Cardiovascular diseases

The findings of two major trials show that rhythm control is not necessarily superior to rate control There are two broad strategic options in managing recurrent or persistent atrial fibrillation (AF). They are: Rhythm control, in which treatment is directed toward restoring and maintaining sinus rhythm; and Rate control, in which AF is allowed to continue or recur unimpeded, and medications are given to control ventricular rate.1 It has been a widely held and natural assumption that rate control is inferior to rhythm control. Theoretically, the advantages of maintaining sinus rhythm should include fewer thromboembolic complications, reduced need for anticoagulation, and less cardiac failure. In short, fewer deaths and fewer symptoms. However, antiarrhythmic medications have only modest efficacy for preventing AF recurrences, both symptomatic and asymptomatic, so rate-controlling and anticoagulant drugs must also be used in many patients being treated primarily for rhythm control. Also, antiarrhythmic medications can have serious side effects, including life-threatening proarrhythmia and, in the case of the commonly used drug amiodarone, pulmonary fibrosis, thyroid dysfunction and hepatic toxicity. Until recently, few randomised trial data have been available to gauge the extent to which these practical deficiencies offset the potential benefits of rhythm control.2 Now, two major trials comparing the two treatment strategies have been published.3,4 The larger AFFIRM trial was conducted in North America, with all-cause mortality its primary endpoint.3 The smaller trial was conducted in the Netherlands, and had a composite primary endpoint which included heart failure, thromboembolism, bleeding, need for pacemaker implantation, death from cardiovascular causes, and other severe adverse effects of drugs.4 The primary finding in both trials was that rate control was not inferior to rhythm control, and that there were some trends towards superiority of rate control. In the AFFIRM trial, 5-year mortality was 21.3% for rate control versus 23.8% for rhythm control (P = 0.08). In the Dutch trial, the primary endpoint occurred in 17.2% (rate control) versus 22.6% (rhythm control), also narrowly failing to reach conventional significance. For the patient populations studied (minimally symptomatic; mean age, 69 ± 9 years; most with at least one prior episode of AF), these findings indicate that the benefits of the rhythm-control strategy do not, in general, outweigh the risks. What drugs were used? In AFFIRM, by physicians' choice, amiodarone was used in 38% of patients being treated for rhythm control initially, and in 63% at some time in the trial. Sotalol was used in 31% initially, and 41% at some time. Other drugs, including propafenone, procainamide, quinidine, flecainide, disopyramide, moricizine and dofetilide were each used in less than 10% of patients. In the Dutch trial, sotalol was used initially, but replaced (if AF recurred within six months) by propafenone or flecainide, and then, if necessary, by amiodarone. Warfarin treatment could be stopped at the physician's discretion when sinus rhythm had apparently been maintained for four weeks after cardioversion. The detailed outcomes quantify the impact of shortcomings of these antiarrhythmic agents. Sinus rhythm was present in 62.6% (AFFIRM) and 39% (Dutch), respectively, of patients being treated for rhythm control at the conclusion of the trials. The proportion of patients taking warfarin remained above 70% in the AFFIRM study, and above 86% in the Dutch trial. Most disappointingly, the strategy failed to reduce the rates of stroke, other thromboembolic complications, or haemorrhages compared with rate control (see Box). Of the 80 ischaemic strokes incurred in the AFFIRM trial's rhythm-control arm, 55% occurred after discontinuation of warfarin. A further 21% occurred during warfarin treatment, while patients' international normalised ratios (INR) were < 2.0. Only 31% had AF at the time of their stroke. These findings suggest that it may be unsafe to stop anticoagulation for AF patients treated with a rhythm-control strategy, unless there are no other risk factors for stroke (age > 60, previous stroke or transient ischaemic attack, hypertension, rheumatic valve disease, diabetes, cardiomyopathy, planned or recent cardioversion) and/or maintenance of sinus rhythm has been demonstrated not only by lack of symptoms, but also by appropriate ambulatory ("Holter") monitoring.1,5,6 The rate-control arms had significantly lower rates of severe adverse effects attributable to medications — effects such as torsade de pointes, resuscitated cardiac arrest due to bradycardia or pulseless electrical activity, and various non-cardiac adverse events (see Box). The incidence of congestive cardiac failure was non-significantly lower in the rate-control arms in both trials. In subgroup analyses of the AFFIRM trial, rate control had lower risk of death for patients older than 64 years, those without pre-existing congestive cardiac failure, and those with coronary artery disease. A trend in favour of rate control in patients with hypertension in the AFFIRM trial is supported by superiority (primary endpoint 17.3 % v 30.8% for rhythm control) in the corresponding subgroup analysis of the Dutch study. These two trials do not spell the end for electrical cardioversions and antiarrhythmic medications in the management of AF. They concentrated on older, high-risk patients, excluding or under-representing some subgroups of patients who experience AF, for example: patients considered unsuitable for one of the strategies (eg, those with hypertrophic cardiomyopathy, those too symptomatic in rate-controlled AF, or those at unacceptably high risk of bleeding with anticoagulation); and patients under 65 years of age and with no other risk factors for stroke or death. For many such patients, and for most patients' first episode of persistent AF, it remains appropriate to cardiovert once, with a level of anticoagulation appropriate to the patient's risk–benefit profile for some weeks or months, meanwhile treating any concomitant predisposing conditions (congestive heart failure, lung disease, etc), and then review. Many issues need to be considered when deciding and revising optimal treatment in an individual patient. In selected individuals, potentially curative non-pharmacological treatments (eg, pacing,7 catheter ablation,8,9 or maze operation10) may be appropriate. However, for patients represented in the AFFIRM and Dutch trials, a line in the sand has been redrawn. Rate control is safe and should not be considered inferior to rhythm control for minimally symptomatic patients in whom AF is considered likely to recur after cardioversion, particularly if they are older than 64, or have coronary artery disease or hypertension. Healthcare professionals should make assiduous efforts to help patients maintain their INR between 2.0 and 3.0 continuously, and to achieve adequate rate control (defined for the AFFIRM trial as resting rate ≤ 80 beats per minute, and either a 6-minute walk test with a rate ≤ 110, or a 24-hour Holter recording with average rate ≤ 100 and no individual rate more than 110% of the predicted maximum).11 Summary of the findings of two major studies examining rate control and rhythm control in atrial fibrillation AFFIRM3 Dutch study4 Number of participants 4060 522 Mean duration of follow-up 3.5 years 2.3 years Mean age at baseline 70 years 68 years Females 39% 36% Event Rate Rhythm Difference significant? (P ) Rate Rhythm Difference significant? Primary endpoint* 21.3% 23.8% No (0.08) 17.2% 22.6% No Congestive heart failure 2.1% 2.7% No (0.58) 3.5% 4.5% No Thromboembolism 5.5% 7.9% No Cerebral 5.5% 7.1% No (0.79) Other systemic 0.5% 0.4% No (0.62) Pulmonary 0.1% 0.5% No (0.16) Haemorrhage 4.7% 3.4% No Primary intracerebral 1.1% 1.3% No (0.73) Subdural or subarachnoid 0.8% 0.8% No (0.68) Non-central nervous system 7.7% 6.9% No (0.44) Severe adverse effects of drugs (other than anticoagulants) 0.8% 4.5% Yes Torsades des pointes 0.2% 0.8% Yes (0.007) Resuscitated cardiac arrest due to bradycardia or pulseless electrical activity < 0.1% 0.6% Yes (0.01) Pulmonary events† 1.7% 7.3% Yes (< 0.001) Gastrointestinal events† 2.1% 8.0% Yes (< 0.001) Bradycardia† 4.2% 6.0% Yes (0.001) Prolongation of corrected QT interval (> 520 ms)† 0.3% 1.9% Yes (< 0.001) Other adverse events† 14.0% 25.4% Yes (< 0.001) * All-cause mortality for the AFFIRM trial,3 and a composite primary endpoint which included heart failure, thromboembolism, bleeding, need for pacemaker implantation, death from cardiovascular causes, and other severe adverse effects of drugs for the Dutch trial.4 † Prompting discontinuation of a drug.

Michael J Kilborn FRACP, DPhil

Objective: To describe the levels of inflammation and vascular endothelial activation in an Aboriginal community, and the relationship of these factors to coronary heart disease (CHD) risk factors and markers of nutritional quality.Design and participants: A cross-sectional survey of 95 women and 76 men participating in a chronic-disease prevention program.Setting: A remote Aboriginal community in Western Australia in 1996.Main outcome measures: Concentrations of markers of inflammation (C-reactive protein [CRP]) and vascular endothelial activation (soluble E-selectin [sE-selectin]); presence of metabolic syndrome; concentrations of diet-derived antioxidants.Results: Participants exhibited very high plasma concentrations of CRP (mean, 5.4 mg/L; 95% CI, 4.6–6.3 mg/L) and sE-selectin (mean, 119 ng/mL; 95% CI, 111–128 ng/mL). Both CRP and sE-selectin concentrations were significantly higher in the presence of the metabolic syndrome. There were significant inverse linear relationships between concentrations of CRP and plasma concentrations of the antioxidants lycopene, β-carotene, cryptoxanthin and retinol. Even stronger inverse associations were evident between concentrations of sE-selectin and lycopene, β-carotene, cryptoxanthin and lutein.Conclusions: Vascular inflammation and endothelial activation may be important mediators of elevated CHD risk in Aboriginal people. Inadequate nutrition and physical inactivity may contribute to this process.

