LAUSR

ABSTRACT Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease (CMD) and/or coronary artery vasospasm (CAVS) being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around two disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators such as nitrates have been first-line anti-anginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in terms of symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an anti-anginal first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation via nitric oxide. Additionally, NCO has ATP-dependent potassium channel-agonist activity (KATP), mediating microvascular dilatation. Hence, it has proven effective in both CAVS and CMD, typically challenging patient populations. Moreover, emerging evidence suggests cardiomyocyte protection against ischemia via ischemic preconditioning (IPC) may be mediated via KATP-agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease (CAD), following myocardial infarction, and perhaps even among patients with congestive heart failure (CHF). This review aims to summarize the mechanism of action of NCO, its efficacy as an anti-anginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging non-cardiac indications for NCO use.Keywords: angina, stable ischemic heart disease, anti-anginal, efficacy, cardioprotective.