67TH SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION - Dallas, Texas - 17 November 1994

Lipid-Lowering Drug Reduces Mortality


Delegates to the 67th Scientific Sessions of the American Heart Association in Dallas learned today that, for the first time ever, a rigorously controlled clinical study has proven that a lipid-lowering drug can reduce the risk of death or non-fatal coronary events in people with established coronary heart disease (CHD).

The landmark Scandinavian Simvastatin Survival Study (4S Study) covered 4,444 subjects (20 percent of them women) in 94 centres throughout Norway, Sweden, Finland, Denmark, and Iceland. The randomized, double-blinded, placebo-controlled study started in 1988 and ran for 6 years. The results presented today by the study's coordinator, Dr. Terje R. Pedersen of Aker University Hospital, Oslo, showed significant reductions over the spectrum of mortality and morbidity for cardiac patients: 30-percent reduction in all-cause mortality; 42-percent reduction in mortality from CHD; 34-percent reduction in major CHD events; approximately 27-percent reduction in "softer" endpoints (e.g., hospitalization for chest pain); and 37-percent reduction in the need for coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angiography (PTCA).

These favorable results were seen throughout the major sub-groups included in the study, such as women and the elderly. The study also laid to rest fears that drug treatment to lower lipids causes depression and increases the risk of suicide, violent death, or death from cancer; such conditions occurred equally infrequently in the control group and the group treated with simvastatin.

Subjects enrolled in the 4S study ranged in age from 35-70 years. They all had established CHD and total cholesterol (TC) levels of 5.5 mmol/L or greater. They were initially given dietary advice; if, after two months of dietary therapy they had TC levels between 5.5-8.0 mmol/L, they were kept in the study and randomly assigned, in equal numbers, to placebo or simvastatin treatment. Initial simvastatin dosage was 20 mg once daily. If TC levels did not drop below 5.2 mmol/L after 6 weeks of drug therapy, dosage was increased to 40 mg once a day; subjects in the control group were also randomly given increased doses of placebo.

Treatment with simvastatin produced a marked change in lipid levels after only a short period; for example, after 6 weeks the mean reduction in TC was 28 percent. The most important effect was on low-density lipoprotein (LDL), but high-density lipoprotein (HDL) and triglycerides (TG) were also significantly favorably affected. Over the 6-year span of the trial, lipid fractions were affected as follows: TC reduced 25 percent, LDL reduced 35 percent, HDL elevated 8 percent, TG reduced 10 percent.

Compliance was excellent during the trial. Of those on placebo, 13 percent dropped out of the study; 10 percent of the simvastatin patients quit. Tolerance was also impressive: only 6 percent in either group (drug or placebo) dropped out due to adverse effects.

In an exclusive interview with us after his presentation, Dr. Pedersen commented on an unexpected finding that treatment with simvastatin reduced cerebrovascular events -- such as transient ischemic attacks (TlAs) and stroke -- by 30 percent. He noted that "we hadn't created an a priori hypothesis to study this, but [it] is a very interesting finding... promising, very promising."

He also pointed out that the results of the 4S trial could have an important socioeconomic impact: "We have demonstrated that if you treat 100 patients for 6 years with simvastatin, you will prevent 4 of the 9 anticipated deaths that otherwise would happen with standard therapy; it would also prevent 6 of the anticipated 19 bypass surgeries that would be needed; and we have shown that we would prevent 7 of the 21 hospitalizations that otherwise would happen -- hospitalizations because of acute myocardial infarction. So that carries a very significant result of great health economic consequences."