coordinator, National Prescribing Service [NPS]) that the NPS, the National Heart Foundation of Australia (NHFA) and the NICS have formed a collaboration to improve targeted elements of heart failure diagnosis and management in general practice. This joint program will deliver key messages on drug use for treating heart failure and will emphasise the importance of echocardiography to confirm the diagnosis and guide treatment. Current government initiatives in chronic careThe importance of adopting a more systematic approach to chronic care management in Australia was reinforced by Andrew Tonkin (Director, Health, Medical and Scientific Affairs, NHFA), who argued that the effective management of heart failure represents an excellent paradigm for improving the care of people with other chronic conditions. The value and cost-effectiveness of management programs that can support patients with heart failure in the home and community and prevent hospitalisation have been demonstrated. Programs and information systems for patients with heart failure, once established, could be easily adapted to the needs of other chronically ill patients. Jane Halton (Secretary, Australian Government Department of Health and Ageing) highlighted recent Budget initiatives. Funding is provided for 1600 more primary care nurses and a new Medicare Benefits Schedule item number linked to the Enhanced Primary Care multidisciplinary care plan for services provided by allied health professionals. Ms Halton outlined the government’s plans for a national chronic disease strategy, following development and consultations by the National Health Priority Action Council’s Chronic Disease Strategy Group. The forum heard about different state heart failure programs. Craig White (Deputy Chair, Victorian Hospital Admission Risk Prevention Program, and Executive Director, Clinical Services, Austin Health) and Kym Scanlon (Assistant Director, Chronic Care Program, NSW Health) presented figures showing encouraging reductions in hospital admissions for chronic heart failure since the commencement of statewide chronic care programs, such as the Victorian Hospital Admission Risk Prevention Program and the NSW Chronic and Complex Care Program.7,8 Clearly, more patients need to access these programs, with only an estimated 15% of eligible patients enrolled in Victoria (Andrea Driscoll, Deakin University). NSW Health is currently addressing implementation and spread of issues through a statewide chronic care collaboration that focuses on heart failure and chronic obstructive pulmonary disease. The change principles of the collaboration are based on the key elements of Wagner’s chronic care model, as well as policy components from the World Health Organization’s Innovative Care for Chronic Conditions Framework.9 Conclusion and the way forwardIn the concluding plenary session, Didsbury and Wagner suggested strategies that would facilitate implementation of the chronic care model in Australia. They emphasised the need to reward care planning, support efforts to encourage practice system change, and make patients a part of the planning. Using the patient journey as a framework, Geoffrey Tofler presented a matrix of key strategies and interventions that patients, clinicians and governments should consider to improve outcomes and quality of life for patients with heart failure (Box 2). The matrix indicates areas where best-practice models of care are known, such as cardiac nurse specialists for post-discharge heart failure patients, and areas where more research is needed, such as the best use of practice nurses in chronic diseases. Finally, the matrix suggests areas where enhanced government support is needed (such as in creating mechanisms for funding comprehensive care programs and in further funding for practice nurses). The range of participants at the forum reinforced the broad approach needed to improve outcomes in heart failure. Furthermore, strategies adopted successfully with heart failure could have major effects when extrapolated to other chronic conditions. The forum presentations and a more detailed report are available on the National Institute of Clinical Studies website (www.nicsl.com.au). 1 The chronic care model Source: Ed Wagner keynote address, NICS Heart Failure Forum 2004. Available at www.nicsl.com.au. For more information on the chronic care model, see reference 3. 2 Matrix of key strategies and interventions for a patient with heart failure Stage Prevention Early stage Acute exacerbation Ongoing care Palliative care Issues Identification of high-risk patients Recognition of early signs and symptoms, when and whom to refer for echocardiography Use and availability of echocardiography, particularly in rural areas Use of BNP in primary care to be further defined In-hospital initiation of appropriate therapy and discharge to community with management plan, including dose titration schedules Comorbidities, diagnostic issues, systematic patient education and support Need research on the education of practice nurses in chronic care management and effectiveness in improving patient outcomes Changing roles in general practice Need research on access to palliative care services and how to extend these to patients with heart failure Model Prevention and management of coronary artery disease and hypertension Consumer Education (NICS Online directory of quality information for patients with heart failure) Appropriate use of echocardiography in diagnosis and assessment of heart failure in primary care (NICS education module in preparation) Clinician-led quality improvement programs Heart failure nurse-led, home-based management programs (Alternatives include hospital-based rehabilitation, heart failure clinics) Chronic care management model Study and implement self-management models Targeted interventions aimed at implementing best practice management of heart failure in primary care (NICS, NPS and NHFA joint heart failure program) Need research on appropriate palliative care model and extrapolation of palliative care and nursing principles Consumer role Awareness of risk factors (SNAP) Awareness of early symptoms and precipitants, especially in high risk individuals Working in partnership with healthcare professionals Access to self-management education and support, particularly post-discharge Self-management education and support, ongoing monitoring, adherence to treatment Heart Failure Action plan Consider advance directives Access to self-management and support Provider role Identification and treatment of high-risk patients by GPs, cardiologists, general physicians Assessment of patients with early signs and symptoms by GPs Referrals to cardiologists or general physicians, where appropriate Emergency physicians, cardiologists, general physicians, geriatricians, cardiac nurses, hospital pharmacists GPs, practice nurses with training in chronic care and support from cardiac nurses, allied health, community nurses and pharmacists GPs, community nurses, palliative care teams Government role Heart failure health promotion campaign, and systems in place to support this Access to echocardiography, access to cardiologists Need heart failure prevalence study and minimum heart failure dataset Need initiatives for improved outcomes for cardiovascular disease in primary care Ongoing resourcing for cardiac nurse role in acute settings and post-discharge (state) Testing and implementation of chronic care model in general practice and system redesign issues (Commonwealth) Mechanism for funding comprehensive care programs More practice nurses Capacity building for quality improvement Extend palliative care entitlements to patients with heart failure (eg, access to medicines, oxygen and home nursing services) BNP = Brain natriuretic peptide. NICS = National Institute of Clinical Studies. NPS = National Prescribing Service. NHFA = National Heart Foundation of Australia. SNAP = Smoking, Nutrition, Alcohol, Physical activity.

Susan M Phillips DPhil · Janice M Davies PhD · Geoffrey H Tofler MB BS, MD

Raised plasma homocysteine (tHcy) concentrations are caused by genetic mutations, vitamin deficiencies, renal and other diseases, numerous drugs, and increasing age. Raised tHcy concentrations are associated with laboratory evidence of atherogenesis (eg, endothelial dysfunction) and thrombosis, and epidemiological evidence of an increased risk of atherothrombotic vascular disease. An association between raised tHcy concentration and an increased risk of atherothrombosis is independent of other vascular risk factors, strong, dose-related and biologically plausible, but has not been proven to be causal in randomised controlled trials. A recent trial identified no significant benefit from lowering tHcy concentration by folic-acid-based multivitamin therapy among 3680 patients with recent ischaemic stroke, but did not reliably exclude a modest but important reduction in the relative risk of stroke of up to 20%; a difference of only 2 mmol/L in tHcy concentration between the two treatment groups was probably due to widespread vitamin use and fortification of grains and staple foods with folate in North America. There is currently insufficient evidence to recommend routine screening and treatment of high tHcy concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MSc, FRACP, FRCPA · Wai Khoon Ho MB ChB, FRACP, FRCPA · Frank M van Bockxmeer PhD, FAHA