Kevin Rowley BAppSci PhD · Jacob Cohen BSc · Alicia J Jenkins FRACP FRCP · David O'Neal MB BS, MD, FRACP · James D Best FRACP FRCPath · Karen Z Walker PhD MND · Qing Su MSc PhD · Kerin O'Dea BSc PhD

Formal risk-based protocols and clinical audits of process indicators and outcomes are needed "Missed" myocardial infarction occurs when a patient with an unrecognised acute coronary syndrome is discharged from hospital prematurely. The correct diagnosis becomes apparent only when the patient has an infarct or cardiac arrest, or is later found to have biochemical evidence of myocardial injury. There has been a paradigm shift in management of patients with chest pain over the past decade, with the focus moving from establishing a diagnosis towards ensuring the safety of the management strategy. This change was heralded by the publication of Australian guidelines in 1996 that recommended: Initial risk stratification of patients using clinical variables; Admission of intermediate- and high-risk patients for 48 hours of clinical observation to identify those with recurrent ischaemia at rest or evidence of myocardial damage (raised levels of cardiac biomarkers or electrocardiogram [ECG] changes); and If these features are absent, stress testing to exclude exercise-induced ischaemia in all remaining patients before discharge.1 Studies in the United States showed that the period of observation can be shortened to eight hours without affecting patient outcomes.2,3 Management guidelines were updated accordingly.4 Missed myocardial infarction usually results from a breakdown in the system of care — the patient's risk has been underestimated or formal protocols have not been fully implemented. Two studies in this issue of the Journal provide excellent examples of hospital strategies to improve the safety of chest pain triage. Aroney and colleagues (page 370) demonstrate that implementation of a protocol adhering to current Australian guidelines4 minimises missed myocardial infarction.5 They provide a benchmark for other hospitals to compare their practice. Boufous and colleagues (page 375) show that local implementation strategies can reduce medical error which contributes to missed myocardial infarction.6 A new "gold standard" for care. Aroney et al describe an "accelerated chest pain assessment protocol" that minimised hospital stay without jeopardising patient safety.5 After identifying intermediate-risk patients, they implemented a rapid, two-step process to ultimately identify those who were low risk and suitable for early discharge. They shortened the period of observation to a minimum of six hours. The absence of a single infarct in the 409 patients classified as low risk is an excellent outcome, clearly confirming the safety of the protocol. Of interest, 11% of the study population had diabetes but were safely triaged by the protocol. Thus, the recent recommendation to classify all patients with diabetes as high risk may not be necessary. Validation of new markers of increased risk, such as C-reactive protein, may allow risk-stratification algorithms to be further refined.7,8 Aroney et al achieved their outcomes in a large teaching hospital where coronary care nurses and "on-call" cardiology registrars were used to implement weekend stress testing, the final step in risk stratification before discharge. As many Australian hospitals have fewer resources, it is worth identifying non-essential elements of the protocol. The study data allow limited assessment of the incremental value of each step in the protocol, excluding the 78 patients who were unable to perform an exercise test. Most of the remaining 142 at-risk patients were identified by clinical, ECG or cardiac biomarker findings. Continuous ST-segment monitoring detected less than 2% of at-risk patients. As this monitoring is expensive, its use is difficult to justify in smaller hospitals. On the other hand, 42 at-risk patients (30%) were identified by an exercise ECG. Thus, this test should not be omitted. Coronary angiography was recommended in high-risk patients, but was performed in only 41%, as many were frail or had significant comorbidities. It is interesting to speculate whether outcomes in this group could have been improved by attention to optimal medical therapy and routine stress imaging. Are patients selected appropriately? Aroney et al do not report the numbers and outcomes of patients who were classified as low risk at initial clinical assessment and who were therefore not included in the study. Some at-risk patients may have been misclassified and discharged prematurely, predisposing them to missed myocardial infarction. Boufous et al audited this phenomenon.6 Their method was imperfect, as the reviewing cardiologist had to rely on the original clinical records. Despite this reservation, it is reassuring that formal adoption and use of a risk-stratification algorithm by clinical staff halved the rate of inappropriate discharge from 20% to 10%. Nevertheless, some potentially at-risk patients were discharged against current guidelines. The study was too small to detect an impact on their outcomes, and, to my knowledge, there are no published data on outcome in this group. However, the value of such a study is illustrated by an eight-month audit of emergency chest pain triage performed at my institution five years ago. Using a risk-stratification algorithm, we identified 136 intermediate-risk patients who were discharged contrary to guidelines. In most cases, patients were observed for at least eight hours, and serial biomarkers were measured. The guideline violation was primarily a failure to perform exercise stress testing, either because it was not available or because there was no in-patient bed to hold the patient until the test could be performed. Outcome was determined in all patients at one month. One death (documented ventricular fibrillation after recurrent chest pain) and five myocardial infarctions occurred during this period: three of these events, including the death, occurred within 24 hours of discharge. While the outcome for this group of patients was not statistically different from the outcome in 116 patients managed appropriately and discharged within 24 hours (one missed myocardial infarction), the clinical significance of the data persuaded our hospital managers to fund exercise stress testing on weekends. Coupled with an education program and a protocol similar to that described by Aroney et al, we subsequently reduced our underadmission rate substantially. How can hospitals improve triage of chest pain? It is unlikely that there will ever be high-level evidence to guide chest pain triage. As outlined above, poor outcomes such as missed myocardial infarction arise through medical error or inadequate resources, and the changes required to conduct a randomised trial would reduce the likelihood of the former and, by ethical necessity, ensure the latter. In the absence of high level evidence, hospitals should adopt methods to improve clinical practice,9,10 such as strategies similar to those described by Aroney and Boufous. Risk stratification and standardised protocols can reduce medical error, as shown by Boufous et al.6 To optimise bed use, all hospitals should adopt accelerated chest pain assessment protocols similar to that described by Aroney et al.5 Lack of stress testing, particularly at weekends, is the major impediment to their widespread adoption. To inform local resource allocation, hospitals should audit indicators of process, such as appropriate risk stratification and underadmission of at-risk patients. They should also measure patient outcomes, and, if these outcomes do not match those of Aroney et al, then hospitals should revise their current management strategies.

M Andrew Fitzpatrick MD FRACP

Infarct angioplasty has the potential to increase the disparity in outcomes between rural and urban patients with myocardial infarction The need for rapid treatment of coronary syndromes has been recognised for many years. Despite recent emphasis on the benefits of rapid thrombolysis, the main advantage of early presentation remains resuscitation from ventricular fibrillation. Defibrillation has been estimated to save about six times as many lives as thrombolytic treatment,1 but patients must reach medical assistance in time for it to be effective. On average, patients delay more than an hour before seeking help for symptoms of acute myocardial infarction, and about another hour elapses before they arrive at hospital.2-4 Attempts to shorten patient delay by education campaigns have been generally ineffective5 and, in recent years, efforts have been mainly directed towards expediting transport and hospital treatment of patients with myocardial infarction.2,3,6 In Australia, these efforts include fast-track pathways and delivering thrombolysis in emergency departments, before cardiological review.2,7 Significant improvements in call-to-needle times have been achieved,6 but, as Kelly and colleagues document in this issue of the Journal (page 381),2 not all patients are treated as rapidly as is desirable. The study by Kelly et al is particularly useful because it includes many of the patients treated with thrombolysis in Victoria over their study period of 30 months, and includes patients from rural and urban regions. Their data show that patients from rural areas delay longer before seeking attention and are slower to receive treatment than patients from large urban areas. While the association between delay in treatment and increased mortality in this study is likely to be partly confounded by unmeasured variables, few would dispute that these delays increase infarct size and the likelihood of dying during and after hospitalisation. Delayed treatment of myocardial infarction is one more manifestation of the geographic gradient in healthcare and outcomes in Australia.8 Controlled trials have shown that prehospital thrombo-lysis reduces mortality by about 20%.9 Prehospital thrombolysis is particularly suitable for remote regions with long ambulance transport times, and has been successfully implemented overseas without the use of mobile intensive care units.10 Even in urban areas, significant reductions in treatment delay have been achieved (between 30 and 60 minutes9), perhaps partly because a diagnosis is established before patients arrive at hospital and the hospital assessment process is circumvented. Yet, in Australia, prehospital thrombolysis has not been implemented in a systematic way. Kelly et al identify many of the barriers to the use of prehospital thrombolysis, including lack of appropriate ambulance equipment and failure to train and empower paramedics and nurses to give thrombolysis.2 They argue for a "bottom up" approach where individual healthcare ser-vices develop and own their strategies. Unfortunately, by itself, this is unlikely to effect change because of the complex funding mix of healthcare services in Australia and the parlous financial state of many rural health services. While rural and regional centres struggle to treat patients expeditiously with limited resources, metropolitan hospitals with cardiac catheterisation laboratories are moving steadily towards infarct angioplasty instead of thrombolysis.11 Whether this proceeds on a 24-hour basis depends mainly on the ability of individual cardiology departments to corral the necessary resources from their hospitals and the willingness of their staff to work nights and weekends. There is a strong body of evidence showing that infarct angioplasty is a better treatment than thrombolysis,12 but it is certainly more expensive to institute upfront. Proponents argue that it is cost effective compared with thrombolysis as it reduces hospital stay, but experience has taught hospital administrators to be wary of these claims as they rarely result in real cost savings. However, there is little doubt that infarct angioplasty is here to stay and that it will improve outcomes from myocardial infarction in patients fortunate enough to have access to it. If current trends continue, it has the potential to further increase the disparity in outcomes between rural and urban patients with myocardial infarction. How then should we respond to the data provided by Kelly and colleagues? Time delays in administering thrombolysis need to be seen in the context of the emergence of widespread use of infarct angioplasty and the particular geographic difficulties imposed by the Australian setting. In areas with transport times of more than 20 minutes, systematic use of prehospital thrombolysis could substantially improve outcomes at a modest cost. In urban areas, rapid transit to a facility with the ability to perform percutaneous transluminal coronary angioplasty (PTCA) is likely to become the standard. A combination of the two strategies could also be trialed in patients from areas without rapid access to PTCA (so called facilitated infarct angioplasty). Finally, in the debate about how best to achieve early revascularisation, it should not be forgotten that most of the delay occurs before the patient contacts the ambulance service and that, in this period, death is usually the result of ventricular fibrillation. As no strategy has been identified that encourages patients to present earlier, research should be directed towards improving the treatment of cardiac arrest with interventions such as prehospital thrombolysis13 and public access defibrillators.14

