LAUSR

The current era of management for coronary artery disease and acute coronary syndromes (ACS) is guided by high-level evidence from large-scale, prospective clinical trials. Although certain therapies such as early invasive therapy, dual antiplatelet therapy, and angiotensin-converting enzyme inhibition have clear prognostic benefits, use of sublingual glyceryl trinitrate therapy (GTN) after discharge appears to be guided by historic studies. The first reported use of GTN for the treatment of angina pectoris was in 1867. Despite the limited data, use of sublingual GTN after ACS is strongly embedded within guidelines, with 2 to 3 million patients per year from the United States and Europe alone being discharged after ACS with their bottle of spray or sublingual tablets to be used as required. This article aims to relook at this global “habit” in the setting of routine revascularization for ACS. The most accepted mechanism of GTN action is vasodilatation mediated by activation of soluble guanylate cyclase and production of cyclic guanosine monophosphate in vascular smooth muscle. In the setting of ACS, GTN-induced vasodilation of epicardial vessels and resistance vessels as well as collateral vessels may acutely improve myocardial perfusion until revascularization can be achieved. The current European Society of Cardiology guidelines, released in 2020, give a class I recommendation for the use of nitrates (sublingual or intravenous) for the treatment of ACS without persistent ST elevation in the setting of ischemic symptoms without contraindications.1 Similarly, the American Heart Association/American College of Cardiology guidelines provide a class I recommendation for the use of nitrates for management of both acute non–ST-segment– elevation myocardial infarction and ST-segment–elevation myocardial infarction in patients with “ongoing ischemic pain, except in the setting of treatment with phosphodiesterase inhibitors (PDE).”2 In all cases, recommendations are based on level C evidence and indicated for patients with ongoing ischemia before percutaneous intervention, with the authors stating that “the rationale for nitrate use in NSTE [non-ST elevation]-ACS is extrapolated from pathophysiological principles and clinical observations, experimental studies, and clinical experience.”2 The studies cited in the ACS guidelines have largely been conducted in the pre-percutaneous coronary intervention era and have evaluated long-acting nitrate formulations. These studies include the ISIS-4 study3 and the GISSI-3 trial.4 In the ISIS-4 study, 1 month of oral controlled-release mononitrate was compared with placebo. In this study, there was no significant difference in mortality between the 2 groups, no reduction in postinfarction angina, and no reduction in reinfarction rates. There was a significantly higher incidence of hypotension and headaches in the nitrate therapy arm.3 The GISSI-3 trial was a multicenter randomized clinical trial designed to assess the efficacy of lisinopril, transdermal GTN, and their combination in improving survival and ventricular function after acute myocardial infarction. This trial showed that compared with control, the systematic administration of transdermal GTN did not show any independent effect on the survival or ventricular function. There was also no significant effect on the incidence of reinfarction, but a small reduction in rates of postinfarction angina (20.0% versus 21.2%; P=0.033).4