Intravenous Administration of Nicorandil Immediately Before Percutaneous Coronary Intervention Can Prevent Slow Coronary Flow Phenomenon - Intravenous Administration of Nicorandil Immediately Before Percutaneous Coronary Intervention Can Prevent Slow Coronary Flow Phenomenon


The goal of the trial was to evaluate treatment with nicorandil, a hybrid adenosine triphosphate-sensitive potassium channel (KATP) activator and vascular smooth muscle relaxant, in patients undergoing percutaneous coronary intervention (PCI).


Intravenous administration of nicorandil prior to PCI would be safe and effective in preventing slow coronary flow (SCF) phenomenon and no-reflow, and would reduce the incidence of adverse cardiovascular events following PCI.

Study Design

Study Design:

Patients Enrolled: 408
Mean Follow Up: 12 months
Mean Patient Age: 72
Female: 24%

Patient Populations:

Patients undergoing PCI were stratified into ACS and non-ACS groups, as follows:

  • ACS: Criteria for AMI
    • Chest pain lasting >30 minutes but less than 24 hours, ST-segment elevation in at least two contiguous electrocardiogram leads, and CK >2 times the upper limit of normal
  • ACS: Criteria for unstable angina
    • Typical angina at rest, angiographic evidence of a coronary stenosis >75%, and no increase in CK level
  • Non-ACS: Criteria for stable angina
    • Typical angina only with activity and angiographic evidence of a coronary stenosis >75%


    • Systolic blood pressure <80 mm Hg
    • Patients treated with a thrombus aspiration device
    • Prior coronary artery bypass grafting
    • Prior PCI during the study period

    Primary Endpoints:

    • Incidence of post-procedure slow coronary flow phenomenon (SCF) and no-reflow phenomenon immediately after stent placement

    Secondary Endpoints:

    • Incidence of post-procedure SCF and no-reflow in the ACS and non-ACS subgroups
    • cTFC
    • Maximum CK and CK-MB levels in patients with AMI
    • Target vessel revascularization
    • MACE, including death and unplanned hospitalization for congestive heart failure at 12 months

    Drug/Procedures Used:

    Patients with coronary artery disease undergoing PCI were stratified according to acute coronary syndrome (ACS) (n = 108) or non-ACS (n = 300), and randomized to treatment with 6 mg intravenous nicorandil (n = 206, 47 with ACS and 159 with non-ACS) or placebo (n = 202, 61 with ACS and 141 with non-ACS) prior to stent placement.

    Concomitant Medications:

    All patients were treated with heparin (100 U/kg) after arterial access was obtained. Additional heparin was given if the procedure lasted >60 minutes. All patients were treated with 2-5 mg intracoronary isosorbide dinitrate prior to initial angiography. No patients received thrombolytics, glycoprotein IIb/IIIa inhibitors, verapamil, or adenosine. Treatment with aspirin and ticlopidine was recommended prior to PCI in all stable patients, and at the time of urgent PCI in unstable patients.

Principal Findings:

Corrected TIMI frame count (cTFC) was significantly lower in both ACS and non-ACS patients treated with nicorandil. The incidence of post-PCI SCF (cTFC >20 frames) was also significantly lower in patients treated with nicorandil (4.4% vs. 17.8%, p < 0.0001), and consistent in both the ACS (4.3% vs. 26.2%, p = 0.003) and non-ACS (4.4% vs. 14.2%, p = 0.004) subgroups. In patients with acute myocardial infarction (AMI), peak creatine kinase (CK) and CK-myocardial band (CK-MB) levels were significantly lower in patients treated with nicorandil (1767 ± 1272 vs. 2974 ± 2484 IU/ml and 166 ± 122 vs. 260 ± 180 IU/ml, respectively, p = 0.02 for both comparisons). However, there was no reduction in incidence of major adverse cardiac events (MACE) at 12 months with nicorandil therapy. No cases of no-flow phenomenon were observed in this study.


The results of this study suggest that administration of intravenous nicorandil prior to PCI may reduce the incidence of SCF in both the ACS and non-ACS populations. However, this patient population was likely undertreated in terms of statin and glycoprotein IIb/IIIa inhibitor use, and this study was underpowered to evaluate long-term clinical endpoints. Furthermore, it is unclear from this study whether treatment with nicorandil is superior to the use of other vasodilators, such as verapamil, adenosine, and nitroprusside, in preventing SCF. This concept should be evaluated in larger-scale randomized clinical trials.


Kawai Y, Hisamatsu K, Matsbara H, et al. Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon. Eur Heart J 2009;Mar 10:[Epub ahead of print].

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, EP Basic Science, Lipid Metabolism, Chronic Angina

Keywords: Myocardial Infarction, Potassium Channels, Creatine Kinase, Nitroprusside, Angina, Stable, Nicorandil, Heparin, Electrocardiography, Angioplasty, Balloon, Coronary, Vasodilator Agents, Stents, Coronary Stenosis, Verapamil, Muscle, Smooth, Vascular

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