WOSCOPS (West of Scotland Coronary Prevention Study)

Statin trials through the early 1990s enrolled patients who had already had a myocardial infarction or who had established coronary artery disease. That made sense as a starting point, but it left the larger population of people with high cholesterol and no prior cardiac event without clear guidance. Clinicians who wanted to prescribe pravastatin to an asymptomatic patient with an LDL of 5 mmol/L had no large outcome trial to cite.

The West of Scotland Coronary Prevention Study screened about 81,000 men in the west of Scotland. Between 1989 and 1991 it enrolled 6,595 aged 45 to 64 with a mean LDL cholesterol of 5.0 mmol/L (192 mg/dL) and no history of myocardial infarction. James Shepherd of the University of Glasgow, whose interest in primary prevention began on the Lipid Research Clinics trial in Houston, set up the study with colleagues including the cardiologist Stuart Cobbe. The men took pravastatin 40 mg each evening or placebo, and all received advice on diet and smoking. Average follow-up was 4.9 years, and the primary endpoint was nonfatal myocardial infarction or death from coronary heart disease.

Pravastatin lowered total cholesterol by 20 percent and LDL by 26 percent. There were 174 coronary events against 248 on placebo, a 31 percent reduction, and nonfatal heart attacks alone fell by the same proportion. Death from all cardiovascular causes fell by 32 percent, and deaths from any cause fell by 22 percent, a result just short of conventional significance (P = 0.051).

Published in the New England Journal of Medicine in November 1995, the trial landed in a debate that had been active for years about whether lipid lowering in primary prevention would prove beneficial or might carry hidden risks. A 1990 BMJ review of six earlier primary prevention trials had found no effect on total mortality and more deaths from accidents, suicide and violence in treated men. WOSCOPS found no excess of noncardiovascular deaths.

CARE, published in 1996, showed benefit after myocardial infarction in patients with average cholesterol, and AFCAPS/TexCAPS, published in 1998, extended primary prevention to men and women with average cholesterol. Twenty-year follow-up of the Scottish men through health records, reported in 2016, found 13 percent lower all-cause mortality in those first assigned to pravastatin, mostly from 21 percent fewer cardiovascular deaths, with no difference in cancer deaths.