Nicorandil significantly improved exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) and coronary microvascular dysfunction (CMD), according to a randomised controlled trial that also reported improvements in coronary blood flow, biomarkers, and quality of life over 24 months.
Assessing Nicorandil in Heart Failure
Researchers enrolled 113 patients with HFpEF and CMD in a single-centre, randomised controlled trial. Participants were assigned to receive either oral nicorandil alongside usual treatment (n=57) or usual treatment alone (n=56). Nicorandil was administered at 5 mg three times daily, and patients were followed up for 24 months.
Eligible participants had no significant narrowing of the major coronary arteries and had CMD, defined as a coronary flow reserve (CFR) below 2.0.
The primary outcome was change in exercise capacity, assessed using the 6-minute walk distance (6MWD). Secondary outcomes included CFR, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, quality of life, and a composite of all-cause mortality or hospitalisation for heart failure.
Exercise Capacity and Quality of Life Improve
After 24 months, patients receiving nicorandil experienced a significantly greater improvement in 6MWD than those receiving usual treatment alone. Walking distance increased by a mean of 38.6 metres in the nicorandil group, compared with 13.5 metres in the control group.
Nicorandil was also associated with improvements in coronary microcirculation. At 24 months, mean CFR was 2.10 in the nicorandil group and 1.85 in the control group (p<0.001). Patients receiving nicorandil also had significantly greater reductions in NT-proBNP levels and higher physical and mental quality-of-life scores.
Larger Studies Needed to Confirm Findings
Nicorandil was generally well tolerated during follow-up. One patient discontinued treatment because of headache and dizziness, which resolved after the medication was withdrawn. No serious adverse reactions were reported.
Researchers concluded that nicorandil improved exercise capacity, coronary microcirculation, NT-proBNP levels, and quality of life in patients with HFpEF and CMD. They suggested that these benefits may be associated with more favourable cardiovascular outcomes.
However, the study’s small sample size, single-centre design, and limited follow-up period restrict the conclusions that can be drawn, particularly regarding cardiovascular events. Researchers called for larger, multicentre studies to validate the findings.
Reference
Gu J et al. Beneficial effects of nicorandil on exercise capacity in heart failure with preserved ejection fraction patients with concomitant coronary microvascular dysfunction. Hellenic J Cardiol. 2026.DOI; 10.1016/j.hjc.2026.10.003.
