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Subgroup Analyses in the Scandinavian Simvastatin Survival Study

Steven M. Haffner, MD; Charles M. Alexander, MD; Thomas J. Cook, MS; Stephen J. Boccuzzi, PhD; Thomas A. Musliner, MD; Terje R. Pedersen, MD; John Kjekshus, MD; Kalevi Pyörälä, MD; for the Scandinavian Simvastatin Survival Study Group

Arch Intern Med. 1999;159:2661-2667.

Background  Patients with diabetes mellitus (DM) have a marked increase in coronary heart disease (CHD) events relative to those without DM. In a previous report from the Scandinavian Simvastatin Survival Study using a clinical case definition of DM (n = 202), simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects.

Objective  To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels.

Methods  Using the 1997 American Diabetes Association diagnostic criteria, we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Scandinavian Simvastatin Survival Study patients with normal fasting glucose (n = 3237), impaired fasting glucose (n = 678), and DM (n = 483).

Results  Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). Total (RR = 0.79; P = .34) and coronary (RR = 0.72; P = .26) mortality were also reduced in DM, but not significantly, due to small sample size. In impaired fasting glucose (IFG) subjects, simvastatin use significantly reduced the number of major coronary events (RR = 0.62; P = .003), revascularizations (RR = 0.57; P = .009), and total (RR = 0.57; P = .02) and coronary (RR = 0.45; P = .007) mortality.

Conclusions  Our results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels ( 6.0 mmol/L [ 110 mg/dL]) or DM and known CHD.

From the Department of Medicine, University of Texas Health Science Center at San Antonio (Dr Haffner); US Medical & Scientific Affairs, Merck & Co Inc, West Point, Pa (Drs Alexander and Boccuzzi); Merck Research Laboratories, Rahway, NJ (Mr Cook and Dr Musliner); Cardiology Section, Medical Department, Aker Hospital (Dr Pedersen), and Section of Cardiology, Rikshospitalet (Dr Kjekshus), Oslo, Norway; and Department of Medicine, University of Kuopio, Kuopio, Finland (Dr Pyörälä). A list of members of the Scandinavian Simvastatin Survival Study Group appears in the Lancet, 1994;344:1388-1389.

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