Unstable angina: nifedipine with propranolol and long-acting nitrates reduced death, MI and surgery.

Clinical bottom line (level 1b)

  1. In patients with unstable angina, adding nifedipine to propranolol and long-acting nitrates reduced subsequent sudden deaths, MI or recurrent angina requiring surgery (NNT = 6 at 4 months) .
  2. There was no clear difference in side effects.
Gerstenblith et al: New England Journal of Medicine 1982; 306 (15): 885-889
Expires June 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: university hospital, USA

138 patients (aged range 38 to 87 years; mean 61, 64% male) unstable angina (defined as chest pain at rest, and accompanied by transient ECG changes- ST elevation or depression, T-wave changes or arrhythmia)

Excluded if
  • aged <21 or >90
  • MI (elevation in CK to twice normal)
  • systolic blood pressure <90 mmHg
  • PR interval = 0.24 seconds
  • history of CABG or valvular or congenital heart abnormalities
  • symptomatic cerebrovascular disease


    • Control Group: (n = 70, 70 analysed): placebo
    Experimental Group: (n = 68, 68 analysed): nifedipine 10 mg po every six hours, increased to 20 mg po every six hours if no adverse effects
    All patients were treated with propranolol 40 mg po once daily or higher, and long-acting nitrates (minimum of 2.5 cm of topical preparation or 10 mg po) unless there was a contraindication. Patients had oxygen, limited ambulation and low-dose sedatives.
    91% followed for 4 months
    Outcome notes:
    • failure of medical therapy : sudden death, MI or eprsistent angina requiring surgery
    • side effects : requiring termination of medication- headaches or hypertension

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    failure of medical therapy 4 months 43
    (61.4%)    		 40
    (58.8%)    		 4%
    (-26% to 27%)    		 2.61%
    (-13.7% to 18.9%)    		 38
    (NNT = 5 to infinity;
    NNH = 7 to infinity)
    side effects 4 months 1
    (1.43%)    		 4
    (5.88%)    		 -312%
    (-3491% to 53%)    		 -4.45%
    (-10.7% to 1.79%)    		 -22
    (NNT = 56 to infinity;
    NNH = 9 to infinity)

    Comments

    1. The HINT study indicated that nifedipine should not be given alone to patients with unstable angina- an increase in mortality was noted in patients that were thus treated.
    2. The study used a pharmaceutical formulation of nifedipine which is now considered obsolete. Extended release calcium antagonists may be safer.

    Citation

    1. Gerstenblith G, Ouyang P, Achuff SC, et al: Nifedipine in unstable angina: a double-blind randomized controlled trial. New England Journal of Medicine 1982; 306 (15): 885-889
    Search Terms: unstable angina and nifedip* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Richard Koopmans

    Clinical Question.
    Patient angina
    Intervention or Exposure nifedipine
    Comparison placebo
    Outcome treatment failure