Great expectations

Abstract

We congratulate Alexander Jobs and colleagues1Jobs A Mehta SR Montalescot G et al.Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.Lancet. 2017; 390: 737-746Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar (Aug 19, 2017, p 737) for their meta-analysis of trials addressing the optimal timing of an invasive strategy in acute coronary syndromes (ACS), using individual or standardised tabulated data. Their analysis did not support a mortality benefit of an early strategy compared with a delayed strategy. In high-risk subgroups, although a benefit was observed with an early strategy, the risk–treatment interaction was not significant.1Jobs A Mehta SR Montalescot G et al.Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trials.Lancet. 2017; 390: 737-746Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar Mortality is unlikely to be an appropriate endpoint for such a trial. In fact, death is rare in patients with non-ST-elevation ACS who are admitted to the intensive care unit, with the exception of very high-risk patients, who are excluded from such trials. As in other studies related to ACS, a more relevant endpoint would be a composite of cardiovascular death, myocardial infarction, and urgent revascularisation.2Hicks KA Tcheng JE Bozkurt B et al.2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American College of Cardiology/American Heart Association Task Force on clinical data standards (Writing Committee to Develop Cardiovascular Endpoints data standards).J Am Coll Cardiol. 2015; 66: 403-469Crossref PubMed Scopus (351) Google Scholar Myocardial infarction and emergent revascularisation for recurrent ischaemia are the most likely consequences of a delayed strategy. Additionally, a delayed strategy has a large effect on patients and the health-care system by increasing infarct size and requiring emergent intervention. Furthermore, the trials included in the meta-analysis were done during a period in which the definition of ACS and its management have greatly varied. Pretreatment with P2Y12-ADP antagonists is no longer recommended in this clinical setting.3Bellemain-Appaix A Kerneis M O'Connor SA et al.Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis.BMJ. 2014; 349: 62-69Google Scholar, 4Montalescot G Bolognese L Dudek D et al.Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.N Engl J Med. 2013; 369: 999-1010Crossref PubMed Scopus (452) Google Scholar This recommendation is likely to affect the optimal treatment strategy for non-ST-elevation ACS, as the main hypothesis supporting delayed intervention was medical stabilisation of the atherothrombotic process. These points underline the need for additional trials with optimal selection criteria, up-to-date management—including absence of P2Y12-ADP antagonist pretreatment—and a more relevant endpoint (as seen in NCT02750579). We declare no competing interests. Optimal timing of an invasive strategy in patients with non-ST-elevation acute coronary syndrome: a meta-analysis of randomised trialsAn early invasive strategy does not reduce mortality compared with a delayed invasive strategy in all patients with NSTE-ACS. However, an early invasive strategy might reduce mortality in high-risk patients. Full-Text PDF Great expectations – Authors’ replyNon-ST-segment elevation myocardial infarction (NSTEMI) is associated with relevant mid-term mortality and might be associated with poorer long-term prognosis compared with ST-segment elevation myocardial infarction.1 All-cause mortality is the most objective and clinically meaningful endpoint regarding data quality of randomised controlled trials and patient prognosis. However, as pointed out by Gilles Lemesle and colleagues, all-cause mortality is unlikely to be an appropriate endpoint to power a randomised controlled trial funded by a government agency and investigating the optimal timing of invasive coronary angiography or other treatment strategies in non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Full-Text PDF