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

Objective: To estimate Pharmaceutical Benefits Scheme (PBS) subsidies for drugs to treat smoking-related cardiovascular disease (CVD) in 2001–02, and over the period of the government’s Intergenerational Report (IGR), assuming current smoking prevalence rates and a 5% absolute reduction.Design and setting: An Australian epidemiological study, using prescribing data, aetiological fraction methodology, and IGR trends.Main outcome measures: Estimated smoking-related PBS subsidy costs in 2001–02 and predicted cumulative subsidies until 2041–42, under current and reduced smoking prevalence assumptions.Results: The PBS costs of smoking-related CVD in 2001–02 were $126 million, 9.77% of the cost of drugs for CVD and 2.96% of total PBS subsidies. The cumulative difference in these costs over the 40-year period with a 5% drop in smoking prevalence was predicted to be $4.5 billion, a 17% reduction. The saving would be $1.14 billion discounting future costs at 5% per year.Conclusions: Further investment in tobacco control interventions could curb the increasing cost of the PBS and contribute to government efforts to ensure the viability of Australia’s healthcare-financing programs. The net present value of a campaign to reduce smoking prevalence was estimated at $1 billion, with an internal rate of return of 33%.

Susan F Hurley MS, PhD · Michelle M Scollo BSc, GradDipCommHlth, CertHlthEcs · Sandra J Younie PostgradDipHealthEc · Dallas R English PhD · Maurice G Swanson BSc, MPH

Objective: To determine risk factors for ischaemic stroke recurrence among patients admitted to hospital for a first-ever occurrence of ischaemic stroke.Design, setting and patients: Retrospective study involving linked hospitalisation and death records. The cohort comprised 7816 people who were hospitalised for first-ever ischaemic stroke between July 1995 and December 1999 in Western Australia. Cox’s proportional hazards model was used to identify risk factors for stroke recurrence.Main outcome measures: Time to first recurrence; cumulative recurrence risk; risk factors for recurrence.Results: The median time to first stroke recurrence was 255 days. The cumulative probability of first recurrence was 5.1% (95% CI, 4.6%–5.7%) at 6 months, 8.4% (95% CI, 7.6%–9.1%) at 1 year and 19.8% (95% CI, 18.1%–21.4%) at 4 years. The risk of first recurrence was increased by advancing age (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04), Aboriginality (HR, 1.50; 95% CI, 1.02–2.22), diabetes (HR, 1.27; 95% CI, 1.07–1.51), a history of cardiac conditions (HR, 1.18; 95% CI, 1.01–1.38), post-stroke urinary incontinence (HR, 1.27; 95% CI, 1.03–1.57) and transfer to another hospital on index admission (HR, 1.26; 95% CI, 1.08–1.46). Admission at first stroke occurrence to a hospital maintaining a stroke unit reduced the risk of recurrence (HR, 0.84; 95% CI, 0.72–0.99).Conclusion: The risk factors identified in our study have implications for planning secondary prevention strategies. In particular, Aboriginality and transfer to another hospital upon admission for first-ever ischaemic stroke were important risk factors. Research into the level of compliance and access to stroke treatment by Aboriginal patients to prevent further strokes is required.

Andy H Lee PhD · Peter J Somerford BSc · Kelvin K W Yau PhD, AStat

Objective: To assess the effect of home-based health assessments for older Australians on health-related quality of life, hospital and nursing home admissions, and death.Design: Randomised controlled trial of the effect of health assessments over 3 years.Participants and setting: 1569 community-living veterans and war widows receiving full benefits from the Department of Veterans’ Affairs and aged 70 years or over were randomly selected in 1997 from 10 regions of New South Wales and Queensland and randomly allocated to receive either usual care (n = 627) or health assessments (n = 942).Intervention: Annual or 6-monthly home-based health assessments by health professionals, with telephone follow-up, and written report to a nominated general practitioner.Main outcome measures: Differences in health-related quality of life, admission to hospital and nursing home, and death over 3 years of follow-up.Results: 3-year follow-up interviews were conducted for 1031 participants. Intervention-group participants who remained in the study reported higher quality of life than control-group participants (difference in Physical Component Summary score, 0.90; 95% CI, 0.05–1.76; difference in Mental Component Summary score, 1.36; 95% CI, 0.40–2.32). There was no significant difference in the probability of hospital admission or death between intervention and control groups over the study period. Significantly more participants in the intervention group were admitted to nursing homes compared with the control group (30 v 7; P < 0.01).Conclusions: Health assessments for older people may have small positive effects on quality of life for those who remain resident in the community, but do not prevent deaths. Assessments may increase the probability of nursing-home placement.

