Coronary Heart Disease: simvastatin decreased mortality.

Clinical bottom line (level 1b)

  1. Patients with coronary heart disease who were given simvastatin were less likely to die than those given placebo (NNT = 30 at 5.4 years) .
  2. Patients with coronary heart disease who were given simvastatin were less likely to have a major coronary event (NNT = 12 at 5.4 years) .
Scandinavian Simvastatin Survival Study Group : Lancet 1994; 344: 1383-1389
Expires December 2002

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 94 clinical centres, Scandinavia

4444 patients (aged range 35 to 70 years, 81% male) history of angina pectoris or acute myocardial infarction. After a two week placebo run-in, patients with serum cholesterol 5.5 to 8.0 mmol/l and serum triglyceride < or =2.5 mmol/l were randomised.

Excluded if
  • history of drug or alcohol abuse
  • poor mental function
  • other serious disorder
  • current treatment with another experimental drug
  • hypersensitivity to HMG-CoA reductase inhibitors
  • premenopausal women of childbearing potential
  • secondary hypercholesterolaemia
  • unstable or Prinzmetal angina
  • tendon xanthomata
  • planned coronary artery surgery or angioplasty
  • MI during the preceding 6 months
  • antiarrhythmic therapy
  • congestive heart failure requiring treatment with digitalis, diuretics or vasodilators
  • persistent atrial fibrillation
  • cardiomegaly
  • haemodynamically important valvular heart disease
  • history of completed stroke
  • impaired hepatic function
  • partial ileal bypass


    • Control Group: (n = 2223, 2223 analysed): placebo
    Experimental Group: (n = 2221, 2221 analysed): simvastatin 20 mg taken before the evening meal. Dose was adjusted, if necessary, at the 12 week and 6 month visits on the basis of serum total cholesterol at 6 and 18 weeks. The goal was to reduce serum total cholesterol to 3.0-5.2 mmol/l.

    100% followed for 5.4 years mean, with a range of 4.9-6.3 years.
    Outcome notes:
    • major coronary events : coronary death, nonfatal definite or probable MI, silent MI or resuscitated cardiac arrest

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    mortality 5.4 years 256
    (11.5%)    		 182
    (8.19%)    		 29.0%
    (15.0% to 41.0%)    		 3.32%
    (1.57% to 5.07%)    		 30
    (20 to 64)
    major coronary events 5.4 years 622
    (28.0%)    		 431
    (19.4%)    		 31.0%
    (23.0% to 28.0%)    		 8.57%
    (6.09% to 11.1%)    		 12
    (9 to 16)

  • Kaplan-Meier estimates of risk of death with simvastatin were 0.70 (95% CI 0.59 to 0.85)
  • Kaplan-Meier estimates of risk of major coronary events on simvastatin was 0.66 (95% CI 0.59 to 0.75)

    • Comments

    1. The study has limited power for women (n=500).
    2. 13% of patients in the placebo group and 10% in the simvastatin group stopped taking their tablets.

    Citation

    1. Scandinavian Simvastatin Survival Study Group , : Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389
    Contributor: Clare Wotton and Bob Phillips, December 1999
    Reviewer: Daniel Sontheimer

    Clinical Question.
    Patient coronary heart disease
    Intervention or Exposure simvastatin
    Comparison placebo
    Outcome mortality