Intravenous nicorandil did not significantly reduce primary composite outcomes in patients with STEMITrial shows intravenous nicorandil does not improve heart attack outcomes

Journal of the American College of Cardiology Published September 16, 2026 Study authors: Huang Dong, Wu Hongxian, Lu Yuan, Liu Qingjun, Cai Haipeng, Shen Jieyan, Ma Likun, Yu Zongliang, Zha… PubMed ↗ NCT04665648 ↗ DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that intravenous nicorandil did not significantly improve primary outcomes in patients with STEMI.

This multicenter randomized controlled trial enrolled 1,503 patients aged 18 to 80 years presenting with ST-segment elevation myocardial infarction (STEMI) within 12 hours of symptom onset. Patients were randomized to receive either intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or a matching placebo.

The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. The results showed no significant difference between groups, with 13.1% (98) in the nicorandil group and 13.1% (99) in the placebo group reaching the primary endpoint (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429).

Secondary outcomes included cardiovascular death (HR: 0.515; 1.9% vs 3.6%; 95% CI: 0.269-0.983) and target-vessel revascularization (HR: 0.322; 1.1% vs 3.0%; 95% CI: 0.143-0.727). Rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between the nicorandil and placebo groups. Due to the lack of statistical significance in the primary outcome, the findings do not support the routine use of intravenous nicorandil in unselected patients with STEMI.

How this fits prior evidence

How this fits prior evidence: This trial addresses the management of STEMI patients, a condition also addressed in previous coverage regarding the use of high-dose statin preloading to reduce mortality, pressure optimization protocols to improve reperfusion, and adjunctive intracoronary thrombolysis to reduce major adverse cardiovascular events. While those interventions showed specific benefits, this study indicates that intravenous nicorandil does not provide a statistically significant reduction in the primary composite outcome for unselected STEMI patients.

When a person suffers a heart attack, every minute counts. Doctors are always looking for ways to improve survival and recovery during those critical first hours. One specific medication, nicorandil, was tested to see if it could help patients who had a serious type of heart attack called STEMI.

Researchers studied 1,503 patients across 49 hospitals. They gave one group the drug and another group a placebo. While the study did show a small decrease in the number of people needing procedures to reopen blocked vessels, the overall results were not significant. This means the drug did not perform better than a placebo in preventing major complications like death or heart failure over a 12-month period.

Because the primary results were not statistically significant, the study suggests that nicorandil is not currently recommended for routine use in patients with this type of heart attack. While the data is clear on the primary outcomes, the study notes that the drug was well tolerated and did not show different safety risks compared to the placebo.

What this means for you:

Nicorandil did not significantly improve primary outcomes for patients with a heart attack in this large trial.

Common questions

Does nicorandil help people who have a heart attack?

The study of 1,503 patients found that nicorandil did not significantly improve the primary outcome, which included death, heart failure, or the need for surgery. While there was a small decrease in the need for vessel revascularization, the overall results did not support using the drug for routine treatment of heart attacks.

Is nicorandil safe to use after a heart attack?

In this trial, the drug was well tolerated. There were no significant differences in adverse events between the group that received nicorandil and the group that received a placebo. However, because it did not improve primary outcomes, it is not recommended for routine use.

How many people were involved in this study?

The study was a large multicenter trial involving 1,503 patients between the ages of 18 and 80. These patients were treated within 12 hours of their heart attack symptoms starting.

Study Details

Study typeRct

Sample sizen = 748

EvidenceLevel 2

Follow-up12.0 mo

PublishedSep 2026

PMID42584383

TrialNCT04665648

View Original Abstract ↓

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Intravenous nicorandil did not significantly reduce primary composite outcomes in patients with STEMITrial shows intravenous nicorandil does not improve heart attack outcomes

How this fits prior evidence

Common questions

Study Details

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Intravenous nicorandil did not significantly reduce primary composite outcomes in patients with STEMITrial shows intravenous nicorandil does not improve heart attack outcomes

How this fits prior evidence

Common questions

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Study Details

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