Julie E Byles PhD · Meredith Tavener BAppSci(Hons), MMedSci · Nick H Higginbotham PhD · Lyn Francis BN, MHM · John E Marley MD · Rachel L O’Connell BMath, MMedStat · Balakrishnan R Nair FRCP, FRACP · Brendan G Goodger PhD · Claire L Jackson MB BS, MPH · Mary E McKernon DipAppSci(Commun Nurs), GradDip(Nurs Admin) · Richard F Heller MD, FRACP · Jonathan Newbury MD

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

The National Health Service (NHS) has undergone fundamental reform since 1948, but the fabric of UK general practice remains more or less intact. Fundholding was probably the most significant change in financial arrangements (Box). Essentially, this was an experiment for the NHS to contain costs, stimulate competition and bring resource allocation decisions closer to the patient — fundholding general practitioners assumed significant roles in local healthcare economies. Nevertheless, there was much debate over whether it was equitable. Many saw it as a basis for partnerships with the private sector and fragmentation of the healthcare service.1 Others showed that it reduced non-emergency medical admissions.2 Fundholding grew from the Thatcher government’s strongly held belief that markets are the best way to achieve efficiency in healthcare. At the same time, fundholding established general practice as the cornerstone of the NHS.3 Further, it brought a questioning of the “status quo” in the NHS, and the prospect of higher standards of care. These expectations remain in the eyes of the public, government and the profession. Reforms aside, under “standard” contracts, UK general practitioners have been rewarded for increasing patient list size, and for providing specific services to achieve target payments. Unlike in Australia, there is no incentive to overservice, but an incentive to limit the availability of appointments, and pressure to keep appointment times to a minimum. Interestingly, salaried GPs in the personal medical services pilots (Box) have similar productivity without affecting other GP behaviours or quality of care.4 The new contractThe new GP contract, operative from April 2004, brings more funding, fundamental structural change, greater regulation and performance monitoring. There are concerns that many of the quality targets (eg, the incentive to diagnose, investigate and treat hypertension) have not been adequately costed.5 Further, this new environment has a strong emphasis on performance management and holding doctors to account. Some people see this as an erosion of public trust in the medical profession, which could undermine doctor–patient relationships; others see it as an essential mechanism of delivering proven, cost-effective care. For patients, NHS general practice is well integrated with the wider health service, and gives access to a multidisciplinary primary care team, including health visitors and practice nurses. On the downside, a non-competitive system means there are not the same incentives to attract patients as exist in Australia’s fee-for-service environment, and there is a culture of demand management, which often takes precedence over making services attractive and convenient to patients. In many ways, the NHS places GPs at the centre of the healthcare service and gives one a sense of being part of a team, with less of the fragmentation and isolation that often exists in Australian general practice. Whether the new GP contract will improve experiences and outcomes for patients, at a cost the NHS can afford, remains to be seen. On the downside, many GPs believe the wider healthcare service has not been able to accommodate the needs of patients in recent years; this may, despite the best efforts of individual primary care teams, lead to a demoralised workforce. Towards the end of New Labour’s second term, the NHS is being pulled in several directions — involving performance management, quality payments, new contracts, and greater engagement with the private sector, including American managed care organisations. The competition and “constructive dissonance” of these changes is very reminiscent of the Thatcher reforms. How general practice will fare in this turbulent environment is unpredictable, but no doubt being a GP or a patient in the NHS will be a very different experience in 2010. How it works Most UK general practitioners are independent contractors with the National Health Service. They own their own premises, hire their own staff, and supply general medical services. Remuneration is based mainly on capitation (ie, a payment dependent upon list size), supplemented by fees for certain specific services (eg, maternity care) and for achieving certain “target” levels of service (a complex system, although it only involves childhood vaccination and cervical cytology). Payments are also made for seniority and postgraduate education activities. Alternatives: the NHS (Primary Care) Act of 1997 allowed GPs to provide “personal medical services” (PMS) on a salaried basis through local service contracts that are designed to meet the particular needs of the locality. More than 35% of GPs are now salaried. Fundholding was a system of general practice purchasing services from secondary care. It operated between 1991 and 1999. Fundholding practices were given greater autonomy over aspects of practice expenditure such as drugs, diagnostic testing and staffing (within defined budgets), and could “shop around” for the best deal on procedures such as hip replacement. A further initiative, “total purchasing”, allowed practices to purchase a wider range of services from both primary and secondary care — for example, community nursing. Primary care trusts were established in 1997 (they began as primary care groups; in England, these became trusts in 2002, but have taken different forms in Scotland, Wales and Northern Ireland). Individual practices were replaced as purchasers by regional organisations, which could assess and plan for local needs. A new GP contract took effect in April 2004, with GP payments more closely linked to “quality targets” for both clinical and organisational activity. This has been coupled with increased funding and structural change — for example, GPs are no longer obliged to provide out-of-hours services, and the contract is with whole practices rather than individual GPs.

