Acute coronary syndromes: consensus recommendations for translating knowledge into action

To the Editor: I thank Brieger and colleagues and Thompson for their comments on my article.1

Brieger et al2 refer to the United Kingdom National Institute for Health and Clinical Excellence Guideline Development Group that analysed the non-ST-elevation myocardial infarction (NSTEMI) trials to show an inverse relationship between rates of intervention and clinical outcomes.3 This is a post-hoc analysis and is therefore hypothesis generating rather than proof of concept; further, its results are confounded by the fact that intervention rates have increased in recent years, while medical treatment — particularly with clopidogrel and statins — has also improved.

Brieger et al then contend that the Variations in the Application of Cardiac Care in Australia study4 provides justification for an interventional approach. This study demonstrated that patients treated in hospitals without percutaneous coronary intervention (PCI) facilities fare worse than patients at hospitals with PCI. The likely reason for this is that these patients are less likely to receive cardiac rehabilitation, aspirin, statins, β-blockers and timely thrombolysis.

With respect to ST-elevation myocardial infarction (STEMI), Brieger and colleagues suggest that the evidence is even stronger because of CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction).5 In this study, patients treated medically were administered half-dose reteplase and full-dose abciximab. This treatment is not currently recommended and the study therefore has no relevance to the current debate.

Brieger et al state that I erroneously cited TRANSFER-AMI (Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction)6 as evidence against a strategy of routine urgent transfer. This is the largest contemporary trial that compares urgent transfer with routine selective transfer after thrombolysis in hospitals without PCI facilities. The trial is thus the most relevant to our discussion. The fact that clinicians chose to transfer 89% of patients for PCI after a mean time of 23 hours in the selective management group does not negate the lack of significant benefits of routine urgent transfer after thrombolysis. I agree that TRANSFER-AMI is limited by the high rate of intervention. The problem remains, however, that the guidelines mandate transfer of all STEMI patients and fail to provide evidence to justify it.

In the first paragraph of his editorial, Thompson7 cites the American College of Cardiology/American Heart Association guidelines8 as evidence for early coronary intervention. However, these guidelines state that “in initially stabilized UA [unstable angina]/NSTEMI patients, an initial conservative (selective invasive) strategy may be considered as a treatment option”.8 This statement is not in the Australian guidelines.

Thompson acknowledges that the ICTUS (Invasive versus Conservative Treatment in Unstable Coronary Syndromes) trial9 provides up-to-date medical treatment, but notes the lower mortality rates compared with patients in the ACACIA (Acute Coronary Syndrome Prospective Audit) registry.10 He therefore concludes that these patients were not high risk. Yet one of the entry criteria for the ICTUS trial was an elevated troponin level, which is defined as high risk in the Australian guidelines. I drew attention to the fact that the Australian guidelines seem to be over-inclusive in their definition of high risk.

The lower mortality rate in the ICTUS study and in other routine-versus-selective-PCI trials in NSTEMI presumably reflects exclusion of patients who are older, have other comorbidities such as renal impairment, or whose conditions are clinically unstable. Physicians treating patients such as those entered in the ICTUS trial — with electrocardiogram changes and a raised troponin level without other comorbidities or shock — should have the option to manage these patients with a selective invasive approach.

Thompson states “the conclusion that conservative management alone will remove the need to open a blocked artery is hardly justified based on the ICTUS study results, which comprise just over 10% of the evidence base”. I had included two meta-analyses of all of trials of routine intervention as the cornerstone of my argument and pointed out that they had not shown a reduction in mortality. The ICTUS trial confirmed the conclusions drawn from those trials and is the only trial in which medical treatment was adequate.

Thompson stated that I suggested that modern medical management could render invasive treatment irrelevant. This statement was not in my article.

In summary, nothing in the rebuttal by Brieger et al or Thompson’s editorial provided any real evidence to justify an expensive, invasive policy requiring routine urgent (as opposed to selective) transfer of all patients with ST-elevation acute coronary syndromes or NSTEMI for PCI, nor for the establishment of more PCI units throughout regional Australia.