Unstable angina or MI: role of calcium-channel blockers is unclear.

Clinical bottom line (level 1a)

  1. There is no clear benefit in giving dihydropyridine calcium blockers (nifedipine and nicardipine) to patients with unstable angina or MI- it may well be harmful.
  2. Calcium antagonists that slow heart rate (verapamil, diltiazem) reduce reinfarction (NNT = 68 at 2days-6 weeks) , but the effect on mortality is unclear.
Held et al: British Medical Journal 1989; 299: 1187-1192
Yusuf et al: American Journal of Cardiology 1991; 67: 1295-1297
Expires March 2003

The study

Systematic review of randomised controlled trials of
  • Patients: unstable angina or suspected or proven myocardial infarction
  • Intervention: calcium channel blockers compared with control
  • Outcome: mortality


    • Articles found in all using not stated, before Jan 1989 (search terms: not detailed ) and bibliographies were also searched, authors and experts contacted for unpublished studies or other relevant articles

    Selection criteria: as above
    Appraisal criteria: not detailed
    Articles excluded if: patients were excluded if they had:
    • low systolic blood pressure
    • low or high heart rate, 45-60 or 110-120 beats/min
    • severe heart failure or shock
    • atrioventricular block


    twenty-two randomised controlled trials; sixteen double-blind, four single-blind; ~18,000 patients, most with suspected MI- 1100 with unstable angina
    • Patients received one of:
      • verapamil 320-360 mg po daily (3,500 patients)
      • nifedipine 30-120 mg po daily (9,700 patients)
      • diltiazem 120-360 mg po daily (3,100 patients)
      • lidoflazine 180-240 mg po daily (1,800 patients)
    • In six studies, medication was given intravenously. Calcium channel blockers were usually compared with placebo, though in three trials for unstable angina, they were compared with propranolol.
    • Patients were followed for 24 hours to six weeks in acute trials, and one to six years medium to long-term trials.
    There was no significant heterogeneity found.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    death in acute short-term trials 2days-6 weeks 210/3195
    (6.57%)    		 1.11
    (0.90 to 1.36)     		-150
    (NNT = 162 to infinity;
    NNH = 46 to infinity)
    death in long-term trials 1-6 years 873/8870
    (9.84%)    		 1.03
    (0.89 to 1.20)     		-380
    (NNT = 100 to infinity;
    NNH = 57 to infinity)
    reinfarction with medication started within 24 hours 2days- years 3364/5431
    (61.9%)    		 0.97
    (0.90 to 1.06)     		140
    (NNT = 40 to infinity;
    NNH = 73 to infinity)
    death in unstable angina 2days-6 weeks 9/578
    (1.56%)    		 1.53
    (0.66 to 3.57)     		-120
    (NNT = 190 to infinity;
    NNH = 26 to infinity)
    reinfarction in unstable angina 2days-6 weeks 104/548
    (19.0%)    		 1.04
    (0.77 to 1.40)     		-160
    (NNT = 27 to infinity;
    NNH = 17 to infinity)
    death with dihydropyridine calcium blockers 2days-6 weeks 335/5135
    (6.5%)    		 1.16
    (0.99 to 1.35)     		-100
    (NNT = 1640 to infinity;
    NNH = 48 to infinity)
    reinfarction with dihydropyridine calcium blockers 2days-6 weeks 119/3871
    (3.1%)    		 1.19
    (0.92 to 1.53)     		-180
    (NNT = 420 to infinity;
    NNH = 64 to infinity)
    death with calcium antagonists that slow heart rate 2days-6 weeks 447/4226
    (10.6%)    		 0.95
    (0.82 to 1.09)     		210
    (NNT = 58 to infinity;
    NNH = 120 to infinity)
    reinfarction with calcium antagonists that slow heart rate 2days-6 weeks 313/4184
    (7.5%)    		 0.79
    (0.67 to 0.94)     		68
    (43 to 240)

    Comments

    1. Large variation in methods, controls, outcome measures and follow-up. No details of how these have been weighted and combined- reduces validity of this overview.

    Citation

    1. Held PH, Yusuf S, Furberg CD: Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. British Medical Journal 1989; 299: 1187-1192
    2. Yusuf S, et al: The effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. American Journal of Cardiology 1991; 67: 1295-1297
    Search Terms: unstable and angin* and (calcium-channel or verapamil or diltiazem or nifedipine) in Cochrane
    Contributor: Nick Shenker, Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient unstable angina or suspected MI
    Intervention or Exposure calcium channel blockers
    Outcome mortality