David P Weller FRACGP, MPH, PhD · Alan Maynard DSc, FAMS, MFPHM

It was towards the end of 1963 — my final year of medical school at the University of Melbourne — when I read about the new contraceptive method in the Medical Journal of Australia. On our last day, after the Professor of Obstetrics and Gynaecology bade us farewell, I ran after him and asked: “Professor Townsend, what do you think about the Pill?” “It’s good stuff,’’ he replied, with a smile and a wink. And so I began my career just as the sexual revolution was poised to change society forever. One of my first patients was a migrant from Eastern Europe, who was raising two children as a single mother in the days before the safety net of generous social security benefits. She performed her own abortion with a knitting needle when I could not find a doctor to do it for her. But, as the years went by, struggling women and blushing teenagers came to me instead for “Anovlar”. Gradually, the unwanted pregnancy became less common, and so, thankfully, did the do-it-yourself abortion. In 1963 there were few female GPs. Indeed, some patients never came into contact with a female doctor. Once a 3-year-old child of one of my patients, staring with a puzzled look as I examined his mother, asked in Hungarian: “Mummy, is this lady a gentleman?”. Our family practice was situated in Elwood, a suburb that was then a bit “rough around the edges”. The practice started in a flat, with the living room serving as the waiting area. This arrangement did not worry our fellow compatriots and the other colourful immigrants of various religious and ethnic backgrounds who streamed through the doors. And Australian women came from all over Melbourne to see a female doctor for their “women’s problems”. Gifts of paintings, flowers, handcrafts, boxes of chocolates, and silver plates engraved with messages of gratitude all adorned our home. Every year I still receive a Christmas present from an Italian family I stopped treating long ago. We worked 6 days a week and attended emergency calls each night. There was no time to stop and smell the roses; I noted the changing seasons by the reappearance of patients with chronic peptic ulcers in the spring and autumn. What a difference the first histamine H2-receptor antagonist made! Not to mention proton-pump inhibitors. I often think about the patients who suffered penetrated, perforated or bleeding ulcers before the advent of these drugs. I can recall more recent cases too, but most of these were iatrogenic, as a result of taking non-steroidal anti-inflammatory drugs (NSAIDs). When I started practice, phenylbutazone was the only anti-inflammatory drug available, and I’ll never forget the life-threatening Stevens–Johnson syndrome that it caused in one of my patients. It was a relief when indomethacin and the other NSAIDs, and later still the COX-2 inhibitors, came along as alternatives. The way we viewed and treated cardiovascular disease changed over the years. In the early days our waiting room was awash with ashtrays. We doctors sometimes even smoked with our patients! We also knew all about the links between cholesterol and heart disease, but didn’t take it too seriously, as there were no effective cholesterol-lowering drugs. I remember attending patients with suspected acute coronary occlusions in the surgery, in their homes, on the street, and on garage floors. They were common occurrences, and neither ambulances nor hospitals had coronary care facilities or units. Still, I clearly remember saving the lives of two patients by rushing them to hospital and arriving just minutes before they had a cardiac arrest. The treatment for hypertension was straightforward and simple compared with the choices we have now. We used mainly Aldomet and chlorothiazide; our aim was a blood pressure of 140/90 mmHg, although 150–170/90–95 mmHg didn’t alarm us. In the elderly, high systolic pressure was generally not treated if the diastolic pressure was normal. In those days, near enough was good enough. The new and effective cardiovascular drugs came slowly, and a few decades later we began to notice that our patients were living longer and not succumbing to early heart attacks and strokes. I often think with great sadness of the friends and patients who died at that time, but might have been saved with better medications or bypass surgery. I still remember the suffering of patients with severe chronic asthma that I couldn’t adequately treat. All we had was ephedrine and phenobarbitone, combined with aminophylline or theophylline. We used adrenaline in emergencies, and also had prednisolone, but did not know how to use it safely. No wonder we embraced the first salbutamol and steroid inhalation devices, and later the individual asthma management plans, so enthusiastically! In the late 1960s, I saw a one-year-old baby with a minor complaint. To my horror, the next patient was an 8-year-old with a high temperature, cough and Koplik spots. I feared for the baby, who would surely catch measles from the 8-year-old. I knew the incubation period for measles was 2 weeks, but remembered reading about a