James W Leitch MB BS, FRACP

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months.Design: Prospective clinical audit.Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features.Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines — 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand.Main outcome measure: Adverse cardiac events during six-month follow-up.Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%).Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Con N Aroney MD, FRACP · Heather L Dunlevie BHlthScN · JH Nicholas Bett FRACP

Objective: To evaluate the impact of a chest-pain guideline on clinical decision-making and medium-term outcomes of patients presenting to a hospital emergency department (ED) with non-traumatic chest pain.Design: Before-and-after guideline implementation study.Setting: Bankstown–Lidcombe Hospital, Sydney, NSW (454-bed metropolitan teaching hospital), in the six-month periods before and after guideline implementation in February 2001.Participants: Patients presenting to the ED with non-traumatic chest pain who had chest-pain assessment forms completed by ED doctors, comprising 422/768 (54.9%) of those presenting before and 461/691 (66.7%) after guideline implementation.Main outcome measures: Appropriateness of admission/discharge decisions compared with decision of senior cardiologist based on guideline; death, recurrent chest pain, ED re-presentation and hospital readmission in the ensuing three months.Results: After guideline implementation, appropriate admission/discharge decisions increased significantly from 180/265 (68%) to 261/324 (81%) (difference, 13%; 95% CI, 6%–20%). The largest increase was for patients at moderate risk of death or acute myocardial infarction within six months, from 39/96 (38%) to 57/103 (55%) (difference, 18%; 95% CI, 4%–31%). Increases were seen for both junior doctors (interns and resident medical officers) (18%; 95% CI, 7%–30%) and senior doctors (11%; 95% CI, 2%–19%). Logistic regression showed that implementation of the guideline, seniority of assessing doctor and patient history of coronary disease were independent predictors of appropriate decisions. There was a significant decline in re-presentations to ED with recurrent chest pain in patients previously presenting with cardiac or possibly cardiac pain, from 46/201 (23%) before implementation to 32/247 (13%) after (difference, 210%; 95% CI, 217% to 23%).Conclusions: The chest-pain guideline resulted in a significant improvement in clinical decision-making in the ED and reduced re-presentations with cardiac/possibly cardiac chest pain.

Soufiane Boufous MPH(Hons) · Bin B Jalaludin PhD, FAFPHM · Charles H Pain FAFHPM · Susan Ieraci FACEM · Anne-Louise Gray BAppSc, PGCertMgt · Susan E Harris B Phty, MPH · Craig P Juergens FRACP · Peter W Kelleher FRACP · Linda M Dann FANZCA, FACEM

Objective: To determine the proportion of patients in Victoria treated within the British Heart Foundation 90-minute call-to-needle (CTN) time benchmark for thrombolysis of ST-elevation myocardial infarction (STEMI), and to validate the British Heart Foundation 90-minute benchmark with respect to mortality.Design: Cohort study.Setting: 20 hospitals and two ambulance services in the State of Victoria, Australia.Participants: 1147 patients with STEMI transported to hospital by ambulance and eligible for thrombolysis.Main outcome measures: CTN time, and in-hospital mortality.Results: Median CTN time was 83 minutes (mean, 93.2 min; range, 29–894 min). Median door-to-needle (DTN) time was 37 minutes (mean, 46.5 min; range, 0–853 min). 61% of patients received thrombolysis within the 90-minute benchmark. Patients with CTN times > 90 minutes had an increased risk of dying (relative risk, 1.8; 95% CI, 1.3–2.7). Factors associated with CTN time < 90 minutes were lower DTN time, prior notification of the receiving hospital and transport time less than 20 minutes.Conclusion: The British Heart Foundation CTN time benchmark is being met for 61% of eligible STEMI patients in Victoria. Strategies to reduce CTN time should be region-specific, and should include attempts to reduce DTN and to enhance ambulance–hospital communication. Prehospital thrombolysis may be appropriate for some regions.

Anne-Maree Kelly MD, FACEM · Debra Kerr BN, MBL · Ian Patrick BParamedStud, MICAcert · Tony Walker BParamedStud, GDipEd

An Expert Working Group of the National Heart Foundation of Australia undertook a review of systematic reviews of the evidence relating to major psychosocial risk factors to assess whether there are independent associations between any of the factors and the development and progression of coronary heart disease (CHD), or the occurrence of acute cardiac events. The expert group concluded that (i) there is strong and consistent evidence of an independent causal association between depression, social isolation and lack of quality social support and the causes and prognosis of CHD; and (ii) there is 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 disorders and CHD. The increased risk contributed by these psychosocial factors is of similar order to the more conventional CHD risk factors such as smoking, dyslipidaemia and hypertension. The identified psychosocial risk factors should be taken into account during individual CHD risk assessment and management, and have implications for public health policy and research.

Stephen J Bunker PhD, RN · David M Colquhoun MB BS, FRACP · Murray D Esler PhD, FRACP · Ian B Hickie MD, FRANZCP · David Hunt FRACP, FACC · V Michael Jelinek FRACP, FACC · Brian F Oldenburg PhD, MPsychol · Hedley G Peach PhD, FFPHM · Denise Ruth FRACGP, FAFPHM · Christopher C Tennant MRCPsych, FRANZCP · Andrew M Tonkin MD, FRACP

To the Editor: The publication of the main results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), and the accompanying editorial, triumph the role of thiazide diuretics as first-line management for hypertension.1,2 It brought to mind the lines from the nursery rhyme Old Mother Hubbard — "And when she went there, the cupboard was bare." Simple frequency analysis of diuretic antihypertensive medications listed in the Australian Medicines Handbook (1998 and 2003) revealed that the total number of thiazide diuretics available as monotherapy in 1998 was six (bendrofluazide chlorothiazide, chlorthalidone, hydrochlorothiazide, methyclothiazide and indapamide), and in 2003 three (bendrofluazide, chlorthalidone and indapamide).3,4

Mark R Nelson

To the Editor: Kuchar et al1 describe a patient who received an implantable defibrillator discharge after a single ingestion of loratadine. We are concerned that their conclusion — that this patient "probably" had drug-induced torsade de pointes — is incorrect. Review of the intracardiac electrograms from this patient (shown in Box 2 of their article) with known monomorphic ventricular tachycardia (VT; shown in their Box 1) shows a relatively fixed rate of the VT without the large variations in cycle length consistent with torsade de pointes. While there are no established guidelines for determining torsade de pointes based on intracardiac electrograms, it is clear that during monomorphic VT electrocardiograms can show variability in amplitude and orientation. Consistent with the early stages of monomorphic VT,2 the first three electrograms have a different orientation compared with the remaining electrograms, which are largely similar. Unfortunately, as the transition from supraventricular rhythm to tachycardia was not shown, it cannot be ascertained whether the tachycardia began with a pause-dependent mechanism, an important criterion to help diagnose torsade de pointes.3 Given that this patient's implantable defibrillator intracardiac electrograms do not show a continually changing electrogram pattern, that the cycle length is relatively constant, and that there is a lack of documented QT prolongation, there is no evidence of the patient's arrhythmia being torsade de pointes. Incidentally, it is unclear whether these electrograms were recorded before (as specified in the discussion) or after defibrillator discharge (title of Box 2). It is well documented that a defibrillator discharge can have significant effects on the recording of intraventricular electrograms. Most likely, this patient, with documented pre-existing monomorphic VT (their Box 1[b]), had an episode of VT (not torsade de pointes) appropriately treated by the implanted defibrillator, probably having no direct relationship with loratadine. Notably, their Box 3 shows torsade de pointes in another patient, not receiving loratadine. In summary, Kuchar et al1 correctly state that there have been no documented episodes of torsade de pointes after ingestion of loratadine. Similarly, their report does not appear to document an episode of torsade de pointes.

Philip T Sager · Enrico P Veltri

In reply: We agree that there are no guidelines defining torsade de pointes based on intracardiac electrograms, but there are several reasons why the likelihood of torsade de pointes (as opposed to any other arrhythmia) in our patient is high. The electrogram shows the arrhythmia just before delivery of direct current shock, this being about 30 minutes after the patient took her first ever dose of loratadine. There are marked variations in electrogram morphology, despite minimal variation in RR interval, in a short strip of recording in this patient with documented QT prolongation. Further, she had no history of monomorphic ventricular tachycardia, no inducible monomorphic ventricular tachycardia at electrophysiologic examination, and no evidence of structural heart disease. Neither was a mechanism for supraventricular arrhythmia identified. The absence of initiating beats showing pause-dependence is unfortunate, but this is not provided by the generation of device implanted in this patient. Hence, we believe the word "probable" is an apt description for the observation made.

