High tierRandomized Controlled TrialCitation verified
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
J Shepherd, S M Cobbe, I Ford, C G Isles, A R Lorimer, West of Scotland Coronary Prevention Study Group - New England Journal of Medicine, 1995
The first large primary-prevention statin trial. In hypercholesterolaemic men with no prior heart attack, pravastatin lowered LDL by 26% and cut the combined risk of nonfatal MI or coronary death by 31%. All-cause mortality fell 22%, but that result was borderline and not statistically significant (p=0.051).
Key findings
- Combined nonfatal MI or coronary death reduced 31% (248 vs 174 events; 95% CI 17-43%, p<0.001).
- All-cause mortality reduced 22% but borderline non-significant (95% CI 0-40%, p=0.051).
- LDL cholesterol lowered 26%; total cholesterol 20%.
Effect measures
- Relative Risk Reduction: 31% fewer nonfatal MI / coronary deaths95% CI 17-43%
- Relative Risk Reduction: 22% lower all-cause mortality (borderline, p=0.051)95% CI 0-40%
Why this evidence tier (High)
- Risk of bias:
- Large double-blind randomized placebo-controlled primary-prevention trial.
- Precision:
- Well powered for the composite endpoint; the mortality endpoint was underpowered (borderline).
- Directness:
- Hard clinical endpoints in a true primary-prevention population.
- Consistency:
- Concordant with later primary-prevention trials and meta-analyses.
- Funding / COI:
- Manufacturer-funded (Bristol-Myers Squibb); a conflicted sponsor.
High certainty for event reduction in higher-risk (hypercholesterolaemic) primary prevention; the mortality signal alone is only borderline.
- Population:
- 6595 men aged 45-64 with hypercholesterolaemia (mean cholesterol ~7.0 mmol/L) and no history of myocardial infarction; average follow-up 4.9 years.
- Conflicts of interest:
- Industry-sponsored by Bristol-Myers Squibb, which manufactures pravastatin. Funding statement is in the NEJM full text, not the PubMed abstract.
- Funding:
- Bristol-Myers Squibb Pharmaceutical Research Institute (manufacturer of pravastatin).
Limitations
- Population was selected for high cholesterol, so it is not "low-risk" primary prevention.
- Men only; results may not transfer directly to women.
- All-cause mortality benefit did not reach significance.