Issue 112 Item 4 Simvastatin Lowers CV Risk and Mortality Regardless of Levels

This information could save about 50,000 lives a year — that is, a thousand each week.” Simvastatin, but not antioxidants, lowered cardiovascular (CV) risk and mortality in the Heart Protection Study (HPS), that, according to two reports in the July 6 issue of The Lancet. The benefit of simvastatin was proportional to the CV risk, not to the baseline cholesterol concentration.

"HPS shows unequivocally that statins can produce substantial benefit in a very much wider range of high-risk people than had been previously thought," investigator Rory Collins, from the University of Oxford in England, says in a news release. "These new findings are relevant to the treatment of some hundreds of millions of people worldwide."

The HPS randomized 20,536 adults in the United Kingdom to receive daily placebo, simvastatin 40 mg, or antioxidant supplementation with 600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene for five years. Subjects were 40 to 80 years of age and had coronary artery disease, other occlusive arterial disease, or diabetes.

Death from all causes was 12.9% for patients given simvastatin, 14.7% for patients given placebo, and 14.1% for patients given antioxidants (P=.0003 for simvastatin vs. placebo). The reduced mortality for patients receiving simvastatin was primarily related to an 18% relative reduction in the coronary death rate from 6.9% (707 deaths) for patients receiving placebo to 5.7% (587 deaths) to patients receiving simvastatin (P=.0006).

"If, as a result [of these findings], an extra 10 million high-risk people were to go onto statin treatment, this would save about 50,000 lives a year — that is, a thousand each week," Collins says. "In addition, this would prevent similar numbers of people from suffering non-fatal heart attack or stroke."

Relative reductions in patients receiving simvastatin were about 25% for nonfatal myocardial infarction or coronary death, for nonfatal or fatal stroke, and for coronary or noncoronary revascularization. Simvastatin was well tolerated with no major adverse effects, although the annual excess risk of myopathy was 0.01%. Its benefits did not depend on baseline lipid levels and were synergistic with those of other cardioprotective treatments including aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors.

Antioxidant supplementation was not linked to any significant reductions in the five-year risk of myocardial infarction, stroke, cancer or other major outcomes.

"These findings should tear up the rule-book on statin prescribing," says Richard Horton, editor of The Lancet. "They are the most important and far-reaching results for the treatment and prevention of heart disease and stroke that we have seen in a generation. They should result in a dramatic change in clinical practice around the world. Previously there has been concern that statins have been used too much; after the results of HPS have been published there should be concern that they may not be used enough in the future." Merck & Co. helped support this study. Lancet. 2002;360:7-22, 23-33