SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

The term acute coronary syndrome refers to a range of acute myocardial ischaemic states. It encompasses unstable angina, non-ST segment elevation myocardial infarction (ST segment elevation generally absent), and ST segment elevation infarction (persistent ST segment elevation usually present). This article will focus on the role of percutaneous coronary intervention in the management of unstable angina and non-ST segment elevation myocardial infarction; the next article will address the role of percutaneous intervention in ST segment elevation infarction.Although there is no universally accepted definition of unstable angina, it has been described as a clinical syndrome between stable angina and acute myocardial infarction. This broad definition encompasses many patients presenting with varying histories and reflects the complex pathophysiological mechanisms operating at different times and with different outcomes. Three main presentations have been describedangina at rest, new onset angina, and increasing angina. PathogenesisThe process central to the initiation of an acute coronary syndrome is disruption of an atheromatous plaque. Fissuring or rupture of these plaques-and consequent exposure of core constituents such as lipid, smooth muscle, and foam cells-leads to the local generation of thrombin and deposition of fibrin. This in turn promotes platelet aggregation and adhesion and the formation of intracoronary thrombus.Unstable angina and non-ST segment elevation myocardial infarction are generally associated with white, platelet-rich, and only partially occlusive thrombus. Microthrombi can detach and embolise downstream, causing myocardial ischaemia and infarction. In contrast, ST segment elevation (or Q wave) myocardial infarction has red, fibrin-rich, and more stable occlusive thrombus.

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Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD. This places further emphasis on efforts at smoking cessation to improve revascularization benefits. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).