Routine intravenous nicorandil in primary PCI did not improve one-year outcomes

Design

Multicentre, randomised, double-blind, placebo-controlled trial

Population

1,503 patients with STEMI within 12 hours undergoing primary PCI, 49 Chinese hospitals

Primary outcome

CV death, non-fatal MI, TVR or HF hospitalisation at 12 months

Effect

13.1% vs 13.1% of patients; total-event rate ratio 0.87 (95% CI 0.65-1.16)

CLEAN randomised 1,503 patients aged 18 to 80 with STEMI within 12 hours at 49 Chinese hospitals to intravenous nicorandil (6 mg bolus before reperfusion, then 6 mg/h for 48 hours) or matching placebo, double blind. Oral nicorandil was not allowed afterwards.

The primary composite of cardiovascular death, non-fatal infarction, target vessel revascularisation or unplanned heart failure admission at one year occurred in 13.1% of patients in both groups (rate ratio for total events 0.87, 95% CI 0.65 to 1.16). Cardiovascular death (1.9% vs 3.6%) and target vessel revascularisation (1.1% vs 3.0%) were lower with nicorandil, but these were secondary endpoints and the authors call them nominal. Adverse events were similar.

Nicorandil is widely used in Indian cath labs to treat or prevent no-reflow. This trial does not address its use as a rescue for established no-reflow, but it gives no support for giving it routinely to every patient.

• Do not add intravenous nicorandil routinely to primary PCI for STEMI.
• Treat the lower cardiovascular death rate as a hypothesis for a future trial, not a reason to use it.
• Its use as rescue therapy for established no-reflow was not tested here and remains a separate decision.
• Put effort into the measures with proven benefit: door-to-balloon time, radial access and full secondary prevention.

Why it matters

A widely used adjunct in Indian cath labs now has a large blinded trial showing no overall benefit.

Don't overread it

The lower cardiovascular death rate was a secondary finding in a neutral trial and should not guide practice.

The statistics, in plain English

A rate ratio for total events of 0.87, with a confidence interval from 0.65 to 1.16, is compatible with a 35% lower or a 16% higher event rate, so the trial cannot confirm any effect. Secondary endpoints that look significant in a trial whose primary endpoint failed are often chance findings, because many outcomes were examined.

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