Timing of Intervention in Non-ST Elevation Acute Coronary Syndromes

What Is the VERDICT?Article, see p 2741 U nlike in patients with ST segment elevation myocardial infarction, where the culprit coronary artery is occluded, leading to transmural ischemia, patients presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) usually have a patent culprit vessel with subendocardial ischemia.NSTE-ACS and ST segment elevation myocardial infarction are a continuum, and NSTE-ACS can progress to ST segment elevation myocardial infarction or complete vessel occlusion if left untreated.It is well established that an invasive approach compared with a conservative approach is beneficial in patients with NSTE-ACS. 1 What is less certain is whether early/urgent coronary angiography and intervention are beneficial in NSTE-ACS.The topic of timing of angiography in NSTE-ACS has been previously studied in randomized trials.[2][3][4][5][6][7][8] The largest, the TIMACS trial (Timing of Intervention in Acute Coronary Syndromes) (N=3031), compared early angiography and intervention in ≤24 hours versus delayed angiography >36 hours and found no difference in the primary outcome of death, myocardial infarction (MI), or stroke at 6 months (hazard ratio [HR], 0.85; 95% CI, 0.68-1.06).3 However, there was a 28% reduction in the secondary outcome of death, MI, or refractory ischemia (HR, 0.72; 95% CI, 0.58-0.89).Furthermore, there was a sizeable benefit for the primary outcome with early angiography and intervention in those patients at highest risk (GRACE risk score >140; HR, 0.65; 95% CI, 0.48-0.89;P=0.005; P for interac-tion=0.0097).In this issue of Circulation, Kofoed and colleagues 9 performed a randomized trial (N=2147) in patients with NSTE-ACS comparing early angiography (in ≤ 12 hours) to standard of care (angiography 48-72 hours) with a primary outcome of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.The median time of angiography was 4.3 hours in the early group and 61.6 hours in the standard-of-care group.Percutaneous coronary intervention was performed in ≈50% of patients and coronary bypass surgery in 12%.About a third of patients had no significant coronary stenosis.There was no difference in primary outcome (HR, 0.92; 95% CI, 0.78-1.08)at a median of 4.3 years.There was a significant reduction in nonfatal MI (HR, 0.73; 95% CI, 0.56-0.96)over follow-up that was not evident early (in ≤15 days).There were no reductions individually in the outcomes of death, refractory angina, or heart failure.In the high-risk subgroup (GRACE risk score >140), there was a benefit of early angiography for the primary outcome (HR, 0.81; 95% CI, 0.67-1.00).These findings are consistent with the TIMACS trial, particularly the benefit in the high-risk subgroup (Figure ). 3 There is a clear biological rationale that those at high-

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