Cardiovascular disease is the leading cause of morbidity and mortality in Australia. It is therefore important that all medical practitioners are familiar with the well documented risk factors for cardiovascular disease, as well as the outcome benefits of pharmacological and other interventions. The large and ever-increasing body of clinical evidence, the range of patient groups at risk and the plethora of recommended interventions all make it increasingly difficult for busy doctors to adopt an integrated approach to prevention of vascular events. While absolute risk calculators, such as the Framingham Heart Study Prediction Score Sheets (www.nhlbi.nih.gov/about/framingham/riskabs.htm) or the New Zealand Cardiovascular Risk Factor Calculator (www.racp.edu.au/bp/resources/EBM_cardio.pdf), enable doctors to assign overall risk, guidelines for management are usually focused on single interventions. Moreover, the continual emergence of new data on vascular risk management redefines risk categories and approaches to risk management. Prevention of cardiovascular disease: an evidence-based clinical aid was developed by a multidisciplinary group of physicians to address this issue and was first published by the MJA in July 2003. We have revised and updated our evaluation of current best practice based on a rigorous analysis of available published evidence to March 2004, and formulated a concise and up-to-date guide for the prevention of cardiovascular disease. This consensus of opinions is summarised in this document (see Clinical aid, page F12) and provided as a single-page chart for use in clinical practice as a desktop reference. Patients were classified as being either at high or low risk of cardiovascular events (Box 1). It is widely considered that high-risk patients are those with clinically evident vascular disease, renal disease, diabetes or other risk factors conferring an annual risk of a future event of 2%–3% or greater. Risk can be calculated using an absolute risk-factor calculator (see above). The major interventions considered were: lifestyle changes; cessation of smoking; and treatment of hypertension and dyslipidaemia. Where new indications for treatment have been demonstrated in particular circumstances for a single product, this product is shown; otherwise, the class of agents is presented. We considered the results of recent trials that will potentially have a major impact on the management of high-risk patients. Such trials include the HOPE study,1 the PROGRESS study2 and the Heart Protection Study.3 Furthermore, the recognition that proteinuria imparts substantial risk warranted the inclusion of specific advice for the population with this risk factor. Although the importance of homocysteine, Lp(a) and fibrinogen as cardiovascular risk factors was recognised, the infrequent measurement of these parameters in usual practice, together with the lack of proven interventions, justifies their omission from this review. We anticipate further updates and revisions to the aid to maintain its currency in the context of a rapidly expanding cardiovascular evidence base. The management recommendations of this “living” document will continually evolve as new evidence is published. It should be noted that this clinical aid applies to the long-term management of cardiovascular risk in general practice or community-based physicians’ practice. It does not cover the medical management of acute coronary syndromes or heart failure. Glossary of abbreviations ACE inhibitor – angiotensin-converting enzyme inhibitor AIIRA – angiotensin II receptor antagonist AMI – acute myocardial infarction CCF – congestive cardiac failure CHD – coronary heart disease HDL cholesterol – high-density lipoprotein cholesterol LDL cholesterol – low-density lipoprotein cholesterol RCT – randomised controlled trial TIA – transient ischaemic attack Recommendations for all patientsHealthy lifestyleAdvice concerning the benefits of smoking cessation, physical activity and healthy dietary choices should be given at a population and individual level. These measures are considered as first-line in any management decisions. a) Cessation of smokingThere is extensive evidence that smoking is strongly related to mortality, largely because of an increased risk of CHD and stroke.4 Furthermore, smoking cessation has been shown to decrease this risk in patients with and without established CHD.5 In patients with peripheral vascular disease or stroke, smoking cessation is associated with improved exercise tolerance and survival, and decreased rates of limb amputation and recurrent stroke.5 b) ExerciseWhile there is limited evidence from RCTs of the value of exercise in primary prevention of cardiovascular disease, there is strong observational evidence that moderate, regular physical activity reduces the risk of both CHD6 and stroke,7 and that the risk is increased in people with a sedentary lifestyle.8 For secondary prevention after AMI, two meta-analyses of exercise-based rehabilitation in up to 14 RCTs have shown reductions in mortality of between 20% and 25% (absolute risk reduction [ARR], 3.1%) at 3-year follow-up, although many of the trials allowed other risk-factor intervention as well.9,10 While these data must be interpreted with caution, prescribing a moderate degree of regular physical exercise is consistent with published evidence. c) DietCohort studies have shown that eating fruit and vegetables reduces the risk of heart attack and stroke.11 One RCT showed that a Mediterranean diet decreased mortality by 30% at 27 months after AMI (ARR, 4.0%).12 In addition, a modest intake of fish (as little as 35 g daily) appears to decrease the relative risk of AMI.13 Following general advice to decrease the intake of saturated fats and cholesterol and increase the intake of polyunsaturated fats favourably affects serum lipid levels and decreases the likelihood of CHD.14 Finally, weight maintenance education should be part of routine advice for the general population, but is particularly important in patients at increased risk of cardiovascular events. d) StressRecently, an Expert Working Group of the National Heart Foundation of Australia undertook a review of the evidence relating to major psychosocial risk factors to assess whether these influenced the development of CHD and acute coronary events.15 They concluded that there was “no strong or consistent evidence for a causal association between chronic life events, work-related stressors (job control, demands and strain), type A behaviour patterns, hostility, anxiety disorders or panic attacks and CHD”.15 However, there was strong and consistent evidence of an independent and causal association between depression, social isolation and the prognosis of CHD and, importantly, the impact of these was of a similar order to conventional risk factors such as smoking.15 It is therefore crucial that these psychosocial factors are considered during individual CHD risk assessments. Recommendations for patients with established vascular disease1. Normotensive patients with a history of cardiovascular diseaseThe HOPE,1 PROGRESS2 and, more recently, EUROPA studies16 have examined the effects of preventive treatment with ACE inhibitors in normotensive high-risk patients. In the HOPE study, patients with CHD, peripheral vascular disease, stroke, or diabetes (types 1 or 2) and an additional risk factor were randomly allocated to receive ramipril 10 mg daily or placebo. Patients were included irrespective of a history of hypertension, but those with blood pressure greater than 140/90 mmHg or with a specific indication for treatment with an ACE inhibitor (eg, CCF) were excluded. The 3/1 mmHg lower blood pressure in the ramipril group at the end of the study was unlikely to explain the highly significant 22% reduction in the combined endpoint of cardiovascular death, stroke or heart attack (cardiovascular death [26% reduction; ARR, 2.0%], stroke [32% reduction; ARR, 1.5%], heart attack [20% reduction; ARR, 2.2%]; P < 0.05) or the 17% decrease in total mortality (P < 0.05).1 In the PROGRESS study,2 patients with a previous history of stroke or TIA were randomly allocated to perindopril 4 mg ± indapamide 2.5 mg versus placebo, whether there was a history of hypertension or not. When given together this combination reduced the risk of recurrent stroke (fatal or non-fatal) and major vascular events in both normotensive and hypertensive patients with this background.2 There was also a significant reduction in major coronary events (26%) and the development of heart failure (26%) in these patients with underlying cerebrovascular disease.17 The magnitude of blood pressure reduction in the active treatment group was greater in the PROGRESS study (9/4 mmHg) than in the HOPE study (3/1 mmHg), making it less clear as to how much of the benefit seen in the PROGRESS study was independent of blood pressure reduction alone. The recently published EUROPA study16 looked at patients with known ischaemic heart disease, and participants were randomly allocated to receive perindopril 8 mg or placebo, independent of whether or not they had a history of hypertension. At 5 years, there was a significant 20% reduction in cardiovascular mortality, infarction and cardiac arrest in patients who received perindopril, with a blood pressure difference of 5/2 mmHg between the groups. It appears that, in patients with a history of CHD or cerebrovascular disease, treatment with a high dose ramipril- or perindopril-based regimen will improve outcomes whether or not there is a history of hypertension, and that at least some of these benefits are independent of blood pressure reduction alone. In the immediate post-infarct management of normotensive patients, a mortality benefit in the short term has also been demonstrated with β-blockers18 and ACE inhibitors (particularly in patients with associated heart failure),19 with less robust evidence for calcium channel blockers, verapamil and diltiazem.20-22 2. Patients with elevated blood pressure and a history of cardiovascular diseaseWhile epidemiological studies have established that raised blood pressure is a major risk factor for cardiovascular events in patients with a history of AMI,23 until recently there has been no systematic review or RCT that specifically examines blood pressure reduction in patients with established CHD, nor in those with peripheral vascular disease; however, the results of the HOPE, PROGRESS and EUROPA studies are applicable to patients with hypertension. In our recommendations, and those of both the JNC-7 Report24 and the National Heart Foundation,25 the benefits of blood pressure lowering in patients with CHD have been extrapolated mostly from primary prevention trials and from studies of patients after AMI.1,18-22 Evidence of event reduction exists for patients taking calcium channel blockers,20-22,26-29 diuretics and β-blockers,29-35 and ACE inhibitors.1,28,35 In patients with elevated blood pressure and a history of stroke or TIA, the evidence is strongest for the use of ACE inhibitors (ramipril 10 mg; and perindopril 4 mg when given with indapamide 2.5 mg),1,2 diuretics and β-blockers.34-38 More recently, the INVEST study39 examined patients with hypertension and known ischaemic heart disease. This study found that event rates were similar in both subjects taking a verapamil-based regimen and in those receiving atenolol-based therapy. However, to achieve target blood pressures, most patients in both study groups were taking combination therapy that also included an ACE inhibitor and thiazide diuretic. As over 50% of patients in the ALLHAT study38 had a history of atherosclerotic cardiovascular disease, the result of this study should be considered when blood pressure lowering is contemplated for such patients.38 Specifically, the results of treatment with ACE inhibitors, diuretics or calcium channel blockers were comparable. It should be noted, however, that there was an increased rate of development of diabetes mellitus in the thiazide diuretic treatment arm. In view of the impact of diabetes on cardiovascular event rates, this finding may have implications for cardiovascular disease beyond the 5-year treatment period covered by the trial. 3. Patients with dyslipidaemia and a history of cardiovascular diseaseThere is strong RCT evidence that lowering cholesterol levels decreases cardiovascular mortality and morbidity in patients who have been diagnosed with an acute coronary syndrome or myocardial infarction,40 even if cholesterol levels are normal.3,41,42 The most substantial data are from studies of simvastatin and pravastatin,3,40-42 but, recently, results of the PROVE-IT study43 suggest that intensive lipid lowering with atorvastatin 80 mg improves outcomes more than moderate lipid lowering in patients with acute coronary syndromes and cholesterol levels less than 6.2 mmol/L.43 The Heart Protection Study3 provides the most complete information of the benefits of lowering cholesterol level in a wide range of circumstances. Both men and women with total cholesterol levels greater than 3.5 mmol/L and with a history of cardiovascular disease (including those with a history of coronary disease, cerebrovascular disease, or peripheral vascular disease) achieved a significant reduction in major vascular events (P < 0.001) irrespective of the starting cholesterol level. In men with low levels of HDL cholesterol and a history of CHD, gemfibrozil significantly reduced the risk of major cardiovascular events, in the absence of an effect on LDL cholesterol level.44 In patients with diabetes and CHD, the data are strongest for the use of statins,3,40-42 but, again, in patients with low levels of HDL cholesterol gemfibrozil is efficacious.44 To date, this evidence has been derived from subgroup analyses. In RCTs, it has been shown that both pravastatin and simvastatin reduce the incidence of stroke in patients with CHD,3,41,42,45 but in those without CHD the evidence is strongest for simvastatin.3 There are no “head-to-head” outcome studies of statins versus fibrates. Recommendations for patients with diabetes without known cardiovascular disease1. Patients with diabetes and “normal” blood pressureIn patients with diabetes, “normal” blood pressure is arbitrarily defined as being less than 130/85 mmHg and “ideal” blood pressure as less than 120/80 mmHg.25 As the HOPE study1 only included patients with diabetes if they had at least one cardiovascular risk factor, treatment of low-risk patients with diabetes (ie, those who have no additional cardiovascular risk factors) with an ACE inhibitor to prevent future CHD events is not supported by current data. Observation with repeated measurement of blood pressure at least annually is recommended.25,46 2. Patients with diabetes and elevated blood pressureA systematic review of RCTs has shown that ACE inhibitors, diuretics, calcium channel blockers and β-blockers are all effective in primary prevention of cardiovascular events in patients with diabetes and hypertension.47 There is no clear evidence that any of these classes is more effective than another in event reduction,26,28 and currently drugs of all of these classes are recommended to treat blood pressure in patients with diabetes.25 Despite this, an apparent greater reduction in major cardiovascular events (including heart failure) occurring with ACE inhibitors, compared with some calcium channel blockers,48-50 has led us to list calcium channel blockers as second-line therapy. In addition to reducing cardiovascular events, ACE inhibitors have a major role in renal protection in patients with type 1 diabetes and hypertension.51 Similar protection has recently been shown with the AIIRAs irbesartan52,53 and losartan,54 including patients with type 2 diabetes and left ventricular hypertrophy.55 3. Lowering cholesterol level in patients with diabetesIn the Heart Protection Study,3,56 patients with diabetes with a total cholesterol level greater than 3.5 mmol/L had significantly fewer major vascular events (P < 0.0001) when taking simvastatin 40 mg, whether or not they had a prior history of CHD. To date, this is the largest intervention trial of statin therapy in patients with diabetes and thus should be considered the definitive trial. These data support the use of a statin for both primary and secondary prevention of major vascular events in patients with diabetes. Furthermore, three large primary prevention RCTs using lovastatin,57 gemfibrozil58 and bezafibrate59 have each shown a benefit in preventing cardiovascular events. Thus, a predominant elevation of total or LDL cholesterol levels indicates a statin is appropriate initial therapy, whereas a fibrate could be an appropriate choice in patients with low levels of HDL cholesterol and raised triglyceride levels. When treating combined hyperlipidaemia, both classes of drug may be required, but there are no outcome data from using this approach and practitioners should exercise caution in prescribing this combination. Definitive trials on lipid management in patients with diabetes (eg, the FIELD study60) are still to be published. 