Beneficial effects of nicorandil on exercise capacity in heart failure with preserved ejection fraction patients with concomitant coronary microvascular dysfunction

Prior studies have suggested a beneficial effect of nicorandil on coronary microcirculation. The present study investigated whether nicorandil improved exercise endurance as well as clinical outcomes in heart failure with preserved ejection fraction (HFpEF) patients with concomitant coronary microvascular dysfunction (CMD). In this randomized and controlled trial, 113 HFpEF patients with concomitant CMD were enrolled and allocated in a 1:1 ratio to receive either nicorandil or serve as controls for 24 months. Enrollment criteria included the absence of significant epicardial coronary artery stenosis and the presence of CMD, defined as a coronary flow reserve (CFR) of < 2.0 as assessed by myocardial contrast echocardiograpgy (MCE). The primary outcome was the change in exercise endurance assessed by the 6-minute walk distance (6MWD). Secondary outcomes included changes in CFR, serum NT-proBNP levels, quality of life (SF-36 Health Survey), and a composite of clinical cardiovascular events (all-cause mortality or heart failure hospitalization). (https://www.chictr.org.cn: ChiCTR2200067078). Over the 24-month follow-up, patients in the nicorandil group demonstrated a significantly greater improvement in exercise endurance, compared to the control group. This improvement was accompanied by significant enhancements in CFR, reductions in NT-proBNP levels, and higher quality-of-life scores. For the composite cardiovascular endpoint, a non-significant trend toward fewer events was observed in the nicorandil group (P=0.059). Nicorandil treatment was well-tolerated, and no serious adverse events were reported during the study period. In patients with HFpEF and concomitant CMD, nicorandil treatment demonstrated benefits by significantly improving exercise endurance, CFR, NT-proBNP levels, and quality of life.