Dennis L Kuchar · Bruce D Walker · Charles W Thorburn

Measurement of clinical performance. Practical approaches in acute myocardial infarction. Robert West, Robin Norris (editors). London: Royal College of Physicians, 2001 (viii + 128 pp). ISBN 1 86016 152 9. Evaluating the quality of clinical care is now the accepted, indeed mandatory, duty of all who practise medicine. Medical colleges have introduced programs for maintaining professional standards, and many of these feature clinical audit as a necessary activity. For the busy clinician, however, finding both the time and the means to perform accurate and consistent audits poses major challenges. This work, from the Royal College of Physicians (RCP), offers pragmatic strategies at both a national and a local level for conducting meaningful clinical audit. While focusing on the care of patients with myocardial infarction, the messages contained in this book can apply to any area of medicine. The first half deals with clinical governance (UK style): use of performance indicators and league tables; the choice between process or outcome measures; and an overview of national benchmarking projects in the UK dealing with coronary heart disease, asthma and stroke. The second half covers the practicalities of auditing the care of patients with myocardial infarction, as exemplified by the Myocardial Infarction National Audit Project. This ambitious project aims to recruit all hospitals in England and Wales, and uses a nationally funded, RCP-sponsored data collection, analysis and reporting system which is standardised, computer-based and centrally coordinated. Such a system relieves local clinicians of the need to develop their own audit system from the ground up. The authors of each chapter speak authoritatively from personal experience about the good and bad in conducting clinical audit, and offer advice on what to avoid. Finding a "how to" book in performance measurement that is short (128 pages), easy to read, inexpensive and rich in practical applications is a rare delight for this jaded healthcare researcher. My only regret — I would have liked a little more on how to use the results of audit to full effect in improving quality of care at the local level. Ian A ScottDirector of Internal Medicine Princess Alexandra Hospital, Brisbane, QLD

Ian A Scott

We need to derive absolute cardiovascular risk functions based on contemporary Australian data The accurate estimation of risk for future disease events is critical to the determination of the benefit–risk ratio and the most cost-effective use of preventive therapies (Box 1). This is particularly relevant for cardiovascular diseases (CVD), which are the leading cause of deaths in Australia (40% of total deaths), and in 1993–1994 accounted for the largest proportion (12%, or $3.9 billion) of total annual recurrent health expenditure.3 (This proportion is now almost certainly greater.) Expenditure on cardiovascular drugs under the Pharmaceutical Benefits Scheme totals $1.2 billion annually, $629 million of this on lipid-lowering drugs, especially statins.4 Accurate assessment of the likelihood of future events would optimise resource allocation by targeting patients at higher risk.5 In this context, the work of Simons et al, reported in this issue of the Journal (page 113),6 is very important. In their ongoing Dubbo Study (which commenced in 1988 and involved 2805 men and women aged 60 years and older when first assessed), the authors evaluated a risk function for coronary heart disease (CHD) prediction developed from a longitudinal cohort study in Framingham, Massachusetts — the Framingham Study. They also derived a risk function for future CVD events, including stroke as well as CHD, by modelling data from the Dubbo cohort. The Framingham risk functions7-9 are widely used and form the basis of a New Zealand cardiovascular risk calculator,10 itself proposed as the absolute risk measurement tool in the recent lipid guidelines of the National Heart Foundation/Cardiac Society of Australia and New Zealand.11 The Framingham cohort consists primarily of white, middle-class individuals. The equation was derived from calculations based on age, sex, cigarette smoking status, diabetes status, and blood pressure, cholesterol and HDL cholesterol levels only. The Framingham measurements were also made some time ago before the dramatic increase in the prevalence of diabetes,12 and indeed Framingham included low numbers of people with diabetes. In essence, the study by Simons et al determined the applicability of observations made in another time and another place to an Australian population. They showed that the Framingham equation accurately predicted overall 10-year incidence of "hard" CHD endpoints (myocardial infarction or coronary death). This supports previous validation work with the Framingham equation in the Busselton study.13 However, the Busselton study is now over 20 years old, while the Dubbo cohort included only older individuals. Therefore, while these validation studies are important, it would be more relevant to derive predictive equations from data obtained from a representative and contemporary Australian cohort. This would acknowledge the variety of ethnic groups in Australia and the current mix of known and unknown risk factors. As the Framingham equation correctly predicts risk in only about 80% of cases,14 there is considerable interest in "novel" risk factors (eg, high sensitivity C-reactive protein) and techniques for imaging the arterial wall. Future research must examine the degree to which these elements might improve the ability to correctly identify those at risk. With the shift of treatment guidelines from individual risk thresholds for treatment to decisions based on multivariable absolute risk, the logical extension of this is to estimate treatment efficacy or effectiveness in terms of absolute treatment benefit. For example, the benefits of cholesterol lowering in terms of improving average life expectancy have previously been estimated.15 This approach would provide more meaningful information to both patients and clinicians, as well as allowing the non-cardiovascular benefits of modifying risk factors such as tobacco smoking, physical inactivity, and unhealthy diet to be taken into account. Data such as those from the Dubbo study have important implications for current Australian guidelines and practice (Box 2). Treatment decisions based on individual risk-factor thresholds are inadequate. The Dubbo study assesses the validity of the Framingham risk prediction equations in the elderly and provides an Australian risk equation for the same age group. Further work should be done to validate these equations in a wider contemporary population and to determine the extent to which new risk factors may improve assessment of risk. This should not, however, preclude swift measures to implement the use of absolute risk, as well as consideration of absolute treatment benefit, as ways of guiding treatment decisions in clinical practice. 1: Why focus on absolute risk of cardiovascular disease? Individuals with levels which fall in the highest decile for systolic blood pressure, cholesterol and body mass index account for only 20%–30% of the total number of cases of stroke, ischaemic heart disease and diabetes.1 Interventions based on elevated levels of a single risk factor may allocate treatment to individuals with little chance of gain because of low absolute risk.2 Absolute risk is the likelihood of developing an event(s) over a particular time period. Absolute risk equations acknowledge the multifactorial causation of cardiovascular disease, the sex difference in risk and the steep increase in risk with ageing. Epidemiological studies have shown a continuum of risk for increasing levels of risk factors, such as blood pressure, total cholesterol and HDL cholesterol levels, which is acknowledged in absolute risk equations. 2: Recommendations for current guidelines, practice and research in cardiovascular disease Treatment guidelines should place greater emphasis on absolute risk estimation in those without manifest cardiovascular disease (CVD). Linking estimates of the likely absolute benefit of interventions with calculation of absolute risk should reinforce the rationale for lifestyle measure for all individuals and pharmacological treatment for those at higher risk. Prediction of overall CVD risk over 5 (or 10) years should be the endpoint, as opposed to risk of coronary heart disease alone. Components of a composite CVD endpoint should be re-examined and possibly restricted to "hard" outcomes such as CVD death, non-fatal myocardial infarction and non-fatal stroke. Agreement on and adoption of a standardised approach would facilitate implementing absolute risk prediction in Australia. Future studies should include variables that might further improve risk prediction (eg, waist circumference, microalbuminuria, high-sensitivity C-reactive protein). Absolute risk assessment is likely to be implemented most effectively using electronic tools which can link to other national initiatives. Absolute risk assessment will not only optimise health gains, but will result in more cost-effective treatment and prevention.

Andrew M Tonkin MB BS, MD, FRACP · Stephen S Lim BA, BSc · Henrik Schirmer MD, PhD

Objectives: To evaluate a Framingham risk function for coronary heart disease in an elderly Australian cohort and to derive a risk function for cardiovascular disease (CVD) in elderly Australians.Design and setting: Analysis of data from a prospective cohort study (the Dubbo Study) in a semi-urban town (population, 34 000).Participants: 2805 men and women 60 years and older living in the community, first assessed in 1988, and a subcohort of 2102 free of CVD at study entry.Main outcome measures: Incidence of CVD (myocardial infarction, coronary death or stroke) over 5 and 10 years.Results: A Framingham risk function assessing "hard" coronary heart disease (ie, myocardial infarction or coronary death) accurately predicted 10-year incidence in men and women aged 60–79 years who were free of prevalent CVD or diabetes at study entry. In a multiple logistic model, CVD incidence was significantly predicted by age, sex, taking antihypertensive medication, blood pressure, smoking, total cholesterol level and diabetes. For a given age and cholesterol level, CVD risk over 5 years was doubled in the presence of antihypertensive medication or diabetes, increased by 50% with cigarette smoking, and halved in women compared with men.Conclusions: We have derived a simple CVD risk function specifically for elderly Australians that employs risk factors readily accessible to all medical practitioners.

Leon A Simons MD, FRACP · Judith Simons MACS · Latha Palaniappan MD, FACP · Yechiel Friedlander PhD · John McCallum DPhil

To the Editor: Interpretation of the report describing the first death attributed to the Irukandji syndrome should be tempered by the fact that significant unstated assumptions have been made in attributing the cause of death to a jellyfish.1 While envenomation by a jellyfish remains the likely diagnostic possibility, no evidence is presented that unequivocally confirms a jellyfish as the lethal agent. Several methods could have been used to support or confirm the diagnosis of jellyfish envenomation, including sampling of nematocysts from the victim's skin (before or after death), jellyfish capture, or reports of other similar, but less severe, stings from the same beach around the time the victim was stung. In severe jellyfish envenomation, attempts are often made to harvest nematocysts from patients' skin, most commonly by skin scraping or by sticky tape sampling.2 Recovered nematocysts may help to identify the species, and confirm the diagnosis.3 Although successful nematocyst recovery is uncommon in Irukandji syndrome, it is disappointing that "no attempt was made to sample nematocysts"1 given the relative simplicity of the procedure and the importance of this case. The authors state that "no sting site was clearly delineated",1 but then go on to say that there were, in fact, areas of "skin flushing and intermittent diaphoresis"1 over a significant period of time. Sticky tape sampling of these areas may have yielded nematocysts, allowing positive species identification. Postmortem skin sections have also been employed in Chironex fleckeri fatalities, and have shown nematocyst barbs on the victim's skin.4 Postmortem examination may also have revealed other contributing factors. I am particularly interested in the assertion that almost every Irukandji syndrome patient in the Whitsundays develops a "rise in cardiac troponin levels".1 In fact, the cited article makes no mention of troponin, simply stating that CK-MB (creatine kinase isoenzyme) levels "can be abnormal",5 and that "some severe cases [of Irukandji syndrome] may have a CK-MB [level] well above the normal range".5 Many aspects of the diagnosis and treatment of jellyfish envenoming remain controversial. Accurate reporting of unusual cases is thus of the utmost importance.