4. Cardiovascular prevention with other therapiesAs the HOPE study included patients with diabetes and dyslipidaemia (total cholesterol level > 5.2 mmol/L and HDL cholesterol level 0.9 mmol/L),61 the use of ramipril in addition to other therapies should be advocated in diabetic patients with dyslipidaemia or other cardiovascular risk factors. Recommendations for patients with non-diabetic renal disease1. Patients with non-diabetic renal disease and “normal” blood pressureRenal insufficiency is a well described predictor of cardiovascular outcomes.62 Hypertension in patients with renal disease is defined as blood pressure greater than 130/85 mmHg,25 although observational studies suggest that even a lower blood pressure confers an increased risk. Despite this, there is no RCT of antihypertensive therapy showing treatment benefit if blood pressure is below this threshold. Ongoing observation with repeated measurement of blood pressure every 6 months is currently recommended for normotensive patients with non-diabetic renal disease.24,25,46 2. Patients with non-diabetic renal disease and hypertensionThe benefits of treating hypertension in patients with established renal disease have largely been studied with surrogate endpoints, and the effects of lowering blood pressure on cardiovascular outcomes have not been specifically assessed. Nevertheless, patients with renal dysfunction are at high risk of CHD and it is reasonable to extrapolate from this that aggressive blood pressure lowering will confer a substantial benefit.25 Published data support the use of ACE inhibitors as first-line treatment for hypertension, with greater demonstrated efficacy in reducing proteinuria than calcium channel blockers.51 Further, in a meta-analysis of a number of clinical trials, ACE inhibitors were more effective than other agents in delaying the development of end-stage renal disease; however, it could not be determined whether this was due to the lower blood pressure achieved with ACE inhibitors or to effects independent of blood pressure.63 β-Blockers and diuretics are also recommended.24,25 If calcium channel blockers are used they should be considered as second-line therapy after ACE inhibitors.51 More recent information in this patient group has been derived from the CATS64 and COOPERATE65 studies. The CATS study showed that, although renal function deteriorated markedly after a first AMI, it was significantly preserved by taking the ACE inhibitor captopril. Patients after a first anterior-wall AMI were allocated at random to receive captopril (up to 75 mg daily) or placebo, after completion of a streptokinase infusion. Renal function determined by calculating glomerular filtration rate was found to decline by 5.5 mL/min within 1 year versus only 0.5 mL/min in the captopril group (P < 0.05). The beneficial effects of captopril were most pronounced in patients with the most compromised renal function at baseline. The COOPERATE study65 aimed to assess the effects of ACE inhibitor and AIIRA therapy, both in combination as well as monotherapy at maximal dose. Participants were randomly assigned to receive losartan 100 mg daily or trandolapril 3 mg daily, or a combination of both drugs at equivalent doses. Survival analyses were done to compare the effects of each regimen on the primary combined endpoint of time to doubling of serum creatinine concentration or end-stage renal disease on an intention-to-treat basis. Eleven per cent of patients taking the combination treatment reached the combined primary endpoint, compared with 23% of patients taking trandolapril alone (hazard ratio, 0.38; 95% CI, 0.18–0.63; P = 0.018) and 23% of patients taking losartan alone (hazard ratio, 0.40; 95% CI, 0.17–0.69; P = 0.016). Combination treatment was found to safely retard the progression of non-diabetic renal disease compared with monotherapy; however, as some patients taking combined therapy reached the combined endpoint, further research on strategies for complete management of progressive non-diabetic renal disease is needed. 3. Lowering cholesterol level in patients with non-diabetic renal diseaseSpecific trials of lipid-lowering therapy have not been conducted in patients with non-diabetic renal disease. Thresholds for intervention have been derived by consensus and recommendations for the choice of agents have been based on the lipid-lowering characteristics of specific therapies. The approach for other high-risk patientsOver the past decade, it has been recommended that the intensity of risk-factor management be governed by a patient’s absolute risk of a CHD event. However, patients with mild levels of multiple risk factors may be at high risk because of the exponential additive contribution of each risk factor,66 whereas other patients may have an overall low risk even if they have one markedly abnormal risk factor (Box 1). 1. High-risk patients with raised blood pressureA number of systematic reviews have shown a reduction in total mortality, cardiovascular death, stroke, major coronary events and CCF in patients taking β-blockers, diuretics, ACE inhibitors or calcium channel blockers.25,62,67 One unblinded RCT in 6600 people aged 70–84 years, comparing diuretics and/or β-blockers versus calcium channel blockers versus ACE inhibitors, showed no significant difference in blood pressure control or cardiovascular morbidity and mortality.68 The ALLHAT study, involving hypertensive patients with at least one other CHD risk factor, supports these findings.38,69 When the primary outcome was considered (fatal CHD or non-fatal AMI), diuretic-based therapy (chlorthalidone) was of similar efficacy to either therapy with a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril). In fact, patients taking amlodipine had an increased risk of CCF (relative risk, 1.38; 95% CI, 1.25–1.52) and patients taking lisinopril had a higher risk of combined cardiovascular disease, stroke and CCF.38 As amlodipine is a dihydropyridine calcium channel blocker, it may not be possible to extrapolate these results to the non-dihydropyridine calcium channel blockers.69 2. Lowering cholesterol level in patients at high risk of a cardiovascular eventUntil recently, there was no evidence that lowering cholesterol level reduces total mortality in non-diabetic patients without cardiovascular disease, although systematic reviews and RCTs had shown that cholesterol reduction improves cardiovascular outcomes in high-risk populations.3,57,70-72 The benefit is related to baseline risk and extent of cholesterol reduction rather than initial cholesterol level (within the range studied). The lipid-lowering arm of the ASCOT study73 demonstrated the benefits of lipid reduction for hypertensive patients with multiple cardiovascular risk factors. ASCOT examined 10 305 patients with hypertension and at least three other cardiovascular risk factors (excluding previous AMI or current angina) who had non-fasting cholesterol levels less than 6.5 mmol/L. Treatment with atorvastatin 10 mg conferred a 36% reduction in fatal CHD and non-fatal AMI compared with placebo (P = 0.0005). The benefits of lipid reduction were also evident among non-diabetic patients. A total cholesterol level greater than 5 mmol/L is the current recommended threshold for treatment in patients with associated risk factors or vascular disease.74 The approach for patients at low risk of a cardiovascular eventPatients who are not in any of the above categories are at low risk of a cardiovascular event. There is a more liberal threshold for intervention in this group in the knowledge that the treatment benefits will be smaller, but the recommendations for choice of therapy to lower blood pressure and lipid levels are identical to those in higher-risk patients. 1. Blood pressure managementWe routinely adopt a more proactive approach for monitoring blood pressure than the current guidelines, which advocate that low-risk patients whose blood pressure is considered normal by current criteria should have blood pressure measurements either every 5 years (age < 60 years) or every 1–2 years (age > 60 years).25,67 Current clinical practice would also be at variance with the guideline recommendations that drug therapy and lifestyle modification for hypertension should only be introduced in patients under 60 years if their systolic blood pressure is greater than 180 mmHg or diastolic blood pressure greater than 100 mmHg,25,67 or in those over 60 years whose systolic blood pressure is greater than 160 mmHg.27,29 Despite our personal views, we have included the current published recommendations.25 In the ANBP-2 Study,75 6083 elderly subjects aged 65–84 years with hypertension were treated with either ACE inhibitors or diuretics and compared. Although a similar number of strokes occurred in each group, ACE inhibitor therapy was associated with better cardiovascular outcomes, particularly in men.75 2. Lipid managementPatients with normal lipid levels should be assessed every 5 years until middle age and then every 1–2 years. In the absence of other risk factors triggering a lower threshold for treatment, lipid-lowering therapy with a statin should be commenced for patients with predominant hypercholesterolaemia (total cholesterol > 8.0 mmol/L or total cholesterol : HDL cholesterol ratio > 8.0),76 or with a fibrate for patients with low HDL cholesterol and high triglyceride levels.74 (At present, the reimbursement criteria of the Pharmaceutical Benefits Schedule are at variance with National Heart Foundation guidelines). The approach for patients with macro- or microalbuminuria associated with diabetes or hypertensionThe finding of microalbuminuria (urinary albumin excretion 20–200 μg/min) or macroalbuminuria (urinary albumin excretion > 200 μg/min) should prompt a search for the presence of diabetes, hypertension or renal disease. If diabetes is present, the use of ramipril is appropriate for cardiovascular risk reduction.1,61 Furthermore, there is good evidence to support the use of ACE inhibitors for renal risk reduction in normotensive patients with diabetes (type 1 or type 2) and microalbuminuria1,77 and hypertensive patients with type 2 diabetes,51 and the use of AIIRAs (irbesartan and losartan) in patients with type 2 diabetes.52-54 Other interventions1. Antiplatelet therapies (aspirin, dipyridamole or clopidogrel)Aspirin (75–150 mg/day) has been shown to have significant benefit for patients at high risk of cardiovascular disease, particularly in secondary prevention,78,79 although blood pressure should be tightly controlled to minimise the risk of haemorrhagic stroke.80-82 It must be recognised, however, that the benefits of aspirin are not clear in older patients (> 70 years) with no previous cardiovascular events who, primarily due to age, remain at high risk of cardiovascular disease. This is highlighted by the recent FDA decision not to list primary prevention of cerebrovascular disease as an indication for aspirin in the elderly and to strongly support proposals for the conduct of such trials. The risks associated with gastrointestinal and cerebral bleeding in older patients may offset any cardiovascular protection benefits. The American Diabetes Association recommends the use of aspirin for patients with diabetes over the age of 30 years,83 but there is no evidence of benefit in primary prevention in low-risk subjects.80 Alternative or additional antithrombotic therapies such as clopidogrel or dipyridamole (stroke or TIA only) may be required if aspirin is not tolerated or the patient experiences recurrent cardiovascular events while taking aspirin.84-87 It is beyond the scope of this review of cardiovascular prevention measures to focus on the management of acute coronary syndromes. However, it is important to highlight the results of a recent trial using combination antiplatelet therapy in patients with acute coronary syndromes: initiating therapy during the acute management phase in hospital was shown to have benefits up to 1 year after the initial presentation. The CURE study88 showed that patients with acute coronary syndromes who were given a loading dose of 300 mg of clopidogrel followed by ongoing treatment with 75 mg daily for 9 months, in addition to their usual therapy (including aspirin), had a 20% reduction in the combined endpoint of cardiovascular death, AMI, and stroke (ARR, 2.1%).89 Thus, many patients who leave hospital after an admission with unstable angina or non-ST elevation myocardial infarction will be receiving clopidogrel in addition to aspirin as combined antiplatelet therapy for atherothrombosis, which should be continued as long-term therapy. The CREDO study showed a 27% relative risk reduction (ARR, 3.0%) in the combined endpoint of death, AMI and stroke at 1 year with the use of clopidogrel added to conventional therapy (including aspirin) after placement of a coronary stent.89 Once again, early treatment translates into long-term preventive therapy, and thus a case can be made for the use of combination antiplatelet therapy (aspirin and clopidogrel) for preventing ischaemic events in appropriate patients. Definitive long-term trials of this combination to prevent events in patients with cardiovascular disease (but who have not presented with an acute coronary syndrome), or to avoid the need for coronary artery stenting, are currently under way. 2. AnticoagulationLong-term anticoagulation to reduce thromboembolism may be required for patients with paroxysmal or chronic atrial fibrillation, proteinuria greater than 3 g/day, and those with a history of extensive anterior infarction or severe CCF.90,91 ConclusionPrevention of cardiovascular disease: an evidence-based clinical aid 2004 is based on a review of current evidence and practice, incorporating data from RCTs, as well as recommendations from local and international guidelines. This clinical aid consolidates current evidence and recommendations into a single source and provides a reference tool for the optimal treatment of “at-risk” patients to prevent vascular events and improve clinical outcomes. 1 Categories of patients based on future risk of a cardiovascular event High-risk patients are those with: Clinically evident coronary heart disease (prior acute myocardial infarction, angina, or history of a revascularisation procedure) Clinically evident vascular disease (cerebrovascular or peripheral vascular disease) Diabetes Renal disease A risk of a future vascular event ≥ 2%–3% per year, based on an aggregate of unfavourable risk characteristics* Low-risk patients are those with: A risk of a future vascular event < 2%–3% per year* * Determined using a calculation of the 5-year risk of any cardiovascular event and death, from a validated absolute-risk calculator such as the Framingham Heart Study Prediction Score Sheets or, in the case of type 2 diabetes, the UK Prospective Diabetes Study risk calculator (www.dtu.ox.ac.uk/index.html?maindoc=/riskengine/). 2 Competing interests Name Consultant fees Honoraria/fees for service Advisory/Steering Committee fees Investigator-initiated research grants Travel assistance Dr John V Amarena BMS, Boehringer Ingelheim, Novartis, Sanofi Abbott, Aventis, BMS, MSD, Servier, Solvay Aventis, BMS, Sanofi Boehringer Ingelheim, Pfizer, Sanofi Dr John F Beltame Alphapharm, Aventis, Bayer, BMS, MSD, Pfizer, Roche, Sanofi, Servier Aventis, BMS, Pfizer, Solvay Prof Stephen Colagiuri MSD, Novo Nordisk, Roche, Servier Member of MSD steering committee — unpaid Dr Greg W Conner Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Abbott, AZ, Aventis, Bayer, Boehringer Ingelheim, BMS, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, Servier Dr Greg R Fulcher Aventis, BMS, MSD, Novo Nordisk, Sanofi, Eli Lilly Aventis, GSK, MSD, Novo Nordisk, Sanofi, Aventis, MSD Prof Richard E Gilbert Aventis, AZ, BMS, MSD BMS AZ, Servier Prof Graeme Hankey BMS, Sanofi Aventis, BMS, MSD, Pfizer, Sanofi BMS, Pfizer, Sanofi Assoc Prof Anthony C Keech Laboratoires Fournier, MSD (contribution to department) BMS, Laboratoires Fournier, MSD Invited lectures only Prof Brian R McAvoy Aventis Prof Carol A Pollock Aventis, Sanofi, Servier BMS Prof Malcolm J West Aventis, BMS, MSD Aventis, BMS, MSD BMS, MSD BMS Aventis, BMS, MSD Abbott = Abbott Australasia; Aventis = Aventis Pharma; AZ = AstraZeneca; BMS = Bristol-Myers Squibb; GSK = GlaxoSmithKline; MSD = Merck Sharpe & Dohme/Amrad; Sanofi = Sanofi-Synthelabo

