An estimated 150 million persons worldwide have diabetes, and the prevalence is expected to double by 2025. Cardiovascular conditions, especially stroke and myocardial infarction, are the major causes of morbidity and mortality in these persons. Conventional lipid-lowering treatments are underused in patients with diabetes because blood levels of cholesterol and low-density lipoprotein (LDL) cholesterol tend to be within normal ranges. In addition, studies of lipid-lowering drugs have included relatively few patients with diabetes, making the effect of these drugs on this population difficult to determine. The British Heart Protection Study used a large, prospective, placebo-controlled clinical trial to assess the effect of substantial LDL cholesterol reduction by simvastatin on vascular morbidity and mortality in patients with diabetes.
They studied nearly 6,000 adults 40 to 80 years of age who had confirmed clinical diabetes, nonfasting cholesterol levels of at least 135 mg per dL (3.5 mmol per L), and coronary disease or noncoronary occlusive vascular disease. Men with diabetes who were 65 years or older and who had treated hypertension also were eligible for the study. Exclusions included recent myocardial infarction; stroke or hospital admission for angina; chronic hepatic, renal, or muscular disease; contraindications to statin therapy; or clear indications for statin therapy.
Following intake assessment and a run-in phase of four weeks of placebo followed by four to six weeks of treatment with 40 mg of simvastatin, eligible patients were randomly assigned to treatment with simvastatin (in a dosage of 40 mg daily) or an identical placebo. Patients returned for monitoring at four, eight, and 12 months, then every six months for a mean of 4.8 years. Blood samples were drawn at these visits for a lipid profile, evidence of hepatic or muscle damage, and glucose control (A1c). Information was gathered from patients and physicians about any confirmed or suspected serious illness or adverse reaction to study drugs. Events were confirmed by hospital and death certificate data. The major outcomes monitored were first major coronary event and first major vascular event.
Adherence to simvastatin therapy was estimated at 82 percent. In all patients, allocation to simvastatin was associated with a significant 27 percent reduction in first myocardial infarction or coronary death. In patients with diabetes, coronary mortality was 6.5 percent in those treated with simvastatin, significantly lower than the 8 percent in those given placebo. The reduction in first nonfatal myocardial infarction was even more significantly reduced: 3.5 percent in patients with diabetes who were treated with simvastatin compared with 5.5 percent in those given placebo.
Stroke was also significantly reduced in patients treated with simvastatin, with highly significant reductions in patients with diabetes. The authors calculate a 28 percent reduction in ischemic stokes in patients treated with simvastatin compared with patients given placebo. A 17 percent reduction also was noted in first revascularization procedures in patients treated with simvastatin. Overall, a 24 percent reduction was found in first occurrence of any of the major vascular outcomes in patients with diabetes who were receiving simvastatin. Approximately one fourth of the patients who were taking placebo suffered a first vascular event during the five years of follow-up. The comparable rate was 20 percent in those treated with simvastatin.
The authors conclude that daily treatment with 40 mg of simvastatin reduces the number of first major vascular events in patients with diabetes by about one third to one fourth, even if patients had no evidence of coronary disease or hypercholesterolemia. They calculate that treating 1,000 patients with diabetes for five years would prevent 70 events in 45 patients.
editor's note: Although all other studies have not demonstrated comparable reductions in cardiovascular outcomes, the authors of this study call for consideration of statin therapy in all patients with type 2 diabetes, regardless of cholesterol levels.—A.D.W.