Cholesterol Lowering With Simvastatin Improves Prognosis of Diabetic Patients With Coronary Heart Disease: A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S)

  1. The Scandinavian Simvastatin Survival Study (4S) Group
  1. Department of Medicine, National University Hospital Reykjavik, Iceland
  2. University of Kuopio Kuopio, Finland Medical Clinic, National University Hospital Reykjavik, Iceland
  3. Aker Hospital, Department of Medicine, National University Hospital Reykjavik, Iceland
  4. Rikshospitalet, Oslo, Norway Department of Medicine and Cardiology, National University Hospital Reykjavik, Iceland
  5. Århus Amtssygehus University Hospital Århus, Denmark Department of Internal Medicine, National University Hospital Reykjavik, Iceland
  6. Linköping University Hospital Linköping, Sweden Department of Medicine, National University Hospital Reykjavik, Iceland
  1. Address correspondence and reprint requests to Kalevi Pyörälä, MD, Department of Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.

Abstract

OBJECTIVE To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events.

RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5–8.0 mmol/l, and serum triglycerides ≤ 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6–18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures.

RESULTS Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30–1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27–0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43–0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58–0.87; P = 0.001), 0.68 (95% CI, 0.60–0.77; P < 0.0001), and 0.74 (95% CI, 0.68–0.82; P < 0.0001).

CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.

  • Received September 17, 1996.
  • Accepted December 31, 1996.
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