Practical Implementation Taskforce for the Prevention of Cardiovascular Disease

Cardiovascular disease is the leading cause of morbidity and mortality in Australia. It is therefore important that all medical practitioners are familiar with the well documented risk factors for cardiovascular disease, as well as the outcome benefits of pharmacological and other interventions. The large and ever-increasing body of clinical evidence, the range of patient groups at risk and the plethora of recommended interventions all make it ...

Practical Implementation Taskforce for the Prevention of Cardiovascular Disease

The prevalence of peripheral arterial disease (PAD) in people aged over 55 years is 10%–25% and increases with age; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Patients with PAD alone have the same relative risk of death from cardiovascular causes as those with coronary or cerebrovascular disease, and are four times more likely to die within 10 years than patients without the disease. The ankle–brachial pressure index (ABPI) is a simple, non-invasive bedside tool for diagnosing PAD — an ABPI less than 0.9 is considered diagnostic of PAD. About half of patients with PAD (defined by an abnormal ABPI) have symptomatic coronary or cerebral vascular disease. The ABPI is an independent predictor of coronary and cerebrovascular morbidity and mortality. Patients with PAD require medical management to prevent future coronary and cerebral vascular events. There are currently insufficient data to recommend routine population screening for asymptomatic PAD using the ABPI.

Paul E Norman DS, FRACS · John W Eikelboom MB BS, FRACP · Graeme J Hankey MD, FRACP

Clive D Hadfield Gastroenterologist, 30 Megan Street, Cairns, QLD 4870. chadfieldATaustarnet.com.au To the Editor: In their recent study, Scott and colleagues demonstrated benefit from a program to standardise clinical management of cardiac conditions in Queensland hospitals.1 They found differences in the effect on “low-intensity intervention” hospitals compared with “high-intensity intervention” hospitals. The former were, by and large, district-type hospitals and the latter tertiary hospitals. The study found that about 50% more patients in the larger hospitals had assessments of left ventricular function. Three times as many patients in the larger hospitals accessed rehabilitation. Nearly three times as many patients in the smaller hospitals were readmitted with a diagnosis of acute coronary syndrome within 30 days, perhaps a surrogate for angiography rates, which were not reported differentially. It may be that the most urgent intervention required is “high-intensity” funding of district hospitals, so that they can achieve rates of echocardiography, rehabilitation and coronary angiography approaching those of tertiary hospitals. This intervention would need no further justification than that the population served by the district hospitals has paid its share for these treatments. Let us hope that the remaining comparative outcome data are published.

Clive D Hadfield

Ian A Scott,* Irene C Darwin,† Kathy H Harvey,‡ Andy B Duke,§ Nicholas D Buckmaster,¶ John Atherton,** Hazel E Harden,†† Michael Ward,‡‡ for the CHI Cardiac Collaborative * Director of Internal Medicine, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102; † Program Manager, ‡ Project Manager, § Senior Analyst, Collaborative for Healthcare Improvement, Queensland Health; ¶ Director of Medicine, Caboolture Hospital; ** Director of Cardiology, Royal Brisbane Hospital; †† Program Manager, Integrating Strategy and Performance, Queensland Health; ‡‡ Program Director, Queensland Health Skills Development Centre, Royal Brisbane Hospital. ian_scottAThealth.qld.gov.au In reply: We agree with Hadfield that optimising cardiac care may require extra resources targeted at increasing access of patients in regional Queensland to specific interventions, such as coronary angiography, cardiac rehabilitation and echocardiography, in addition to the quality-improvement strategies used within our collaborative. We contend that both approaches are necessary, and that the magnitude of improvement achieved by either will depend on the intensity with which they are applied. Indeed, the “high-intensity” quality-improvement hospitals in our study were defined on the basis of more funding being made available to undertake quality-improvement activities at those sites. We concede that some of the differences in quality indicators between “high-intensity” and “low-intensity” quality-improvement hospitals may be attributable to inequities in capital expenditure on service delivery that we did not measure. However, some of the differences may have also arisen from variation in systems for identifying and referring those patients who have most to gain from receiving the care targeted by our collaborative.

