Effect of statins on mortality and cardiovascular events in elderly high-risk persons.

Abstract

Review of: MRC/BHF Heart Protection Study of Cholesterol Lowering with Simvastatin in 20,536 High-Risk Individuals: a Randomized Placebo-Controlled Trial. Lancet 2002;360:7–22. PURPOSE: To determine the effect of simvastatin 40 mg daily versus placebo on all-cause mortality and cardiovascular events in high-risk persons with serum total cholesterol levels of 135 mg/dL or greater. BACKGROUND: Pooled data from three secondary prevention trials of patients with coronary artery disease (CAD) and two primary prevention studies showed that treatment of hypercholesterolemia with statins caused a 31% reduction in major coronary events (95% confidence interval (CI) = 26–36%) and a 21% reduction in all-cause mortality (95% CI = 14–28%).1 The secondary prevention trials included 4,444 persons (23% aged 65–70) treated with simvastatin in the Scandinavian Simvastatin Survival Study,2,3 4,159 persons (31% aged 65–75) treated with pravastatin in the Cholesterol and Recurrent Events Trial,4–6 and 9,014 persons (39% aged 65–75) treated with pravastatin in the long-term Intervention with Pravastatin in Ischaemic Disease Trial.7 The two primary prevention studies included 6,595 middle-aged men up to 64 years of age treated with pravastatin in the West of Scotland Coronary Prevention Study8 and 6,605 persons (22% aged 65–73) treated with lovastatin in the Air Force/Texas Coronary Atherosclerosis Prevention Study.9 The absolute risk reduction in major coronary events per 1,000 persons treated in these five studies was 33 (13–52) for women versus 37 (29–44) for men and 44 (30–58) for persons aged 65 and older versus 32 (24–40) for younger persons.1 METHODS: The Heart Protection Study included 20,536 persons (15,454 men and 5,082 women) aged 40 to 80 (5,806 aged 70–80) with serum total cholesterol of 135 mg/dL or greater and prior myocardial infarction (MI) (8,510 persons), other CAD (4,876 persons), or no CAD (7,150 persons). Of the 7,150 participants without CAD, 1,820 had cerebrovascular disease, 2,701 had peripheral arterial disease (PAD), and 3,982 had diabetes mellitus. Although treated hypertension was present in 8,457 persons, only 237 persons were included on the basis of hypertension alone. Patients were randomized to simvastatin 40 mg daily or double-blind placebo. Mean follow-up was 5 years. Average compliance was 85% for the simvastatin-treated group, and 17% of the placebo group took a statin during the 5-year study. RESULTS: During the 5-year study, simvastatin reduced serum total cholesterol 46 mg/dL, serum low-density lipoprotein (LDL) cholesterol 39 mg/dL, and serum triglycerides 12 mg/dL and increased serum high-density lipoprotein (HDL) cholesterol 1 mg/dL Simvastatin caused a 13% reduction in all-cause mortality (95% CI = 6–19%), a 17% reduction in any vascular death (95% CI = 9–25%), a 27% reduction in major coronary events (95% CI = 21–33%), a 25% reduction in any stroke (95% CI = 15–34%), a 24% reduction in coronary or noncoronary revascularization (95% CI = 17–30%), and a 24% reduction in any major vascular event (95% CI = 19–28%). Simvastatin significantly reduced the first major vascular event in patients with MI, other CAD, or no CAD; in patients with cerebrovascular disease, PAD, diabetes mellitus, treated hypertension, or no hypertension; in men and in women; in patients aged 40 to 64, 65 to 69, and 70 to 80; in patients with low or high serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides; in smokers and nonsmokers; and in patients treated with and without aspirin, beta blockers, and angiotensin-converting enzyme inhibitors. In the 3,500 persons with an initial serum LDL cholesterol of less than 100 mg/dL, reduction of serum LDL cholesterol from 97 mg/dL to 65 mg/dL by simvastatin caused a similar reduction in risk, as did treating patients with higher serum LDL cholesterol levels. Five years of simvastatin therapy prevented MI, stroke, and revascularization in 70 to 100 per 1,000 treated patients. CONCLUSION: In patients with serum total cholesterol of 135 mg/dL or higher at high risk for vascular events, simvastatin 40 mg daily significantly reduced all-cause mortality, vascular death, major coronary events, coronary or noncoronary revascularization, and any major vascular event regardless of initial levels of serum lipids, age, or gender.