new vaccine that gave protection within a week. I urged my pharmacist to try to obtain the vaccine for me, as it was not yet readily available. Luckily, it arrived and was given to the baby the same night. He never developed measles! I probably overprescribed antibiotics for many years, especially penicillin, but I am proud that no child in my practice ended up with damaged eardrums, rheumatic fever, nephritis or chronic chest infection, and I can’t remember many tonsillectomies either. On the other hand, a lot of patients developed thrush. I remember using antiviral drugs for the first time — to treat herpes zoster and a severe case of genital herpes — and dreading the side effects that, in fact, never came. We used barbiturates freely for anxiety, nervousness and sleeplessness. The 30 mg amylobarbitone (Amytal) was even more popular than Valium is today. The 200 mg dose Sodium Amytal was a good hypnotic — and a common cause of successful suicide! One of my patients took all 25 capsules, never to wake again. By contrast, not so long ago, one of my young patients reported downing 25 Mogadon tablets at once. “What happened?” I asked. “I woke up 2 days later,” she replied. “How did you feel?” “Very hungry!” No wonder, given their obvious safety (although, of course, it’s no excuse), we overprescribed the benzodiazepines. It is still an ongoing problem. The introduction of ultrasound, computed tomography scanning and endoscopy, and the new, less invasive surgical procedures, had a revolutionary effect. I remember the first of my patients who braved a laparoscopic cholecystectomy when it was still a very new procedure. Both of us were pleased with the outcome. Substance misuse, especially drug addiction, was always a problem in the Elwood area, and sadly remains so. The relationship between user and doctor was mutually unsatisfactory. The addict failed me by lying, cheating and stealing. They came not for help, but for drugs. I, in turn, failed them, because I refused to supply the drugs they craved. Even little things like disposable syringes, office pregnancy tests and one-drop blood sugar testers represented a great leap forward. Later still came the mobile phone and the computer, and no more arriving home only to be immediately called out again, and no more misplaced reports. Medicare deserves a whole chapter. For my practice, it meant I could order pathology or radiology services for pensioners, who previously had to attend public hospitals for these services. Sometimes, very poor patients were given free treatment, and this dilemma was also solved by bulk-billing. As the years flew by we had to learn about new diseases and their social impact, such as chronic fatigue syndrome, and new infectious diseases — AIDS, hepatitis B and C and, most recently, SARS. And diseases that were once less prevalent, such as type 2 diabetes mellitus and breast and prostate cancers, now became more common. As people ate more and exercised less, obesity reached epidemic proportions. Sleeping with multiple partners increased the prevalence of genital herpes. When I first started, choosing specialists was easy. Today, it is a matter of matching the right specialist to the right condition, as specialists themselves are now increasingly specialised. You have to know which orthopaedic surgeon is experienced at hip replacements, and which gynaecologist treats stress incontinence. But along with the new advances came the demise of the “old-style” doctor, devoted to treating several generations of the same family — the doctor who does home calls and has patients whom he or she has seen for 40 years or more. Now, fewer and fewer doctors are willing to do house calls, while the public expects service from early morning to late at night and during weekends, something no single doctor can provide. Doctors, whose only duty was to look after their patients, now spend a lot of time and money protecting themselves from potential litigation. With these pressures, I too eventually joined a mega-clinic with efficient, up-to-date, accredited services. The patient care is excellent, but also less personal. And while we look to evidence-based medicine, the public spends more and more money on poorly regulated and sometimes harmful “natural” therapies. So, how would a wish-list of a doctor nearing the end of her working life read? What do I want that we still haven’t got? Try this: a simple, non-invasive test for detecting colon carcinoma; clearer guidelines about when and how to investigate patients with high erythrocyte sedimentation rates and high C-reactive protein levels; still safer NSAIDs; guidance on when to stop postponing death and begin palliative care; a clever device for testing blood sugar that would administer insulin automatically; more places for taking long walks safely in our suburbs and towns; a society in which families take more responsibility for their elderly relatives; baby-friendly workplaces; and less violence in films, videos, computer games and, of course, in life itself. Yes, general practice has “all changed, changed utterly”*. *Easter 1916 — William Butler Yeats