Ian A Scott · Irene C Darwin · Kathy H Harvey · Andy B Duke · Nicholas D Buckmaster · John Atherton · Hazel E Harden · Michael Ward

Objective: To determine the incidence of congenital heart defects (CHD) in Aboriginal and non-Aboriginal infants in Central Australia and to compare this with the incidence elsewhere in Australia.Design and setting: Data on cases were obtained from patient records of the Alice Springs Hospital, Central Australia, the sole referral centre for paediatric and initial cardiac diagnostic services for the region.Participants: Patients with CHD proven by echocardiography reported between 1 January 1993 and 30 June 2000.Main outcome measures: Incidence of CHD using all live births in Central Australia as the denominator.Results: 108 patients with CHD were detected among 6156 live births (incidence, 17.5 per 1000; 95% CI, 14.9–21.7 per 1000); 57 of 2991 were Aboriginal (19.0 per 1000; 95% CI, 14.4–24.6 per 1000) and 51 of 3165 were non-Aboriginal (16.1 per 1000; 95% CI, 12.0–21.1 per 1000). The difference between the two groups was not statistically significant (relative risk, 1.18; 95% CI, 0.81–1.72). CHD incidence in Central Australia was significantly higher than that reported for other parts of Australia (4.3 per 1000 live births in New South Wales and the Australian Capital Territory, 1981–1984; 7.65 and 12 per 1000 total births in Western Australia, 1980–1989, and South Australia, 1993–2000, respectively).Conclusions: The high rates of CHD in Central Australia may partly reflect the high utilisation of echocardiography for assessing minor lesions. However, the incidence of both major and minor types of CHD was significantly higher than previously reported from other regions of Australia. The role of socioenvironmental factors in this high incidence should be explored.

Srinivas Bolisetty FRACP · Ameet Daftary MD · Dan Ewald FAFPHM · Brodie Knight FRACP · Gavin Wheaton FRACP

To the Editor: We report a case in which routine use of transesophageal echocardiography (TOE) during cardiac surgery almost certainly prevented a patient’s death. This is important, as the Australian Government Department of Health and Ageing has recently decided that TOE during routine coronary artery cardiac surgery should not attract a Medicare benefit as there is no Level 1 or 2 evidence of its efficacy.1 A 65-year-old man with critical aortic valve stenosis and severe left ventricular dysfunction, requiring an intra-aortic balloon pump, was scheduled for mechanical aortic valve replacement. He had been in atrial fibrillation intermittently, but was in sinus rhythm for the 24 hours before surgery and his heparin had been at therapeutic levels since balloon pump insertion 36 hours before. Like most cardiac anaesthetists in Australia, we routinely perform TOE during cardiac surgery. Following induction of anaesthesia, TOE examination confirmed severe aortic stenosis and poor left ventricular function, but the left atrial appendage was not specifically examined and a routine preoperative transthoracic echocardiogram had shown no other abnormalities. With the patient on cardiopulmonary bypass, the diseased valve was replaced. Before weaning the patient from bypass, a TOE examination showed a large free 2.5 × 2 cm mass in the left atrium resembling thrombus (Box [a]). The surgeon then reported having invaginated the left atrial appendage while de-airing. While the patient was still on bypass, a large organised clot was removed from the left atrium (Box [b]) — this had presumably developed sometime during the preoperative period. Subsequent separation of the patient from bypass was uneventful, and he made a good recovery. The thrombus would not have been suspected or found without the TOE, and almost certainly would have migrated from the left atrium into the left ventricle following the return of cardiac output, and would likely have precipitated a sudden cardiac arrest with acute valvular obstruction. Despite the lack of Level 1 or 2 evidence, most cardiac anaesthetists and surgeons consider TOE an invaluable diagnostic and monitoring tool, particularly for assessment of left ventricular function and filling. While TOE has not rendered the Swan–Ganz catheter obsolete, it provides similar information with fewer complications. This case is a dramatic illustration of the usefulness of TOE during cardiac surgery, but less dramatic examples occur much more frequently. The Department of Health and Ageing decision not to support TOE (except in valve repair or replacement) seems shortsighted. While we support the Department’s evidence-based approach, it would be interesting to know how many procedures listed in the Medicare Benefits Schedule would withstand the same scrutiny. Randomised trials are difficult to perform, but, at the very least, TOE has excellent peer consensus, strong anecdotal evidence and large series reviews2,3 supporting its routine use in cardiac surgery. Atrial thrombus in left atrium detected by transoesophageal echocardiography during cardiac surgery (a) Echocardiogram showing the mass. (b) The clot that was removed.

Chris J Cokis · John Faris

Cardiovascular malformations occur in up to 47% of women with Turner syndrome. Aortic dissection, a devastating and often fatal condition, occurs more frequently in women with Turner syndrome than in the general population (0.8% v 0.00001%), particularly in women with 45XO monosomy. There have been many reported cases of Stanford type A aortic dissection (involving the ascending aorta or aortic arch, with variable distal extension) in women with Turner syndrome, but type B dissections (involving only the aorta distal to the arch) are relatively uncommon. We recently successfully treated a 38-year-old woman with Turner syndrome (45XO) who had a Stanford type B thoraco-abdominal aortic dissection. A computed tomography scan (Box) demonstrated contrast within the larger true lumen of the aorta and the smaller false lumen of the dissection, separated by intima. Clinicians treating a patient with Turner syndrome should be aware of their patient’s genotype and investigate for the presence of cardiovascular malformations to help stratify the risk. It is important to remain alert to the possibility of aortic dissection in patients with Turner syndrome who complain of chest pain, abdominal pain or dyspnoea, as early detection may save a life. Ao = aorta (true lumen). D = diaphragm. Ht = heart. IVC = inferior vena cava. Lg = lung. Lr = liver. Arrow indicates false lumen of aortic dissection.

Colin I Clement MB BS, PhD · John Brereton FRACS · Phillip Clifton-Bligh FRACP

In patients hospitalised with acute coronary syndromes (ACS) and congestive heart failure (CHF), evidence suggests opportunities for improving in-hospital and after-hospital care, patient self-care, and hospital–community integration. A multidisciplinary quality improvement program was designed and instigated in Brisbane in October 2000 involving 250 clinicians at three teaching hospitals, 1080 general practitioners (GPs) from five Divisions of General Practice, 1594 patients with ACS and 904 patients with CHF. Quality improvement interventions were implemented over 17 months after a 6-month baseline period and included: clinical decision support (clinical practice guidelines, reminders, checklists, clinical pathways); educational interventions (seminars, academic detailing); regular performance feedback; patient self-management strategies; and hospital–community integration (discharge referral summaries; community pharmacist liaison; patient prompts to attend GPs). Using a before–after study design to assess program impact, significantly more program patients compared with historical controls received: ACS: Angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering agents at discharge, aspirin and β-blockers at 3 months after discharge, inpatient cardiac counselling, and referral to outpatient cardiac rehabilitation. CHF: Assessment for reversible precipitants, use of prophylaxis for deep-venous thrombosis, β-blockers at discharge, ACE inhibitors at 6 months after discharge, imaging of left ventricular function, and optimal management of blood pressure levels. Risk-adjusted mortality rates at 6 and 12 months decreased, respectively, from 9.8% to 7.4% (P = 0.06) and from 13.4% to 10.1% (P = 0.06) for patients with ACS and from 22.8% to 15.2% (P < 0.001) and from 32.8% to 22.4% (P = 0.005) for patients with CHF. Quality improvement programs that feature multifaceted interventions across the continuum of care can change clinical culture, optimise care and improve clinical outcomes.

Ian A Scott MHA, FRACP · Annabel C Hickey MMSc(Clin Epi), BAppSc(OT) · Daniela C J Sanders BPharm(Hons) · Mark A Jones BSc(Hons) · Charles P Denaro MD, FRACP · Cameron J Bennett MB BS, MBiomedE, FRACP · Alison M Mudge MB BS, FRACP · Justine M Thiele BPharm · Judy L Flores BA, MD, FRACP · Beres Wenck FRACGP · John W Bennett BMedSc, MB BS, BA(Hons), FRACGP

Towards a Safer Culture (TASC) aims to provide a safer culture in hospital departments by introducing clinical pathways for the management of patients with acute coronary syndromes or stroke. Specific clinical pathways have been implemented for patients with different levels of risk to guide the most appropriate evidence-based medical care for each patient. Pathways facilitate continuity of care across different clinical departments by identifying gaps in care, and clarifying tasks and responsibilities. A multidisciplinary and interdepartmental approach to managing patients is seen as an effective way of effecting change. A system for “point-of-care” data acquisition, a centralised database and web-based reporting enable benchmarking for participating hospitals. A comprehensive range of educational/training strategies is used to facilitate multidisciplinary teamwork and promote clinical leadership. Phase 1 of TASC was successfully piloted at four hospitals in New South Wales, Victoria and Queensland. TASC is currently being rolled out to 29 hospitals in NSW and three hospitals in Western Australia.

Catherine T Ferry BN, GradDipPubHlth · M Andrew Fitzpatrick BSc(Med), MD, FRACP · Paul W Long GradDip(CommMgt) · Christopher R Levi BSc(Med), FRACP · Roderick O Bishop BSc(Med), MPH, FACEM

Objectives: To determine the incidence rate of coronary heart disease (CHD) in Australian Aboriginal people with type 2 diabetes, and to compare the impact of diabetes on CHD risk in Aboriginal women and men.Design: Cohort study.Setting: A remote Aboriginal community in the Northern Territory.Participants: 889 Aboriginal people aged 20–74 years followed up to 31 May 2003 after baseline examination in 1992–1995.Main outcome measures: Incidence rates of CHD (estimated for 123 participants with diabetes at baseline and 701 “non-diabetes” participants); rate ratios for diabetes risk (95% CI), with “non-diabetes” participants as the reference group.Results: Participants with diabetes at baseline had a higher rate of CHD (37.5 per 1000 person-years) than those without diabetes (7.3 per 1000 person-years). Adjustment for multiple CHD risk factors, such as age, smoking, alcohol consumption, systolic blood pressure, body mass index, high-density lipoprotein cholesterol and total cholesterol levels, resulted in a CHD rate ratio for women of 3.7 (95% CI, 1.6–8.9) (comparing women with diabetes with those without) and a CHD rate ratio for men of 1.4 (95% CI, 0.4–4.1) (comparing men with diabetes with those without).Conclusions: Aboriginal women with diabetes experienced a significantly higher risk of CHD than women without diabetes. Although the difference was not statistically significant, women with diabetes had a higher CHD risk than men with diabetes.