Paul M Bailey

Chlamydia pneumoniae has been detected in atherosclerotic plaques, while seropositivity to this organism confers a slightly increased risk of coronary events. However, no aetiological link has been established; a major difficulty when investigating this link is the lack of a gold standard for diagnosing chronic vessel infection. The outcomes of case–control studies and prospective trials of macrolides in treatment and prevention of cardiovascular disease have been ambiguous but suggest a short-term preventive effect. Whether this is due to the antimicrobial or anti-inflammatory activity of the macrolides is unknown. Larger and longer prospective trials currently under way may provide better insight into the association of C. pneumoniae with cardiovascular disease. At present, there is no justification for treating cardiovascular disease with antibiotics.

Mikkel M Larsen BSc · Birgitte Moern MD, PhD · Paul L Andersen MD, DMSc · Lars J Ostergaard PhD, DMSc · Andrew Fuller FRACP

To the Editor: Advocating implementation of evidence-based clinical practice guidelines is one aspect of the current drive to provide quality healthcare across different centres. Quality theory demands that outcomes are continuously sought and that practices are modified accordingly — the "quality loop". Therefore, Scott and Harper are to be applauded for their pursuit of improved outcomes, not just improved processes, in studying guideline-discordant care in acute myocardial infarction.1 I believe that this type of study, which objectively demonstrates the role of practice guidelines in "real world" practice, is very important. However, as a geriatrician, my patient population is unlikely to intersect with populations enrolled in large cardiology trials (eg, those for thrombolysis in myocardial infarction).2,3 Comorbidities, such as renal impairment, cognitive impairment and poor functional status at baseline, were not explicit exclusion criteria, but, when present, would have reduced an individual's chance of being enrolled. These types of comorbidities are likely to be associated with a reluctance on the part of patients and physicians to pursue life-prolonging interventions. They are also likely to be associated with poorer outcomes, whatever the intervention. Therefore, I believe that these non-cardiac comorbidities are potential confounders for study designs, such as that of Scott and Harper.1 Older age per se has been well studied in the cardiology literature on management of myocardial infarction. However, in the literature on adherence to guidelines, few studies have attempted to fully identify the non-cardiac-related characteristics of those receiving guideline-discordant care. Krumholz et al reported that altered mental state is one factor, and that, of a large "real-world" cohort aged 65 or more, only 8% were considered ideal candidates for thrombolytic therapy.4 Quality healthcare involves multiple dimensions, including both personal and process factors. Practice guidelines are valuable tools to reduce practice variation, but we need to continue to evaluate whether they can be applied as broadly as may be advocated. Surely, evidence-based guidelines can only be confidently applied to situations for which an evidence base exists. It will be important to test the application of guidelines in many settings, with attention to potential confounders, and, in particular, to outcome measures.

Kristen J Pearson

In reply: We thank Pearson for her kind comments and agree the design of our study1 prevented identification of all patient factors that may, quite reasonably, impact on clinicians' decisions to administer specific treatments to older patients with acute myocardial infarction (AMI). These factors may also have precluded such patients from enrolment in clinical trials, the results of which underpin recommendations within clinical practice guidelines. On the other hand, we know advancing age is an independent predictor of increased mortality after AMI, with several possible causes: age-related reductions in protective mechanisms (such as myocardial preconditioning),2 presence of cardiac and non-cardiac comorbidities unaffected by treatments for AMI,3 and — the focus of our study — underuse of effective therapies in the absence of discernible contraindications.4,5 While cognitive impairment, renal dysfunction and poor functional status may dissuade patients and/or clinicians from pursuing "aggressive" management, we have no evidence that these factors, singly or in combination, necessarily attenuate the benefits of specific interventions for AMI in patients at high baseline risk of cardiac death.6 We also adjusted mortality comparisons between concordant- and discordant-care groups for multiple measures of illness severity at presentation which predict a poor prognosis. Nevertheless, we support calls for more randomised trials of treatments for AMI and other conditions in older patients with liberal, "real-world" inclusion criteria in determining absolute risks and benefits of intervention in the presence of multiple comorbidities and impaired function.

