Unstable angina: nicorandil reduced chest pain in patients on maximal therapy.

Clinical bottom line (level 1b)

  1. Patients with unstable angina on maximal therapy who took nicorandil compared with placebo had fewer episodes of chest pain (NNT = 6 at 2 days) .
  2. The effect on subsequent MI or mortality was unclear.
Patel et al: European Heart Journal 1999; 20 (1): 51-57
Expires June 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: fourteen acute hospitals, UK

200 patients (aged mean 59 years, 68% male) admitted with unstable angina (new angina = one month, acceleration of previous angina, angina at rest or at night)

Excluded if
  • <30 or >80 years old
  • acute MI, non-Q wave MI, angina within one month of MI
  • uninterpretable ECG, eg. left bundle branch block. left ventricular hypertrophy and strain or digoxin effect
  • severe hypotension
  • known contraindication to nicorandil
  • secondary angina
  • CABG or PTCA in last three months
  • known arrhythmia
  • valvular heart defect
  • women of child-bearing age


    • Control Group: (n = 104, 104 analysed): placebo
    Experimental Group: (n = 96, 96 analysed): nicorandil 20 mg po twice daily for at least 48 hours (up to 28 days)
    All patients had aspirin 150 mg po once daily, atenolol 50-100 mg po once daily or metoprolol 12.5-50 mg po once daily, and diltiazem 180-360 mg. iv heparin and nitrates were used as required.
    100% followed for 2 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    2 days 38
    (36.5%)    		 20
    (20.8%)    		 43%
    (9% to 64%)    		 15.7%
    (3.39% to 28.0%)    		 6
    (4 to 29)
    MI or death 2 days 2
    (1.92%)    		 0
    (0.00%)    		 100%
    (% to %)    		 1.92%
    (-0.72% to 4.56%)    		 52
    (NNT = 22 to infinity;
    NNH = 140 to infinity)

    Comments

    1. Follow-up is too short and the study is too small to exclude any effect on subsequent MI or death.
    2. The significance of the Holter-derived endpoints, while interesting, does not justify using this agent until effects on harder clinical endpoints can be established
    3. This drug offers the potential to provide "chemical preconditioning" by rendering myocardial cells more resistant to ischemia through a number of possible (but incompletely defined) mechanisms.

    Citation

    1. Patel DJ, Purcell HJ, Fox KM: Cardioprotection by opening of the KATP channels in unstable angina. Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. European Heart Journal 1999; 20 (1): 51-57
    Search Terms: hand search
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Steven Borzak

    Clinical Question.
    Patient unstable angina
    Intervention or Exposure nicorandil
    Comparison placebo
    Outcome recurrent chest pain, MI, death