Will This Trial Change My Practice?

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Abstract

At EuroPCR, 2014, Paris, a new session format was introduced to analyse how results of clinical trial results impact on clinical practice. While cardiologists receive a large amount of scientific information from clinical studies, only a small part of it will impact on the decision-making process for individual patients. The aims of these sessions was therefore to achieve a detailed understanding of a particular published trial, to evaluate the relevance of new results for daily practice and to share current and future practice

Received date
26 August 2014
Accepted date
26 September 2014
Citation
RadcliffeCardiology.com, August 2014

Pages

Introduction
At EuroPCR, 2014, Paris, a new session format was introduced to analyse how results of clinical trial results impact on clinical practice. While cardiologists receive a large amount of scientific information from clinical studies, only a small part of it will impact on the decision-making process for individual patients. The aims of these sessions was therefore to achieve a detailed understanding of a particular published trial, to evaluate the relevance of new results for daily practice and to share current and future practice.

The ACCOAST Study
Before discussing the study, the chairperson, Professor Thomas Cuisset, asked the audience who had changed their daily practice in non-ST elevation myocardial infarction (NSTEMI) management since publication of the a Comparison of prasugrel at PCI or time of diagnosis of Non-ST elevation myocardial infarction (ACCOAST) study data. A substantial minority raised their hands.

What was Known Before this Trial?
Dr Rod Stables of the Liverpool Heart and Chest Hospital, United Kingdom presented a summary of current knowledge. Oral antiplatelet therapy is a core concept in cardiology. The clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) Trial found that in the first 24 hours, the relative risk reduction is 34 % and suggested that all patients presenting with acute coronary syndrome (ACS) should receive clopidogrel on admission.1 Furthermore, the Intracoronary stenting with antithrombotic regimen cooling off (ISAR-COOL) study in high-risk ACS patients showed that delaying intervention for prolonged antithrombotic treatment is not beneficial.2 A recent study found that upstream clopidogrel treatment prior to catheterisation laboratory arrival is associated with a significant decrease in the prevalence and extent of microvascular obstruction.3 Another study found that a loading dose of prasugrel 60 mg results in more rapid, potent, and consistent inhibition of platelet function than clopidogrel 300 mg.4 In summary, current evidence supports the use of oral antiplatelet therapy prior to coronary intervention in patients with ACS.

Trial Review – the Data, Statistics and Conclusions
Professor Peter Jüni of the University of Bern, Switzerland, described the ACCOAST trial. Patients (n=4022) with non-ST elevation ACS and a positive troponin level who were scheduled to undergo coronary angiography within 2–48 hours after randomisation, were randomly assigned to receive prasugrel (a 30 mg loading dose) before the angiography (pretreatment group) or placebo (control group).5 When percutaneous coronary intervention (PCI) was indicated, additional prasugrel (30 mg) was given in the pretreatment group at the time of PCI and prasugrel (60 mg) was given in the control group. The primary composite endpoint was death from cardiovascular causes, myocardial infarction (MI), stroke, urgent revascularisation and the need for glycoprotein IIb/IIIa bailout within the first seven days after randomisation. Safety endpoints were: thrombolysis in myocardial infarction (TIMI) bleeds and additional Safety and efficacy of enoxaparin in PCI Patients, an international randomised evaluation (STEEPLE) and Global use of strategies to open occluded arteries (GUSTO) bleeding criteria. Patient profiles and treatment timelines were representative of those seen in daily practice.

At 30 days, the rate of the primary efficacy end point did not differ significantly between the two groups (hazard ratio [HR] with pretreatment, 1.02) The result was therefore clear-cut: no evidence of benefit. The rate of the key safety end point of all TIMI major bleeding episodes through day seven was increased with pretreatment (HR, 1.90 p=0.006). Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69 % of the patients) but increased the rate of thrombolysis in myocardial infarction (TIMI) major bleeding at seven days. The study concluded that, in non-ST-elevation (NSTE) ACS patients managed invasively within 48 h of admission, pre-treatment with prasugrel does not reduce major ischaemic events within 30 days but increases major bleeding complications. Therefore a reappraisal of routine pre-treatment strategies in HSTE-ACS is needed.

ACCOAST – Take-home Message
Following the discussion of ACCOAST, most of the audience would still pretreat their patients. ACCOAST is an interesting clinical trial that asks a clinically relevant question, but is based on only drug. It is not known whether we can extrapolate these results to pre-treatment with established drugs that have been shown to be beneficial in other trials. The fact that an excess of bleeding complications were seen could be explained by the fact that many patients are not good candidates for prasugrel. A trial with ticagrelor would be interesting. An important message of ACCOAST is that getting patients into the catheterisation laboratory as soon as possible avoids many problems. However, many don’t have that opportunity. In these cases, the use of clopidogrel avoids coronary events. In conclusion, the trial is relevant but further study is required to determine whether we can advance current treatment for patients with ACS.

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References
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