Ian A Scott · Catherine M Harper

The 14th World Congress of Cardiology, held in Sydney 5–9 May 2002 (the first time ever in the antipodes), was a joint meeting with the 50th anniversary meeting of the Cardiac Society of Australia and New Zealand (CSANZ). The Congress is the principal meeting of the World Heart Federation, a body comprising all of the world's cardiac societies and heart foundations. Delegates came from 115 countries, and there was a total registration of just over 9000. More than 3000 abstracts were received from investigators in 82 countries. In addition to focusing on developments at the cutting edge of cardiovascular disease, the Congress explored themes such as the world burden of cardiovascular disease and the likely rise of this burden in the 21st century, particularly in developing countries — a prospect of particular concern to the World Heart Federation. Worldwide issuesIschaemic heart disease is the leading cause of death in developed countries. While age-adjusted mortality from the disease is gradually falling in developed countries, including Australia, it is set to become an epidemic in developing countries, and over the next 20 years will probably become the most important global health problem. This was put into perspective by Salim Yusuf (Director of Cardiology, McMaster University, Hamilton, Canada). George Mensah (Head, Cardiovascular Division, Centers for Disease Control and Prevention, Atlanta, USA) highlighted the fact that the epidemic of ischaemic heart disease is driven by tobacco use, particularly in Asian and former Eastern European countries, while Stephen Colagiuri (Director of Endocrinology, Prince of Wales Hospital, Sydney) emphasised the rapid increase in diabetes that is occurring with population aging and increasing overweight and obesity. David Wood (Professor of Preventive Cardiology, National Heart and Lung Institute, London, UK) made the point that both prevention and treatment must translate into practice the large scientific and clinical evidence base of effective measures, but that we should also focus on developing tools to assess future absolute risk of cardiovascular disease rather than concentrating only on individual risk factors. These measures should support compliance with therapeutic regimens (Martha Hill, Dean of Nursing, Johns Hopkins University, Baltimore, USA) and, very importantly, consider the underlying psychosocial and socioeconomic determinants of disease (Michael Marmot, Professor of Epidemiology and Public Health, University College, London, UK), particularly in the vastly populated poor regions of Asia (Sania Nishtar, Director, Heartfile, Pakistan). AtherosclerosisInflammation is now regarded as a key process in the development of atherosclerosis and the destabilisation and rupture of plaques in acute coronary syndromes and cardiac death. The role of activated macrophages and T lymphocytes in secreting matrix metalloproteinases and tissue factor during plaque rupture was highlighted.1 This information has almost immediate practical application: diagnostic assays for inflammatory markers such as C-reactive protein are predictive of risk of myocardial infarction, stroke and death in population studies. Valentin Fuster (Director, Weiner Cardiovascular Institute, Mount Sinai School of Medicine, New York, USA) also emphasised the need to find a systemic solution to atherosclerosis, possibly through novel approaches to reducing the effects of inflammation. In a plenary session on presymptomatic detection of atherosclerosis, the importance of defining high-risk populations was emphasised (Sidney Smith, Chief Scientific Officer, American Heart Association, Dallas, USA), as the first manifestation of vascular disease is often a catastrophe — myocardial infarction, stroke or sudden cardiac death. Techniques reviewed included global risk factor algorithms such as those based on the Framingham study (Sidney Smith, Chief Scientific Officer, American Heart Association, Dallas, USA), the use of ultrasound to estimate arterial-wall thickness (Olli Raitakari, Senior Lecturer, University of Turku, Turku, Finland), the use of computed tomography scanning with and without contrast to detect coronary calcification and/or define coronary stenoses, and the use of magnetic resonance imaging to outline areas of myocardial damage and even plaque characteristics. Steven Nissen (Vice Chairman, Cardiovascular Division, Cleveland Clinic, Cleveland, USA) presented exciting new data on the reversibility of atherosclerosis with aggressive cholesterol lowering. New intravascular ultrasound studies have shown that coronary plaques can undergo regression and stabilisation, potentially translating into clinical benefit for people with coronary artery disease. InterventionA major focus of interventional cardiology was the exciting results of trials using drug-eluting stent technology. Substudies from the RAVEL trial2 and smaller pilot registries suggest that sirolimus, a macrolide antibiotic with powerful antiproliferative properties, effectively prevents restenosis de novo not only in coronary lesions and femoral artery lesions but also with in-stent restenosis. Patients with diabetes seem to benefit to the same extent as those without diabetes. Promising data were also reported for stents eluting paclitaxel, while ongoing clinical trials are evaluating other drugs. ArrhythmiasThe highlight of the sessions on arrhythmias was the presentation by Bernard Gersh (Professor of Medicine, Mayo Clinic, Rochester, USA) of data from the AFFIRM study, in which 4060 patients with recent paroxysmal or chronic atrial fibrillation were randomly allocated to either a "rate control" arm (with emphasis on obtaining an acceptable ventricular response rate) or a "rhythm control" arm (with antiarrhythmic drugs and elective cardioversion to attain and maintain sinus rhythm). The primary outcome measure of the study was total mortality: there were 306 deaths in the rate control group, compared with 356 deaths in the rhythm control group (P = 0.056). For other endpoints, such as hospitalisation, ischaemic stroke and arrhythmia attributable to antiarrhythmic drugs, the rate control group also tended to do better. Nearly all strokes occurred in patients who had an international normalised ratio of less than 2.0 or who were not taking warfarin, emphasising the importance of anticoagulation therapy regardless of the treatment strategy. The general conclusion of this landmark study is that decisions on returning patients to sinus rhythm with aggressive antiarrhythmic therapies can be based largely on symptoms and patient preferences rather than the (incorrect) assumption that this approach will improve prognosis. Heart failureHeart failure remains the leading cause of medical admission in people over 65 years, and its prevalence is increasing as the population ages. The high level of morbidity associated with heart failure was illustrated by Duc and colleagues,3 who found that major depression is present in 18% of patients who have heart failure, and depressive symptoms in another 26%. These conditions are often unrecognised and untreated. The emerging role of B-type natriuretic peptide (BNP) in heart failure management was highlighted in the sessions. Post and colleagues4 reported that measuring BNP can help to distinguish cardiac causes of dyspnoea from non-cardiac causes in the emergency department. Mean levels of BNP were 83 pg/mL in patients with non-cardiac-related dyspnoea and 905 pg/mL in patients with heart failure. Aronson et al5 showed that administration of BNP increased heart rate variability, a surrogate for improved prognosis (heart rate variability is an indicator of autonomic function, low variability being associated with dysfunction and adverse prognosis). Carvedilol can be successfully initiated and titrated, and withdrawal rates have been low, even in high-risk groups such as elderly people6 and those with severe heart failure.7 Krum et al (in the COPERNICUS study)7 showed that within the first eight weeks of therapy there was no excess of clinical events, and death in high-risk groups was less for carvedilol than placebo (3 v 15 deaths; P = 0.005). The efficacy of biventricular pacing to achieve ventricular resynchronisation also received attention: the MIRACLE study8 of patients with moderately severe heart failure and wide QRS interval (> 130 msec) showed improved functional status, quality of life and exercise tolerance after this treatment. While "high tech" approaches to heart failure were featured in some presentations, a Spanish study showed that patient education through home visits, telephone contact and clinic review could halve the number of readmissions for heart failure.9 Other studies of home-based education also reinforced this finding, with Stewart et al, in a four-year follow-up study,10 demonstrating benefits in terms of reduced mortality and cost savings from reduced readmission. Acute coronary syndromesLars Wallentin (Director of Cardiology, Uppsala University Hospital, Uppsala, Sweden) presented late results from the FRISC2 study, which had shown the benefit of early revascularisation (by either angioplasty or bypass surgery) in patients with unstable angina or a small infarction. Benefit was maintained at two years, with death or infarction reduced from 16.3% to 12.1%. He speculated that these results will lead to increased intervention for acute coronary syndromes, but noted that the cost–benefit ratio could be maximised by selecting patients at increased risk based on clinical predictors. Despite the recent development of more powerful thrombolytic drugs than tissue plasminogen activator (tPA), initial studies showed no clinical benefit and possibly increased haemorrhage. It appears the thrombolytic ceiling has been reached, and this is probably also true of combinations of tPA with antithrombotic drugs. The one-year results of the GUSTO V study of abciximab plus tPA treatment for patients with ST-elevation infarction showed no reduction in mortality. This was similar to the 30-day findings in the same study (Michael Lincoff, Associate Professor of Medicine, Cleveland Clinic Foundation, Cleveland, USA). Thus, the significant early reduction in recurrent infarction and rescue angioplasty with abciximab did not translate into reduced late mortality. The most promising strategies for ST-elevation infarction involve prehospital fibrinolysis and early direct angioplasty. The latter strategy was investigated in a national study in Denmark (DANAMI-II), whose one-year results were presented by Henning Andersen (Professor of Cardiology, Skejby University Hospital, Aarhus, Denmark). There was reduced death and reinfarction in patients having angioplasty compared with those treated with thrombolytic agents, even though many were transported long distances by ambulance to the hospital performing the angioplasty. Most of the benefit was in reduced reinfarction, a result that may also be achievable with lytic therapy plus low molecular weight heparin, together with elective revascularisation in the first few days after infarction. Molecular biology In a plenary session on gene and cell therapy, speakers highlighted the potential and possible limitations of a molecular biology approach for end-stage heart disease. Genes to promote angiogenesis have been used in early clinical trials of patients with severe coronary and peripheral vascular disease, with some promising results summarised by Elizabeth Nabel (Director, Clinical Research Program, National Heart, Lung, and Blood Institute, Bethesda, USA). The next phase was to use endothelial progenitor cells to assist in the cellular component of the response. Early data on the possible benefit of muscle stem-cell therapy for severe heart failure were presented by French11 and Dutch12 investigators. There was some concern that skeletal myoblasts may contribute to arrhythmogenesis. The winner of the International and CSANZ Young Investigator Basic Science Award, Thomas Yeoh (Research Fellow, Victor Chang Institute, Sydney), presented data on the control mechanisms of proliferation of skeletal muscle stem cells. This area of research is receiving intense interest internationally. In a provocative presentation entitled "Bench to bedside", Claude Lenfant (Director, National Heart, Lung, and Blood Institute, Bethesda, USA) stressed the need for translating the discoveries in the basic sciences into clinical care. In other sessions, Christine Seidman (Professor of Medicine and Genetics, Harvard Medical School, Boston, USA) showed how understanding gene defects and the changes they produce in myocardial proteins is unlocking the mechanism of an increasing number of cardiomyopathies underlying heart failure. Highlights of the 14th World Congress of Cardiology* Worldwide issues Epidemic of cardiovascular disease in developing countries Tobacco, diabetes and obesity Global cardiovascular risk assessment Atherosclerosis Inflammation Presymptomatic detection of coronary artery disease Reversibility with aggressive cholesterol reduction Intervention Drug-eluting stents Arrhythmia Rate or rhythm control for atrial fibrillation Heart failure B-type natriuretic peptide Beta-blockers Outpatient management Acute coronary syndromes Acute intervention New fibrinolytics and antithrombotics Molecular biology Gene and cell therapy Genes and cardiomyopathy * Some of the highlights are available as a webcast on <http://www.prous.com/wcc2002/program.asp#> (accessed 8 September 2002, no longer available).

