Cardiology · 1995
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 controlled trial outcome data to cite.
The West of Scotland Coronary Prevention Study recruited 6,595 men from general practices in Glasgow, selecting for a mean LDL of 5.0 mmol/L and excluding anyone with prior myocardial infarction. James Shepherd at the University of Glasgow led the trial alongside co-principal investigator Stuart Cobbe. Participants received pravastatin 40 mg daily or placebo for a median of 4.9 years, with the primary endpoint being nonfatal myocardial infarction or coronary death.
Pravastatin reduced LDL by approximately 26 percent and cut the primary endpoint by 31 percent. All-cause mortality fell by 22 percent, with no excess in non-cardiovascular deaths, addressing a concern from earlier cholesterol-lowering trials using non-statin agents that had shown increased non-cardiac mortality in some analyses. The relative risk reduction was consistent with the dose-response relationship between LDL lowering and event reduction seen in secondary prevention studies.
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. The WOSCOPS data were sufficiently large and the results sufficiently consistent that they substantially settled that debate for high-risk primary prevention. Regulatory agencies and guideline committees incorporated the findings into expanded indications for statins within months of publication.
CARE, published in 1996 in patients with prior MI and average cholesterol, and AFCAPS/TexCAPS, published in 1998 in primary prevention patients with average LDL and below-average HDL, extended the statin primary prevention evidence base. Taken together, the three trials shifted prescribing from a population defined by prior events to one defined by calculated risk. WOSCOPS was the first data point in that shift.
Key People
- James Shepherd — Glasgow lipidologist and principal investigator of WOSCOPS
- Stuart Cobbe — Co-principal investigator, University of Glasgow cardiologist
- Chris Packard — Glasgow biochemist responsible for lipid analysis in the trial
N Engl J Med. 1995;333(20):1301-1307.
Related landmarks
- 1994 · 4S (Scandinavian Simvastatin Survival Study) (Cardiology)
- 1994 · Antiplatelet Trialists' Collaboration Overview (Cardiology)
- 1991 · SOLVD Treatment Trial (Cardiology)
- 2000 · HOPE (Heart Outcomes Prevention Evaluation) (Cardiology)