Acute coronary syndromes: consensus recommendations for translating knowledge into action
Authors: David B Brieger, Derek Chew, Constantine Aroney, Phil Aylward, Darren Walters, Anne-Maree Kelly and Andrew Boyden
Published online: 1 November 2010
In reply: We thank Forge for his continued and welcome contribution to this debate.
He is critical of our reference to the National Institute for Health and Clinical Excellence (NICE) guidelines, which show an inverse relationship between rates of intervention and clinical outcomes. The NICE analysis is supported by others,1 and we stand by our argument that if studies with greater differences in the randomisation arms show a greater treatment effect, the strength of the evidence supporting the intervention is enhanced. Dismissing this type of analysis on scientific grounds is disingenuous and contrary to National Health and Medical Research Council recommendations regarding the assessment and application of scientific evidence.2
Data supporting the role of invasive therapy in management of acute coronary syndromes (ACS) continue to evolve. A recently published patient-level meta-analysis of three studies, comprising 5-year outcomes of 5467 patients, showed a significant reduction in myocardial infarction (hazard ratio [HR], 0.77; 95% CI, 0.65–0.90), with consistent trends towards reduction in cardiovascular death (HR, 0.83; 95% CI, 0.68–1.01) and all death (HR, 0.90; 95% CI, 0.77–1.05).3
This meta-analysis showed the largest absolute benefit among the highest-risk patients assessed by a global risk score, supporting evidence that risk stratification should involve more comprehensive clinical evaluation than that provided by a single biomarker.4
It is true that these studies have not shown a reduction in mortality. This is most likely to be an issue of power. Based on the number of patients studied in randomised trials so far, the power needed to detect a 10% difference in mortality between treatment strategies is only 27%.1
Regarding TRANSFER-AMI (Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction), Forge now agrees that there are limitations associated with the high transfer rates in the conservative arm, which are greater than those seen in contemporary Australian practice. When the conservative arm receives better-than-standard practice, the direct effect is a bias of the outcome towards the null, limiting the quantification of absolute benefit associated with routine urgent transfer. Forge dismisses CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) because of the management strategy in the conservative arm. The main limitation of this study is its small size; in an earlier study of 16 588 patients, combination half-dose reteplase and full-dose abciximab treatment had comparable mortality to full-dose reteplase alone.5
Finally, we would like to re-emphasise that National Heart Foundation of Australia (NHFA)/Cardiac Society of Australia and New Zealand (CSANZ) ACS guidelines are not prescriptive. They are designed to provide guidance to individual clinical practice, not to mandate one form of practice. Adherence to guidelines has been demonstrated to improve outcomes when instituted as part of a coordinated quality improvement strategy across a health care system. In addition to provision of optimal medical therapy and risk factor modification, approaches to ACS that incorporate timely access to revascularisation have made a significant contribution to this improvement in outcomes.
Competing interests
References
- Hoenig MR, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev 2010; (3): CD004815. 0_CBBIEECD
- O’Connell D, Glasziou P, Hill S. How to use the evidence: assessment and application of scientific evidence. Canberra: National Health and Medical Research Council, 2000. 0_CBBIIAEC
- Fox KA, Clayton TC, Damman P, et al; FIR Collaboration. Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome: a meta-analysis of individual patient data. J Am Coll Cardiol 2010; 55: 2435-2445. 0_CBBHBAEE
- Steg PG, FitzGerald G, Fox KA. Risk stratification in non-ST-segment elevation acute coronary syndromes: troponin alone is not enough. Am J Med 2009; 122: 107-108. 0_i1095428
- Topol EJ; GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001; 357: 1905-1914. 0_CBBDAGBG
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