Saul B Freedman PhD, FRACP

The benefits of statin therapy do not come without financial cost The aim of the recently reported Heart Protection Study1 in the United Kingdom, with over 20 000 participants aged 40–80 years, was to establish whether statin therapy is of benefit to people who are at high risk of cardiovascular disease (CVD) but have average-to-low levels of total cholesterol and LDL-cholesterol. High-risk patients (defined as those having previous coronary heart disease, diabetes, stroke, or peripheral vascular disease) were treated with simvastatin (40 mg daily), antioxidant vitamins (20 mg beta-carotene, 250 mg vitamin C and 600 mg vitamin E daily) or placebo in a 2 × 2 factorial design. Among patients allocated to the antioxidant arm of the trial, there was no change in incidence of any prespecified endpoints, and there were small but significant increases in blood levels of LDL-cholesterol and triglycerides, which have the potential to increase CVD risk with long-term antioxidant use.2 High-dose antioxidant therapy is therefore not recommended.3 Reductions in cardiovascular events (including myocardial infarction, stroke and either coronary or peripheral arterial revascularisation) occurred with simvastatin therapy in women, elderly people, and people with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes (see Box). Translating the results of the HPS into clinical practice, patients with an absolute overall CVD risk of more than 17% over five years (the lowest rate occurring in any subgroup of the HPS treated with placebo) should receive high-dose statin therapy, equivalent to 40 mg/day simvastatin, independent of baseline levels of total cholesterol; and other cardioprotective therapy, such as β-blockers and aspirin. Overall CVD risk can be estimated with the National Prescribing Service charts,4 which refer to CVD rather than coronary heart disease risk — a strategy flowing from the HPS outcomes.1,4 These charts, based on the Framingham study, provide only an approximation of absolute risk, but serve as a useful guide. Examples of patients with five-year CVD risk above 17% include most men over 60 years who smoke and have diabetes, and a 60-year-old non-smoking, non-diabetic man with blood pressure of 160/95 mmHg and a total cholesterol/HDL-cholesterol ratio of 6: 1.4 Benefits are likely to occur after 12 months of statin therapy, with greater benefits occurring the longer therapy is continued. Allowing for non-compliance, the HPS showed that about a third of major CVD events are likely to be prevented by statin therapy over five years. In the HPS, 23% of patients in the simvastatin group were smokers, 22% were being treated with antihypertensive agents, 20% with β-blockers, 25% with angiotensin-converting enzyme inhibitors (ACE inhibitors) and 21% with aspirin. Relative risk reductions in CVD incidence of up to 80% may be expected when statins are combined with standard cardioprotective agents (aspirin, β-blockers and ACE inhibitors) and stopping smoking.3 Given that CVD reduction in the HPS was independent of baseline cholesterol levels, it has been suggested that lipid levels need not be measured before commencing statin therapy in high-risk patients.3 However, fasting levels of triglycerides and HDL-cholesterol should be measured after 1–2 months, as therapy may need to be modified if these lipids are inadequately controlled by statin therapy alone. For example, gemfibrozil therapy may be considered for patients with low HDL-cholesterol levels.5 The HPS included about 6000 individuals with diabetes — the largest number in any statin trial reported to date. The CVD event rate for placebo-treated diabetics without coronary heart disease was 18.6%, compared with 22.5% for non-diabetics with coronary heart disease. Thus, the HPS confirms diabetes as a "coronary-equivalent" risk disorder for CVD.6 However, risk of CVD may vary from low to very high, depending on age and other risk factors, so it is still necessary to determine the global risk of CVD for an individual with diabetes when assessing the need to treat with a statin.4 Subjects at highest risk of CVD in the HPS had slightly elevated baseline serum creatinine levels (> 200 μmol/L), although only results of univariate analysis have been provided. The HPS confirms the high CVD risk in patients with impaired renal function and also supports the need for treatment of their dyslipidaemia.7 Caution is required in giving statin therapy to patients with more severe renal impairment, as they are at increased risk of myopathy.8 In the HPS, the safety profiles for statin and placebo therapy were similar. This finding may partly be a consequence of the exclusion of patients who showed adverse reactions to simvastatin during a 4–6-week run-in period leading up to the trial. However, only 32% of 63 603 screened patients were allocated to receive simvastatin in the study, so the low adverse event rate in the study may not necessarily apply to an unselected population. Of particular importance with regard to safety was the low incidence of myopathy (defined as serum creatine kinase levels exceeding 10 times the upper limit of normal), which occurred in only 11 simvastatin-treated patients and six placebo-treated patients. These results are reassuring, but muscle symptoms and creatine kinase levels should still be monitored periodically, and withdrawal of statin therapy should be considered if myalgia occurs or creatine kinase levels rise to more than three times the upper limit of normal.9 There were no apparent safety concerns in patients with low baseline LDL-cholesterol levels (< 3 mmol/L), in whom average LDL-cholesterol levels during the trial were 1.8 mmol/L in the simvastatin-treated group and 2.7 mmol/L in the group receiving placebo. The association between low levels of total cholesterol and increased cerebral haemorrhage found in a study by Iso et al10 was not borne out by the HPS. The safety and efficacy of treatment with 40 mg/day of simvastatin demonstrated by the HPS will probably result in a higher average dose being used in Australia, where the current average dose is 25 mg/day (Glen Godresse, Specialist/Hospital Product Manager, Merck Sharp and Dohme Australia Pty Ltd, personal communication). The benefits of statin therapy do not come without financial cost, although the long-term savings as a result of statin therapy are very likely to outweigh that cost.11 As CVD remains the single most important cause of mortality in Australia, consideration should be given to extending the availability of statins under the Pharmaceutical Benefits Scheme to include patients shown in the HPS to benefit from therapy: diabetics, women over 40 years, elderly people, and those with peripheral vascular disease, renal disease and low-to-average cholesterol levels, if their estimated global CVD risk exceeds 17% over five years.4 Absolute risk reductions and numbers needed to treat to prevent one cardiovascular event1 Event ARR (%)* NNT† All-cause mortality 1.8% 56 Mortality due to CHD 1.5% 83 Non-fatal myocardial infarction 2.1% 48 Coronary revascularisation 2.6% 38 Ischaemic stroke 1.2% 83 MVE without baseline CHD 4.7% 21 MVE with baseline CHD 5.7% 18 MVE with baseline creatinine > 200μmol/L 9.0% 11 MVE in patient aged < 65 years 5.2% 19 MVE in patient aged ≥ 70 years 5.1% 20 CHD = coronary heart disease. MVE = major vascular event (includes CHD, stroke, revascularisation). * Absolute risk reduction (%), simvastatin therapy v placebo. † Number needed to treat with simvastatin 40 mg/day to prevent one event over 5.3 years.

Ian Hamilton-Craig PhD FRACP

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels.Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo.Patients and setting: 9014 patients aged 35–75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992.Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life.Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%–4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626–$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%).Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Paul P Glasziou FRACGP, PhD · Simon D Eckermann BEc(Hons), BSc(Ma · Sarah E Mulray BA · R John Simes FRACP, MD · Andrew J Martin MA, PhD · Adrienne C Kirby BSc(Hons), MSc · Susan Caleo BPharm, GradDipSci · Jane P Hall BA, PhD · Harvey D White DSc, FRACP · Andrew M Tonkin MD, FRACP

Benefits depend on the patient’s absolute cardiovascular and bleeding risks The benefit of aspirin for patients with previous symptomatic atherothrombosis of the heart, brain and limb in the secondary prevention of recurrent serious vascular events is well established. However, the role of aspirin in the primary prevention of cardiovascular disease among people who have no symptoms of vascular disease is controversial.1 A recent summary of the evidence has prompted recommendations from the third US Preventive Services Task Force2,3 and the American Heart Association.4 The evidence is based on a systematic review of five randomised controlled clinical trials of the effectiveness and safety of long-term aspirin use (75–500 mg a day or every other day) over 3–7 years in over 50 000 individuals with no previous symptomatic cardiovascular disease.5-9 Most participants were middle-aged men, although there were more than 10 000 women included in two trials and substantial numbers of patients aged 70–80 years in four of the five trials. Among patients randomly allocated to receive aspirin, the rate of subsequent serious vascular events (non-fatal stroke, non-fatal myocardial infarction, or death due to vascular causes) was reduced significantly, from 4.8% (no aspirin) to 4.2% (aspirin) over about 56 months' follow-up. This is an odds reduction of 13% (95% CI, 5%–19%) and an annual risk reduction of about 0.1% (ie, one serious vascular event avoided per 1000 patients treated with aspirin for one year) (see Box). Most of the benefits of aspirin were due to a significant 28% (95% CI, 13%–40%) reduction in the odds of a coronary event (myocardial infarction or sudden death). There was no reduction in the occurrence of all stroke. However, aspirin was associated with a non-significant 40% (95% CI, −10% to 100%) increase in the odds of haemorrhagic stroke, which is consistent with the excess risk of haemorrhagic stroke seen in secondary prevention trials using aspirin.1 In absolute terms, this represents an excess risk of one haemorrhagic stroke per 10 000 patients treated with aspirin per year.10 Aspirin was also associated with a 70% (95% CI, 40%–110%) increase in the odds of major extracranial (mainly gastrointestinal) haemorrhage, which is an excess of 0.7 (95% CI, 0.4–0.9) major extracranial haemorrhages per 1000 patients treated with aspirin per year (see Box).10 The Preventive Services Task Force concluded that there is now good evidence that aspirin lowers the incidence of coronary heart disease (CHD) in adults who are at increased risk, and that it also increases the incidence of gastrointestinal bleeding.2 It considered that there was fair evidence that aspirin increases the risk of haemorrhagic stroke.2 The evidence was most reliable for men aged 40–75 years and less reliable for women and older men. The optimum dose of aspirin is not known, but dosages of 75–150 mg/day seem to be as effective as higher doses and are associated with a lower risk of adverse gastrointestinal effects. The American Heart Association recommends low-dose aspirin prophylaxis in people with a 10-year CHD risk of over 10% (ie, > 1% per year),4 whereas the Preventive Services Task Force recommends aspirin for people with a five-year CHD risk of over 3% (ie, > 0.6% per year).2,3 The latter is justifiable, in our view: for every 1000 patients with a 3% risk of a coronary event over five years, long-term aspirin therapy prevented 4–12 coronary events and caused 0–2 haemorrhagic strokes and 2–4 major gastrointestinal bleeding events. This represents a benefit-to-harm ratio of about 2.0 (see Box). The benefit-to-harm ratio of aspirin was most favourable among people at high risk of a future cardiovascular event and low risk of haemorrhagic complications. The implication for clinicians is that decisions to prescribe aspirin therapy for the primary prevention of cardiovascular events should be based on an assessment of the patient's absolute risk of a vascular event without aspirin, the absolute risk of a gastrointestinal or intracranial haemorrhage with aspirin, and the patient's preference. In addition, decisions about aspirin therapy should be reviewed at least every five years, or when new vascular risk factors are detected. Risk stratification should incorporate specific information about multiple risk factors, rather than simply counting the number of risk factors.11,12 Risk factors for cardiovascular disease include increasing age, being male, cigarette smoking, increasing blood pressure, increasing blood total cholesterol level, decreasing high-density lipoprotein cholesterol level, raised fasting blood glucose level (ie, diabetes mellitus), and a positive family history of cardiovascular disease (in younger adults).4,13 Risk factors for haemorrhagic complications of aspirin include increasing age, any bleeding diathesis, uncontrolled hypertension, and concomitant use of other nonsteroidal anti-inflammatory agents or anticoagulants. Enteric-coated or buffered preparations of aspirin do not clearly reduce adverse gastrointestinal effects. People at increased cardiovascular risk who may wish to consider long-term aspirin therapy (75–150 mg/day) are men over 40 years of age, postmenopausal women, and younger people with risk factors for cardiovascular disease (eg, hypertension, diabetes).4,13 However, there is still insufficient information to reliably identify the minority of individuals who will benefit and the minority who will be harmed by regular treatment with aspirin. Further information will soon be available from several studies: the Women's Health Study (comparing aspirin 100 mg taken every alternate day with placebo among 40 000 healthy postmenopausal women); the Aspirin in Asymptomatic Atherosclerosis trial (comparing low-dose aspirin with placebo in 3300 middle-aged participants with asymptomatic peripheral atherosclerosis, identified by an ankle brachial pressure index of ≤ 0.9); and the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance) trial (comparing aspirin with a clopidogrel/aspirin combination for preventing serious vascular events among about 15 000 people at high risk of cardiovascular disease who are currently taking aspirin). In the meantime, the challenge for clinicians is to translate the evidence into practice by ascertaining the absolute risk of subsequent serious vascular events for all people who may be at risk, and to prescribe long-term aspirin 75–150 mg/day, with long-term follow-up, for those with an absolute risk of CHD exceeding 3% over the next five years. The challenge for academic clinicians is to devise more valid "risk calculators" that incorporate the risk of serious cardiovascular events and the risk of adverse events, such as intracranial and gastrointestinal haemorrhage. Summary (based on five randomised controlled trials) of the effectiveness of long-term aspirin use in primary prevention of coronary events3 Absolute risk (%) Number of events avoided or caused (95% CI)* Outcomes Control Aspirin Odds ratio (95% CI) AR 1% AR 3% AR 5% Benefits (events avoided) All coronary events (non-fatal or fatal MI, or sudden death) 2.4% 1.9% 0.72 (0.60–0.87) 3 (1–4) 8 (4–12) 14 (6–20) Fatal coronary events 0.7% 0.6% 0.87 (0.70–1.09) All-cause mortality 3.5% 3.4% 0.93 (0.84–1.02) 1 (0–2) 2 (0–5) 4 (0–8) Non-fatal stroke, non-fatal MI, or death due to vascular causes 4.8% 4.2% 0.87 (0.81–0.95) 1 (0–2) 4 (2–6) 6 (2–10) No change All stroke 1.3% 1.4% 1.02 (0.85–1.23) NC NC NC Harms (events caused) Haemorrhagic stroke† 0.17% 0.22% 1.4 (0.9–2.0) 1 (0–2) 1 (0–2) 1 (0–2) Major gastrointestinal bleeding event‡ 0.5% 0.8% 1.7 (1.4–2.1) 3 (2–4) 3 (2–4) 3 (2–4) Benefit-to-harm ratio 0.75 2.0 3.5 MI = myocardial infarction. NC = no change. * Events per 1000 patients treated for five years with aspirin, compared with no aspirin, according to the patient's baseline absolute risk (AR) of coronary heart disease over the next five years. † Data from secondary prevention trials suggest that increases in haemorrhagic stroke may be offset by reduction in ischaemic stroke in patients at very high risk for cardiovascular disease (ie, > 10% risk over five years). ‡ Rates may be two to three times higher in people aged over 70 years.

