Nicorandil in Heart Failure
Nicorandil is not recommended in standard heart failure management and is notably absent from all major international heart failure guidelines, including the most recent 2022 ACC/AHA/HFSA guidelines. The established first-line therapies for heart failure with reduced ejection fraction (HFrEF) remain ACE inhibitors or ARNIs, beta-blockers, aldosterone antagonists, and SGLT2 inhibitors 1.
Guideline-Based Standard Therapy
The evidence-based pharmacological management for heart failure prioritizes:
- ACE inhibitors or ARNIs as first-line renin-angiotensin system inhibition to reduce morbidity and mortality 1
- Beta-blockers (bisoprolol, carvedilol, or sustained-release metoprolol succinate) for all patients with current or prior HFrEF symptoms 1
- Aldosterone receptor antagonists for NYHA class II-IV patients with LVEF ≤35% 1
- Diuretics for fluid retention management 1, 2
The 2022 ACC/AHA/HFSA guidelines make no mention of nicorandil as a therapeutic option for any stage or type of heart failure 1. Similarly, the 2013 ACC/AHA guidelines 1, 2016 focused update 1, and NICE guidelines 1 do not include nicorandil in their treatment algorithms.
Research Evidence on Nicorandil
While nicorandil (a potassium channel opener with nitrate-like properties) is absent from guidelines, limited research suggests potential acute hemodynamic benefits:
Acute Hemodynamic Effects
- Intravenous nicorandil reduces pulmonary artery wedge pressure (PAWP) by 26.5% and increases cardiac index by 15.8% in acute decompensated heart failure (ADHF) patients 3
- Improves dyspnea scores and left ventricular diastolic function (E/e' ratio) within 1-24 hours of administration 4
- Decreases BNP levels significantly by day 3 in acute heart failure patients 5
Mid-Term Outcomes
- A 2014 meta-analysis of 20 studies (1,222 patients) showed nicorandil reduced all-cause mortality and cardiac hospitalization (HR: 0.35, P<0.001) in five randomized controlled trials 6
- A single observational study found 180-day event-free survival rates of 91.0% with nicorandil versus 76.8% without (P=0.006) 7
Critical Limitations
- A 2017 randomized controlled trial (n=106) demonstrated that while nicorandil improved acute symptoms and hemodynamics, it did not reduce 60-day all-cause mortality or readmission rates 4
- All studies are from Japanese populations with small sample sizes
- No long-term mortality benefit has been established in adequately powered trials
- Nicorandil has not been compared head-to-head with guideline-directed medical therapy
Clinical Bottom Line
Nicorandil should not replace or delay initiation of guideline-directed medical therapy 1. The cornerstone treatments—ACE inhibitors/ARNIs, beta-blockers, and aldosterone antagonists—have robust evidence from large international trials demonstrating mortality reduction 1.
When Nicorandil Might Be Considered (Off-Guideline)
If considering nicorandil in regions where it is available, it would only be as:
- An adjunctive acute vasodilator in ADHF when standard vasodilators (nitroglycerin) are contraindicated or ineffective 5, 3
- Never as monotherapy or replacement for evidence-based HF medications 1
Safety Considerations
- Can be administered safely even in patients with systolic blood pressure <140 mmHg without excessive hypotension 5, 3
- Does not cause significant reflex tachycardia 4
- Requires intravenous administration (0.2 mg/kg bolus followed by 0.2 mg/kg/h infusion) 3, 4
Key Pitfall to Avoid
Do not use nicorandil as a substitute for proven guideline-directed medical therapy. The absence of nicorandil from all major international guidelines reflects insufficient evidence for routine use, despite some promising acute hemodynamic data 1.