Investigators reported a large, randomized, five-year study including more than 20,000 individuals at high cardiovascular risk. Treatment with the lipid lowering drug simvastatin 40 mg/day reduced the incidence of major vascular events by one-third. Surprisingly, even individuals with low cholesterol had a treatment benefit of this magnitude. Antioxidant vitamin supplementation did not reduce major vascular events.

The long-term benefits of a cholesterol-lowering drug therapy are uncertain for patients at high risk of cardiovascular disease. Another unresolved question is whether antioxidant vitamin supplementation helps or harms these patients.

The Heart Protection Study addressed these questions in a cohort of 20,536 patients from 69 centers. Investigators randomized patients to simvastatin 40 mg/day or placebo. In addition, they allocated half of each patient group to receive a vitamin cocktail (vitamin E, vitamin C, and beta-carotene) or placebo capsules.

They enrolled a wide range of high-risk patients, including those with coronary disease, other occlusive arterial disease, diabetes, and hypertension. This population included many women, elderly individuals, and patients with acceptable cholesterol levels. Little data exists regarding the value of treatment for these groups.

Despite 5.5 years of treatment, vitamins provided no clinical benefit, although there was no evidence of harm. The conclusion is that these patients can take vitamins, if they wish, without worrying about safety.

Statin treatment resulted in large mean reductions in serum total cholesterol levels (1.3 mmol/L) and LDL cholesterol (1.0 mmol/L). Remarkably, cholesterol-lowering therapy reduced the risk of major vascular events by at least one-quarter for every patient group (that reduction was actually one-third when non-compliant patients were excluded).

The Heart Protection Study showed for the first time definitive evidence that statin therapy is beneficial in patients with diabetes, even if they did not have substantial risk of coronary heart disease.

It is also the first large study of a cholesterol-lowering regime in women (about 5,000 women participated in the study). According to Dr. Collins, physicians now have direct evidence that statins reduce the risk of events by at least one-third in women.

Perhaps the most remarkable finding is that these high-risk individuals had a benefit regardless of their serum cholesterol level. Investigators observed a reduction in vascular events of at least one-third for both low-to-normal and high cholesterol patient groups.

This finding could have enormous policy implications. Experts at the AHA meeting said that perhaps physicians should not wait to initiate cholesterol lowering at specific targets levels of serum cholesterol. Instead, they could begin treatment of high-risk patients irrespective of starting cholesterol level. This approach would simplify therapy enormously.