Graeme J Hankey MD FRCP FRACP · John W Eikelboom MSc FRACP FRCPA

In reply: Aroney's letter raises a number of important issues. The first of these is the question of whether a scientific fact requires the blessing of peer review to become established as such. The corollary of this is whether or not all peer-reviewed facts are necessarily true. The answer to both questions is probably no. The second issue is how to control a media report, irrespective of whether it is based on a peer-reviewed study. The issue which concerns Aroney is an abstract presentation of the association of gastrointestinal bleeding with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase II (COX-II) inhibitors, the conclusion of which was that, while the last two might be important in their own right, concurrent use of aspirin, even in a small dose, was more closely associated with bleeding risk, particularly if there was a past history of peptic ulceration.1 A "meta-analysis" of the media reports, which included both television and radio in addition to the quoted report in the Sydney Morning Herald,2 would have made it clear that the theme of the interviews reaffirmed the relative safety of aspirin in the vast majority of individuals, and highlighted the risk of aspirin use concurrently with NSAIDs and COX-II inhibitors, particularly when there is a history of past ulceration. The fact that the SMH report focused on one aspect of the study was counterbalanced by the others. We do not know how journalistic reporting is controlled. A primary question is whether or not aspirin is an effective agent for the prevention of cardiovascular disease beyond the management of acute myocardial infarction. More recent literature than that quoted by Aroney is now questioning the overall cardioprotective value of aspirin.3 This showed that aspirin given as prophylaxis against cardiovascular disease increased the risk of sudden death in every secondary prevention study and left the overall rate of myocardial infarction unchanged.4 Aspirin consistently failed to reduce overall mortality in every study of long-term prophylaxis after myocardial infarction, and in all but one after stroke.3 Furthermore, Cleland and colleagues have argued that a series of meta-analyses, which most people have accepted as proof of the efficacy of aspirin, are of doubtful validity.4 They questioned whether it is appropriate for the medical community to invest so much time and effort in prescribing aspirin and dealing with the adverse consequences of its long-term ingestion to the neglect of other, better proven and apparently more effective therapies such as angiotensin-converting enzyme inhibitors, β-blockers, and statins. At the very least, it can be said that there is controversy in the cardiovascular literature about the benefits of aspirin. Just as important is the issue of the safety of long-term aspirin use for cardioprotection. A recent multidisciplinary expert statement on NSAIDs concluded that, on current evidence, prophylactic use of aspirin should be reserved for patients with established vascular disease, because in other patients bleeding risks may outweigh cardiovascular benefit.5 A Danish study showed that 100–150 mg of aspirin daily increased the risk of haematemesis by a factor of 2.6, with no difference in the risk between enteric and non-coated product; when combined with an NSAID the risk was increased by a factor of 5.6.6 The authors concluded that the bleeding risk may offset some of the benefits of aspirin. It is no longer appropriate to simply "bury" the adverse gastrointestinal effects of low-dose aspirin in the NSAID side-effect "basket".7 It is apparent to us that dogma should not be so enshrined that it prevents the discussion of issues that might helpfully modify that dogma.

Terry D Bolin · James V Bertouch MD

In reply: The letter from Aroney displays some basic misunderstandings of the role of the media in reporting medical issues. Aroney states that "the press [has] a responsibility . . . to avoid recommendations which are not evidence-based and which detract from our efforts to reduce mortality from . . . cardiovascular disease." A press article does not itself make recommendations when it reports the recommendations of others — an essential distinction. In addition, the press has no responsibility to follow the agenda of the medical profession and its slavish insistence on the dogma of evidence-based medicine. The press owes doctors no more favours than it owes any other sector of the community. The role of the press is to raise and debate issues of public interest in a manner that is balanced and responsible. The news report about aspirin did all of this.1 We agree that publication in a peer-reviewed journal may add scientific credibility to research findings and that this may sometimes make them more newsworthy. But our responsibility is to report medical matters of interest to the community, which means we are not limited to peer-reviewed findings. Any substantial fact, observation or opinion relating to medical practice is fair game for a newspaper's attention. After the findings of Bertouch and colleagues were presented at a conference,2 they entered the public domain, as did their later comments made to us directly. It was entirely proper to report them. The fact that the gastrointestinal bleeding study was conducted by two heads of department at a major Sydney teaching hospital was instrumental to our decision to position and headline the report prominently. These individuals are respected experts in their fields, and they expressed to us serious concern about the degree to which aspirin was implicated in gut haemorrhage. It was that concern which led us to focus on the aspirin findings within the broader study. The news process is always selective and there is no obligation to give equal emphasis to all findings. The magnitude of follow-up by other media confirms the inherent public interest in the topic. It has previously been suggested that medical journalists are behaving irresponsibly when they step outside the strictures of peer review.3,4 Yet it is a basic tenet of journalistic ethics that journalists should be independent.5 Why, then, would we subscribe to the doctrine of evidence-based medicine, with all its flaws? We, and the community, have every right to be sceptical of the tyranny of peer review when the pharmaceutical industry manifestly uses financial muscle to influence what is studied and what is published.6 Even the Medical Journal of Australia accepts anecdotal findings when it can persuade itself the public interest is involved, recently publishing an eyewitness account of conditions inside an immigration detention centre7 and defending this on the basis that "our readership is sophisticated enough to interpret the content of such articles."8 Sydney Morning Herald readers are also sophisticated. On what basis should they have been denied this pertinent information about a widely used medicine — that doctor still knows best?

Julie Robotham BA(Oxon) · Robert Whitehead

Objectives: To determine (i) factors which predict whether patients hospitalised with acute myocardial infarction (AMI) receive care discordant with recommendations of clinical practice guidelines; and (ii) whether such discordant care results in worse outcomes compared with receiving guideline-concordant care.Design: Retrospective cohort study.Setting: Two community general hospitals.Participants: 607 consecutive patients admitted with AMI between July 1997 and December 2000.Main outcome measures: Clinical predictors of discordant care; crude and risk-adjusted rates of inhospital mortality and reinfarction, and mean length of hospital stay.Results: At least one treatment recommendation for AMI was applicable for 602 of the 607 patients. Of these patients, 411(68%) received concordant care, and 191 (32%) discordant care. Positive predictors at presentation of discordant care were age > 65 years (odds ratio [OR], 2.5; 95% CI, 1.7–3.6), silent infarction (OR, 2.7; 95% CI, 1.6–4.6), anterior infarction (OR, 2.5; 95% CI, 1.7–3.8), a history of heart failure (OR, 6.3; 95% CI, 3.7–10.7), chronic atrial fibrillation (OR, 3.2; 95% CI, 1.5–6.4); and heart rate ≥ 100 beats/min (OR, 2.1; 95% CI, 1.4–3.1). Death occurred in 12.0% (23/191) of discordant-care patients versus 4.6% (19/411) of concordant-care patients (adjusted OR, 2.42; 95% CI, 1.22–4.82). Mortality was inversely related to the level of guideline concordance (P = 0.03). Reinfarction rates also tended to be higher in the discordant-care group (4.2% v 1.7%; adjusted OR, 2.5; 95% CI, 0.90–7.1).Conclusions: Certain clinical features at presentation predict a higher likelihood of guideline-discordant care in patients presenting with AMI. Such care appears to increase the risk of inhospital death.

Ian A Scott FRACP, MHA · Catherine M Harper BSc, MPHTM