Zhiqiang Wang PhD · Wendy E Hoy MB BS, BScMed, FRACP

Atherosclerosis and heart disease. Andrew M Tonkin (editor). London: Martin Dunitz, 2003 (xi + 235 pp). ISBN 1 84184 123 4. The Internet is great for reviewing literature rapidly, but the more I use it, the more I realise that the classic “Review article” has a role. PubMed can be very efficient for accessing publications, but drawing accurate conclusions can be hard work and reliance on abstracts can stifle critical analysis. Independent critical comment is difficult to find electronically. Journals realise they have to hold back some full-text editorial material for their loyal subscribers, and websites may be “free” because they are heavily sponsored. Systematic Cochrane-type reviews are readily accessible on the Internet, and are great if one needs to quantify evidence, but they can be a dull read. Tonkin’s book very effectively uses the classic “Review article” format in an ambitious attempt to review current knowledge on atherosclerosis and heart disease. The book consists of 15 chapters, covering the pathophysiology of atherosclerosis, each of the major coronary risk factors, the scientific basis of management of the main clinical coronary syndromes and the complications of coronary heart disease, including cardiac failure and arrhythmia. Tonkin is Director of Health and Scientific Affairs at the National Heart Foundation of Australia and he has selected some of the world’s most respected and influential practitioners in cardiovascular research to present authoritative and balanced overviews. Each is a very useful summary of current knowledge. There is some inconsistency in the format, with some chapters omitting detailed referencing and recommending “further reading”, while others are completely referenced, but this does not detract from the information presented. Clinicians and clinical researchers who want rapid access to balanced and reliable information on the commonest cause of premature death in this country will appreciate this book. For a compact and highly readable review of all the current work in atherosclerotic heart disease between two covers, it achieves its aim. Peter L ThompsonCardiologist and Clinical Professor of Medicine and Population Health University of Western Australia Perth, WA

Peter L Thompson

John Coutsouvelis,* Carmela E Corallo† * Oncology Pharmacist, † Deputy Director of Pharmacy, Box Hill Hospital, Nelson Road, Box Hill, VIC 3128. John.coutsouvelisATboxhill.org.au To the Editor: Thalidomide has recently been approved for use in treating recurrence of erythema nodosum leprosum and multiple myeloma after failure of standard therapies. Common side effects of thalidomide treatment include drowsiness, sedation, rash and paraesthesiae.1 Dizziness, hypotension and bradycardia occur less commonly.1-3 Of 91 patients treated with thalidomide (80 with multiple myeloma), we have had one case of symptomatic bradycardia. We describe this patient, who was able to continue treatment on a reduced dose of thalidomide. A 71-year-old woman, with a history of breast cancer (treated with radiotherapy and tamoxifen), arthritis, crush fractures, and hip and knee replacement, was diagnosed with multiple myeloma. She was prescribed intravenous pamidronate 90 mg every month and oral therapy with melphalan, but she experienced haematological toxicity and the melphalan was stopped. After progression of the disease, 100 mg of thalidomide was commenced at night, with the aim of increasing the dose by 100 mg every fortnight until a response was achieved. Three weeks later, the patient presented to hospital for pamidronate infusion complaining of a 2-week history of shortness of breath, especially on exertion. There was no oedema present, and her blood pressure was 135/70 mmHg. Electrocardiography showed sinus bradycardia, with a heart rate of 46 beats/min. The dose of thalidomide had been titrated to 200 mg at night. Thalidomide was stopped, and the patient was referred to a cardiologist, who performed an echocardiogram, 24-hour Holter monitoring and a stress test. The results from these tests showed no underlying cardiac disease or abnormalities. Six weeks later, on review, the bradycardia had resolved (heart rate, 60 beats/min). Thalidomide was recommenced at 100 mg daily. However, after a further 6 weeks, her heart rate had decreased again to 45 beats/min, and the dose of thalidomide was reduced to 100 mg on alternate days. Thalidomide therapy has been continued in this patient at 100 mg on alternate days. Her heart rate has stabilised between 50 and 55 beats/min, and she has remained asymptomatic. The multiple myeloma is responding to treatment, as indicated by symptom control and serial measurements of IgG kappa. She continues to take hydroxychloroquine, rofecoxib and sertraline. Bradycardia is a rare side effect of thalidomide therapy, with an incidence of 0.12%.1,2 The mechanism is unknown, but could be related to thalidomide’s central sedative effect.1 There are isolated published case reports of thalidomide-induced bradycardia; in all cases the drug was stopped.2-5 Thalidomide is being used for various conditions for which no alternative therapy exists. As the drug is now commercially available in Australia, its use is likely to increase. In all patients taking thalidomide, we recommend measuring heart rate; and in those with underlying heart disease, or who are taking medications that can precipitate bradycardia, we recommend electrocardiographic monitoring. Our findings in this patient suggest that thalidomide-induced bradycardia can be successfully managed with dose reduction and regular monitoring.

John Coutsouvelis · Carmela E Corallo

RCT evidence for rehabilitation is strengthened by an observational cohort study The study by Sundararajan et al1 (page 268) is a novel data linkage study and is best described as a cohort study. The study showed 35% lower mortality in patients with cardiovascular disease who had undergone cardiac rehabilitation when compared with patients who had not undergone cardiac rehabilitation. However, even the best cohort studies can give only limited inference on treatment effects. For example, observational studies suggested that women who used hormone replacement therapy (HRT) had a lower incidence of cardiovascular events than did non-users.2 However, not only did prospective randomised controlled trials (RCTs) fail to confirm the protective effect of HRT,3 they suggested that such treatment might actually cause cardiovascular disease.4 The apparent impressive protection of HRT suggested by observational databases may have been accounted for by socioeconomic differences between the users and non-users of HRT. Thus, RCTs have assumed the strongest evidence in suggesting a relationship between treatment and outcome. So why does the database linkage study by Sundararajan et al1 appeal at all? Perhaps it is because the evidence base for cardiac rehabilitation programs fails to convince all medical practitioners, despite “level 1” evidence existing from other studies.5 Even the best RCTs have intrinsic limitations. The first is that most trials exclude older, sicker patients with multiple comorbidities and those who might not cooperate with the trial protocol. This often results in a clinical trial of low-risk patients, which may miss a beneficial effect of treatment. The second limitation of RCTs, more common in single-centre studies, is publication bias. It is hard work to prepare a study for publication — even harder for a negative study than for a positive one. As a result, investigators are less likely to submit negative studies and journal editors are less likely to accept them for publication. Publication bias is likely to exist in most, if not all, areas of published research. So, what are the limitations of the evidence specifically regarding cardiac rehabilitation? The Cochrane Library review of exercise-based rehabilitation for coronary heart disease reviewed 51 RCTs of 8440 patients.5 Total cardiac mortality was reduced by 31% (random effects model odds ratio [OR], 0.69; 95% CI, 0.51–0.94) and 26% (random effects model OR, 0.74; 95% CI, 0.57–0.96) in the exercise-only and comprehensive cardiac rehabilitation groups, respectively. Neither intervention had any effect on the occurrence of non-fatal myocardial infarction. In other words, exercise that did not affect cardiac risk factors was as effective in reducing cardiac mortality as a comprehensive program that included exercise and successfully reduced cardiac risk factors. The reasons for this are unclear given the level 1 evidence supporting the proven effects of lowering blood pressure6 or serum cholesterol7 in reducing cardiac mortality. Furthermore, one has to be currently active to experience the benefit of physical activity or fitness — loss of activity and fitness means loss of the protection of exercise. So, medical practitioners can have reasonable doubts about the protective effects of a 6- or 8-week cardiac rehabilitation program on cardiac mortality years after the event, despite the Cochrane evidence. And this is why the data linkage article by Sundararajan et al appeals.1 The clinical trial data in the Cochrane review were derived from selected patients who had undergone exercise training for periods varying from a few weeks to several years. Sundararajan et al show that Australian patients with coronary heart disease who had undergone cardiac rehabilitation for 6–8 weeks had a better survival rate than did patients not undergoing cardiac rehabilitation. Although the study may be fraught with problems similar to those described for the HRT studies, it is pleasing to note how similar is the magnitude of protection from death associated with cardiac rehabilitation in this Australian series compared with that described in the Cochrane review. This observational study lends strong support to the trial information. Patients surviving an acute coronary syndrome should be referred for cardiac rehabilitation, as the experience may save their life. There is another nugget in the article by Sundararajan et al.1 Patients with acute coronary syndromes not undergoing coronary artery bypass surgery are very much less likely to undergo cardiac rehabilitation than patients who have received surgery. Percutaneous cardiac intervention is now performed twice as often as cardiac surgery. Such patients are often younger and fitter and return to work and their usual life within days of their procedures. Alternative models of rehabilitation are required for these patients who have not been physically deconditioned. These were recently discussed in this journal by Scott et al.8 One such model is the COACH Program, which has been validated by two RCTs.9,10 The COACH Program is a training program for patients with coronary heart disease, in which a healthcare professional coach trains patients to aggressively pursue the target levels for their particular coronary risk factors while working in partnership with their own doctors. The COACH Program has been shown to have a favourable effect on many coronary risk factors, including total and low-density lipoprotein cholesterol, arterial blood pressure, dietary saturated fat intake, body weight, and the performance of regular walking.8,9 If patients do not attend cardiac rehabilitation, then alternative strategies for achieving secondary prevention are required. The COACH Program is one such effective method. In summary, the evidence supporting cardiac rehabilitation is less than convincing, particularly when the rehabilitation is confined to the period after an acute cardiac illness. The data linkage study by Sundararajan et al adds support to the Australian practice of convalescent-phase cardiac rehabilitation.

V Michael Jelinek MD, FRACP, FACC

Objective: To describe the patterns of use of cardiac rehabilitation in Victoria and to assess whether the survival benefits predicted in clinical trials have been realised in the community. Design: Cohort study based on data linkage. Participants: All patients admitted for acute myocardial infarction (AMI), coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) in Victoria in 1998 (n = 12 821). Interventions: Attendance at one of 66 participating outpatient cardiac rehabilitation centres in Victoria. Main outcome measures: Rates of attendance at rehabilitation based on key factors such as diagnosis, age, sex, and comorbidity. Five-year survival for attendees compared with non-attendees. Results: Rates of participation in rehabilitation were 15% for AMI, 37% for CABG, and 14% for PTCA. Rehabilitation attendance rates dropped sharply after 70 years of age. Attendees had a 35% improvement in 5-year survival (hazard ratio for death associated with rehabilitation attendance, 0.65 [95% CI, 0.56–0.75]). Conclusions: Attendance rates at cardiac rehabilitation are suboptimal, even though attendance confers a clinically significant difference in 5-year survival. The elderly, women, and those with comorbid conditions may benefit measurably from increased rates of attendance.