Eva Szego MB BS

Objective: To assess primary care processes and clinical characteristics of adults with diabetes in remote northern Australian Indigenous communities.Design: Clinical audit from diabetes registers in 21 remote primary healthcare centres in the Torres Strait Health Service District (n = 921), three in Cape York, Queensland (n = 252), and three in the Northern Territory (n = 194), between September 2002 and February 2003.Participants and setting: Aboriginal and Torres Strait Islander adults with diabetes who were receiving their routine diabetes care in these 27 centres.Main outcome measures: Provision of regular checks for weight, blood pressure, glycaemia (HbA1c), proteinuria, lipid levels, renal function, eyes and feet, influenza and pneumococcal vaccination. Weight, blood pressure and glycaemic control.Results: Most routine diabetes checks were delivered according to recommended schedules, except for eye and foot checks in the NT. There were uniformly high rates of appropriate treatment for hypertension and albuminuria, but low rates of insulin treatment and self-monitoring despite a high mean HbA1c level (8.9%). Vaccination rates were low in the NT. Torres Strait Islanders with diabetes were significantly heavier than Aboriginals, but had lower mean diastolic blood pressure (77.3 mmHg compared with 79.5 mmHg) and lower prevalence of albuminuria and smoking.Conclusion: A high proportion of Aboriginals and Torres Strait Islanders requiring treatment for high blood pressure and proteinuria are receiving it. However, there is dissonance between the relatively high rates of routine checks and apparent lack of therapeutic action on glycaemia. More intensive management of glycaemia, including improved nutrition, exercise and (probably) insulin, is required to reduce microvascular complications.

Robyn A McDermott FAFPHM, PhD · Fiona Tulip AssocDipMRA · Barbara Schmidt BSc, MBA

Peter J Fenner National Medical Officer, Surf Life Saving Australia, Sydney, NSW, and Associate Professor, School of Medicine, James Cook University, Townsville, QLD; PO Box 3080, North Mackay, QLD 4740. pjfennerATozemail.com.au In reply: We did not provide evidence of any effect on pulmonary oedema, myocardial injury or any effect in stopping pain, as that was not our intention. Also, even intravenous nitrates that have been used for many years in hospital are ineffective in reducing the muscle-cramping pains of Irukandji envenomation, and, although they reduce hypertension and ischaemic myocardial pain, there is no correlation or evidence that they prevent pulmonary oedema or myocardial injury. The assumption that the Queensland Ambulance Service (QAS) introduced this treatment after our trial is incorrect. The QAS Medical Director will confirm that it was introduced independently of our trial and actually before we treated our first case. While pain causes hypertension, in our Patient 1 effective analgesia had been attained without any effect on his hypertension. Also, many patients with Irukandji syndrome have pain without hypertension, while others have severe hypertension even with effective pain control.1 Further evidence that the venom from Carukia barnesi is a sodium channel modulator has been submitted for publication (Ken Winkel, Director, Australian Venom Research Unit, Melbourne, personal communication). Carukia barnesi has now been caught in the Mackay region, 400 kilometres south of Townsville (identified by me, and confirmed by L A Gershwin, PhD student in cubozoan taxonomy, James Cook University, 2003, personal communication). A number of other species can cause the Irukandji syndrome, but the jellyfish causing the sting is rarely caught, so cause and effect are hard to establish at present. Our aim was to present early evidence that sublingual nitrates may be effective in reducing the hypertension that occurs in some cases of Irukandji syndrome; our suggestion was that they be further trialled.2 It seems worthwhile to do so, especially as sublingual nitrates have also been shown to be effective in dysreflexia from spinal injury,3 where hypertension also occurs from the massive release of similar catecholamines. At least two deaths have occurred after Irukandji envenomation, both as a result of cerebrovascular accidents from severe hypertension.4 When treating a patient with severe hypertension from Irukandji envenomation in a prehospital situation, it is reasonable to try to reduce the hypertension. Doing so might reduce the risk of a cerebrovascular accident and possible death, and so further trials of this prehospital treatment must take place. Other prehospital treatments must also be trialled, especially those for pain. Early promising leads need to be published early for all to evaluate. The Irukandji syndrome is a dreadful experience for the victim; all possible prehospital relief measures must be tried and evaluated.

Peter J Fenner