Vijaya Sundararajan MD, MPH, FACP · Stephen Begg MPH · Ric Marshall PhD · Stephen J Bunker PhD · Helen McBurney PhD

QuestionWill implantation of defibrillators improve survival in patients with prior myocardial infarction and severely impaired left ventricular function? Trial detailsDesign: A prospective, randomised, non-blinded, multicentre, controlled trial of medical therapy versus implanted cardiac defibrillators (ICDs) in patients with severely impaired ventricular function resulting from prior myocardial infarction. Background: Patients with severely impaired left ventricular function are at high risk of sudden death from ventricular arrhythmias. The presence of spontaneous arrhythmias or arrhythmias induced at cardiac electrophysiological (EP) study identifies a high-risk group, but even in the absence of spontaneous or induced arrhythmias the risk of sudden death is considerable. The ICD is known to be effective in treating malignant ventricular arrhythmias. The MADIT-II trial was designed to evaluate the effect of an ICD on survival in patients with severe left ventricular dysfunction caused by previous infarction. Methods: 1232 patients from 76 sites were enrolled over 4 years. All had prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less, and were randomly assigned in a 3:2 ratio to receive a defibrillator (742 patients) or conventional medical therapy (490 patients). Spontaneous ventricular arrhythmias or EP testing were not required for entry into the trial. The primary endpoint was death from any cause. Results: The two treatment groups were similar at baseline with respect to clinical characteristics and medication use at the last follow-up. During a mean follow-up of 20 months, the mortality rate was 19.8% in the conventional therapy group and 14.2% in the ICD group. The hazard ratio for the risk of death from any cause in the defibrillator group compared with the conventional therapy group was 0.69 (95% CI, 0.51–0.93; P = 0.016). Subgroup analysis showed that defibrillator therapy improved survival regardless of age, sex, ejection fraction, New York Heart Association class or QRS interval. Conclusion: In patients with a prior myocardial infarction and advanced left ventricular impairment, prophylactic implantation of a defibrillator improves survival. CommentaryRationale for the trialFor several years, it has been routine clinical practice to implant ICDs in survivors of cardiac arrest or malignant ventricular arrhythmia. The prophylactic use of ICDs in high-risk patients who have not yet had a ventricular arrhythmia is more controversial. Patients with impaired left ventricular function are at high risk of malignant ventricular arrhythmias, but the implantation of a defibrillator is relatively expensive. There are large numbers of patients with impaired ventricular function, and to implant ICDs in all would place a considerable burden on the health budget. A possible solution is to identify those at highest risk using cardiac EP testing. The MADIT1 and MUSTT2 trials reported that ICDs improved survival in patients with coronary artery disease, reduced left ventricular function, non-sustained ventricular tachycardia, and inducible ventricular tachycardia at EP testing. Recent research, however, suggests that the EP study may be a relatively insensitive method of identifying those at highest risk.3 Moreover, it appears that the lower the left ventricular ejection fraction, the less sensitive the EP study becomes. The MADIT-II study was designed to investigate the potential survival benefit of ICDs in those without spontaneous arrhythmias and without performing EP testing.4 Trial methodsThe trial methods were relatively sound. The sample size (1232 patients from 76 sites in the United States and Europe) was adequate. Random allocation of patients resulted in well-matched treatment groups with similar baseline characteristics and similar medical therapy at last follow-up. Treating physicians were encouraged to prescribe effective drug therapy for heart failure and to minimise the use of conventional antiarrhythmics. Similar proportions in both groups received angiotensin-converting enzyme inhibitors, β-blockers and statins. Attendance rates at follow-up were 94% in the conventional therapy group and 97% in the defibrillator group. The trial was open label because blinding was not practical, but the primary end-point was unequivocal — death from any cause. However, a criticism is that mean follow-up was only 20 months, and this may impair assessment of cost-effectiveness. Another criticism is that when the trial commenced in 1997, a selection criterion was that patients have frequent spontaneous or repetitive ventricular premature contractions. This requirement was removed 6 months later, but only 23 of the 1232 patients were enrolled in those first 6 months. New informationThe trial showed that ICDs improve survival in patients with severely impaired left ventricular function caused by previous myocardial infarction, even in the absence of spontaneous arrhythmias or inducible arrhythmias at EP testing. A disturbing finding was that new or worsening heart failure requiring hospitalisation was more frequent in the ICD group. The cause of this is uncertain. One possible explanation is that the patients in the ICD group lived longer and therefore had more time to develop cardiac failure. Another is that the cardiac failure was caused by asynchronous ventricular contraction caused by ventricular pacing. The results of the recent DAVID5 trial tend to support the latter hypothesis. If this is indeed the case, the cardiac failure can probably be reduced by judicious programming of the pacing function of the ICD. Implications for clinical practiceThe routine use of ICDs in patients with an ejection fraction of 0.30 would have profound implications for healthcare spending. Routine use of ICDs for this indication would potentially increase the number of implants by a factor of between 10 and 30 per annum. Currently, about 950–1000 ICDs are implanted annually in Australia and New Zealand, at a total cost for hardware alone of about A$30 million (my estimates based on information obtained from device manufacturers). A 15-fold increase in the implantation rate would result in an increase in the annual cost for the hardware alone of about A$420 million. This is about twice the annual budget of a large Australian teaching hospital. This figure does not take into account the increase in hospital and professional fees. Moreover, it is uncertain that there are enough trained cardiac electrophysiologists to implant defibrillators in and follow up such a large number of patients. By comparison, Australian national spending on the lipid-lowering “statin” drugs in the 2001–2002 financial year was about A$670 million.6 Australian cardiologists have not yet embraced the findings of MADIT-II. This is probably because of the cost implications, preferring to wait until the findings are confirmed in other large trials. However, preliminary reports of the COMPANION7 trial appear to confirm the MADIT-II findings (the study populations of these two trials are not strictly comparable). The findings of another large trial of prophylactic ICD use, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), will soon be reported, and might shed additional light on this question. The true cost of implementing the MADIT-II findings awaits a detailed cost–benefit analysis. The cost of ICD hardware has been falling for several years, but it is difficult to predict the magnitude of future cost reductions. It may be possible to identify a low-risk cohort which will not benefit from ICD implantation, but the preliminary results are not encouraging. Recently, in the United States, the Centers for Medicare and Medicaid Services approved the use of ICDs in Medicare patients meeting the MADIT-II inclusion criteria and having a QRS duration of more than 120 ms. This decision was based, in part, on a subsequent analysis of the MADIT-II data, which showed that the benefit was greatest in this group of patients.8 The MADIT-II trial is likely to provoke vigorous debate over the best use of healthcare spending for some time to come.

Bruce P Wilson FRACP · Mark A McGuire PhD, FRACP

Objective: To assess if there are any differences in statin prescribing across Australia by socioeconomic status or sex and to relate prescribing rates to coronary heart disease (CHD) mortality rates.Design: Cross-sectional study using data on statin prescribing by age, sex and patient postcode for the period May to December 2002.Setting and participants: The Australian population, stratified by sex and quintile of Index of Relative Socio-Economic Disadvantage (IRSD).Main outcome measures: Age-standardised rates of statin scripts per 1000 population per month for each sex and IRSD quintile.Results: 9.1 million prescriptions for statins were supplied between May and December 2002, for a total cost of $570 million. The age-standardised rates for statin prescribing in women varied from 56.9 (95% CI, 56.6–57.2) scripts per 1000 population per month in the most disadvantaged socioeconomic quintile through 53.4 (95% CI, 53.0–53.7), 50.3 (95% CI, 50.0–50.6), 48.4 (95% CI, 48.1–48.7) to 46.3 (95% CI, 46.0–46.6) in the least disadvantaged quintile. For men the figures were 52.6 (95% CI, 52.3–52.9), 50.9 (95% CI, 50.6–51.2), 48.8 (95% CI, 48.6–49.1), 47.7 (95% CI, 47.4–47.9), and 51.9 (95% CI, 51.6–52.2). There was a significant linear association between statin prescribing and CHD mortality by quintile of socioeconomic disadvantage in women (weighted least squares slope, 0.380; 95% CI, 0.366 to 0.395; P < 0.0001), but not in men (slope, − 0.002; 95% CI, − 0.010 to 0.006; P = 0.65).Conclusions: Our results suggest that in men there is either overprescribing of statins in the highest socioeconomic quintile or underprescribing in the lowest. Furthermore, contrary to expectation, women — relative to men — are prescribed statins at higher rates at lower levels of risk (using CHD deaths as a proxy measure of risk).

Nigel P Stocks MD · Heather McElroy DipStats · Philip Ryan MB BS · James Allan MB BS

Neil H Cradick General Practitioner, PO Box 1127, Buderim, QLD 4556. cradwhitAToptusnet.com.au To the Editor: On opening the MJA Focus document “Prevention of cardiovascular disease: an evidence-based clinical aid”,1 I expected to find useful and contemporary guidelines for general practice. However, I was surprised to read two of the recommendations — for the use of antihypertensive and antiplatelet drugs in “low risk” patients (those without risk-associated clinical conditions or end-organ damage). The document recommends drug treatment only if systolic blood pressure is > 180 mmHg or diastolic blood pressure is > 100 mmHg in people under 60 years, or systolic blood pressure is > 160 mmHg in people over 60 years. While Fulcher et al1 volunteered that this was at odds with clinical practice, they supported the recommendations by stating that they were in accordance with published guidelines. The data for these conservative hypertension parameters were published nearly 10 years ago,2 or derived from textbooks,3 and are at odds with the 1999 WHO/ISH guidelines,4 and even more at odds with the excellent Joint National Committee (JNC 7) report.5 The latter publication recommends, after lifestyle recommendations, drug treatment for a blood pressure of 140–159/90–99 mmHg for those without end-organ damage. Furthermore, the focus document recommends primary prevention with aspirin in those with a calculated annual cardiovascular event risk > 3%. Hayden et al6 suggest antiplatelet treatment should be offered to those with a 5-year cardiovascular event risk > 3%, which equates to a > 0.6% annual risk. The benefit to harm ratio needs to be explained to the individual, and therapy should only be initiated once blood pressure is controlled. As an interested general practitioner and user of evidence-based guidelines, I usually check the funding of publications, and, with the heavy emphasis on the use of ACE inhibitors (in particular ramipril) and statins (which are produced by Aventis Pharma), it is difficult to rely on the evidence as presented. I would hope that independent bodies such as the National Prescribing Service or Australian Prescriber could take the pharmaceutical lead and produce desktop references with a more unbiased opinion on the latest collection of evidence that is shaking us up in primary care medicine. I would again refer readers to the excellent hypertension guidelines mentioned above4,5 (in particular the JNC 7 reference card available on the Internet at www.nhlbi.nih.gov/guidelines/hypertension/jnc7card.htm), and caution them to remain wary of easy-reference desktop items funded by pharmaceutical companies.

Neil H Cradick

Gregory R Fulcher,* John V Amerena,† Greg W Conner‡ * Director, Department of Diabetes, Endocrinology and Metabolic Medicine, Level 3, Main Block, Royal North Shore Hospital, St Leonards, NSW 2065; † Cardiologist, Department of Clinical and BioMedical Sciences, University of Melbourne, Melbourne, VIC; ‡ Vascular Physician, Cardiovascular Diagnostic Services, Sydney, NSW. gfulcherATmed.usyd.edu.au In reply: We thank Cradick for his critical review of our publication.1 His interesting points illustrate some of the reasons we were keen to publish this work. Firstly, the average practitioner is confused about which guidelines (both national and international) to follow. Cradick refers to the JNC 7 report and WHO/ISH guidelines (the committee is familiar with these), but which to follow? The committee decided a priori that Australian national guidelines, if they existed, would be referenced in preference to overseas ones. We mentioned that current Australian hypertension guidelines should be revised, and that clinical practice was probably at odds with these recommendations. Secondly, guidelines quickly become dated. Cradick cites the recommendation of Hayden et al that aspirin should be introduced if the annual risk of a cardiovascular event is > 0.6%.2 The latest Australian guidelines3 recommending a > 1% annual risk as the treatment threshold were published just after we received Cradick’s letter. The Hayden article is thus (for some patients) at odds with current local recommendations. Consistent with our approach, we will include the Australian recommendations in the first update of our document (July 2004). Cradick’s comments imply bias in the presentation of the data; yet he fails to substantiate this. Neither the clinical trials quoted (nearly all of which are funded by the pharmaceutical industry) nor the conclusions or inferences drawn have been challenged. He refers to the “heavy” emphasis on the use of ACE inhibitors and statins, implying that this is inappropriate. We would argue that, given the strength of the evidence, this emphasis is appropriate, and reflects current specialist practice in tertiary centres. Careful reading of the National Prescribing Service publications will show that “heavy” reference is made to the 4S,4 LIPID,5 CARE,6 and WOSCOPS7 studies (for example, NPS News 20 February 20028), as well as to the prescribing information for Lipitor (Pfizer), Pravachol (Bristol-Myers Squibb) and Zocor (Merck Sharp & Dohme). We must caution against “throwing the baby out with the bathwater”. The HPS, CARE, LIPID, WOSCOPS, HOPE, PROGRESS, 4S, CURE, and CREDO studies represent substantial and widely acclaimed clinical trials that have had a positive impact on clinical care. They have all been funded by the pharmaceutical industry. Finally, about 130 GPs in clinical practice had some input in compiling and formatting this document. The document was tested before publication in over 30 000 patients, and was peer reviewed by several clinicians. It is a pity that Cradick was not a participant in any of these processes.

Gregory R Fulcher · John V Amerena · Greg W Conner

Objectives: To determine the causes of sudden cardiac death in people aged 35 years or younger.Design and setting: A review of all autopsies performed between 1 January 1994 and 31 December 2002 at a major Sydney forensic medicine department serving an area with over 2 million people.Main outcome measures: Incidence of various types of cardiac disease causing sudden death in those aged ≤ 35 years; proportion of deaths in which no cause was found at autopsy.Results: There were 10 199 autopsies performed during the study period. Of these, 2986 (29.2%) deaths occurred in people aged ≤ 35 years; 193 were classified as sudden cardiac deaths. The cause of sudden death in this group was not established in 60 (31%), and was presumed to be due to primary arrhythmogenic disorders. Coronary artery disease occurred in 46 (24%), hypertrophic cardiomyopathy/unexplained left ventricular hypertrophy in 29 (15%), and myocarditis in 23 (12%).Conclusions: Unexplained deaths, presumed to result from sudden primary arrhythmogenic causes, occur in young Australians with structurally normal hearts. That underlying disease-causing genetic defects may be involved has clinical implications for family members.

Alessandra Doolan BMedSc · Christopher Semsarian MB BS, PhD, FRACP · Neil Langlois MB BChir, MD, FRCPA

Matthew T Naughton,* Darren R Mansfield,* David M Kaye,† Peter Bergin,† Meroula Richardson† * Respiratory Physician, † Cardiologist, Alfred Hospital, PO Box 315, Prahran, VIC 3181. m.naughtonATalfred.org.au To the Editor: We were surprised that Campbell’s recent article on heart failure1 made no mention of sleep apnoea. This is despite the fact that about 50% of heart failure patients have sleep apnoea (either central or obstructive) and that quite a large body of literature now supports a causative relationship between obstructive sleep apnoea and congestive heart failure, supported by recent authoritative reviews. 2-4 Canine studies have shown that, in the absence of any other variable, obstructive sleep apnoea results in left ventricular systolic and diastolic dysfunction. Importantly, the impact of continuous positive airway pressure (CPAP) in acute cardiogenic pulmonary oedema and subacute pulmonary oedema (central sleep apnoea) and heart failure in the setting of obstructive sleep apnoea are not mentioned. Identification and treatment of sleep apnoea in people with heart failure is supported by a trial we have recently conducted in which significant improvements in quality of life and objective markers of cardiac function were seen in patients treated with nasal CPAP.5

Matthew T Naughton · Darren R Mansfield · David M Kaye · Peter Bergin · Meroula Richardson

Duncan J Campbell Senior Research Fellow, St Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, VIC 3065. J. CampbellATmedicine.unimelb.edu.au In reply: I am grateful to Naughton and colleagues for their contribution to the debate about how we might prevent the epidemic of heart failure. I agree that both obstructive and central sleep apnoea are frequently associated with heart failure and that treatment of sleep apnoea can improve cardiac function. However, as indicated by its title, my article focused on how we might prevent heart failure. Central sleep apnoea in heart failure is usually the consequence of the heart failure.1 Heart failure may contribute to obstructive sleep apnoea as well,2 and obstructive sleep apnoea may, in turn, be an important contributor to heart failure pathogenesis. Epidemiological evidence links obesity with hypertension and obstructive sleep apnoea.3 Significant sleep apnoea is present in about 40% of obese people, and about 70% of people with obstructive sleep apnoea are obese.3 Obesity and obstructive sleep apnoea may each contribute to one another, and both may contribute to hypertension. The need to prevent obstructive sleep apnoea is an argument for more effective prevention of obesity. In addition to reducing its metabolic consequences, preventing obesity is likely to reduce the incidence of hypertension and obstructive sleep apnoea, and to thereby decrease the incidence of heart failure. For people with obstructive sleep apnoea not caused by obesity, alternative strategies will be required to prevent and treat the sleep apnoea and thus prevent its consequences.

Duncan J Campbell

Balakrishnan R Nair,* Brendan Flynn† * Director, † Medical Registrar, Division of Geriatric Medicine, John Hunter Hospital, New Lambton, NSW 2291. knairATmail.newcastle.edu.au To the Editor: We refer to the recent article by Parslow and Jorm1 and the editorial by Headey2 on the link between pet ownership and health outcomes. There is no evidence that pet ownership per se confers cardiovascular benefits. Indeed, the findings of the study were that pet owners were more likely to smoke, had a higher diastolic blood pressure and a higher body mass index than the non-pet owners. The editorial points out that, based on sociological studies, it is likely that pet ownership does have a positive effect on health, but the medical data demonstrating how this is achieved are lacking.2 Might there be other negative effects of pet ownership on health outcomes? A patient under our care recently demonstrated the potential risks involved in pet companionship for elderly people. An 81-year-old woman who was living independently was admitted after a fall caused by tripping over her delightful Himalayan Persian cat. Her presenting symptom was severe back pain exacerbated by weight bearing. However, no bony abnormality was identified. She had difficulty mobilising initially, and the outcome of her fall was significant morbidity with some loss of her previous mobility, even on discharge. She stayed in hospital for 12 days. A follow-up phone call revealed that the patient was still experiencing difficulty mobilising some 2 weeks after discharge. This case raises the possibility that the risks may outweigh the benefits of pet ownership in elderly people who are already at risk of falls. A MEDLINE search, using the terms elderly, trauma, cat, pet and fall (and combinations of these), did not reveal any relevant literature. A recent case report highlighted other cardiovascular issues relating to cat ownership.3 It described a patient who had recurrent episodes of syncope whenever her cat slept on the right side of her neck. The underlying mechanism was carotid sinus hypersensitivity. She required a single-lead ventricular pacemaker and for the cat to lie on her left side. Anecdotal evidence from colleagues highlighted the danger of “dogs taking elderly patients for walks”, resulting in rotator cuff injuries. Additionally, older patients with peripheral vascular disease and fragile skin have presented with non-healing ulcers from dog scratches. Pet ownership for the purpose of modifying cardiovascular risk factors would seem to be unwise in this population. However, the benefits of companionship and the pleasure derived from pets may outweigh the risk of falls for many elderly patients. Should we be doing more “cat scans” or “pet scans” in older patients?

Balakrishnan R Nair · Brendan Flynn