High tierRandomized Controlled TrialCitation verified
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Scandinavian Simvastatin Survival Study Group - The Lancet, 1994
The first statin trial to show that lowering cholesterol reduces total mortality, not just cardiovascular events. In coronary patients, simvastatin cut the relative risk of death by 30% over a median 5.4 years, driven by fewer coronary deaths, with non-cardiovascular deaths essentially unchanged.
Key findings
- All-cause mortality: 256 (12%) died on placebo vs 182 (8%) on simvastatin; relative risk of death 0.70 (95% CI 0.58-0.85, p=0.0003).
- Coronary deaths reduced (RR 0.58); non-cardiovascular deaths unchanged (46 vs 49).
- Major coronary events reduced 34% (RR 0.66, 95% CI 0.59-0.75).
Effect measures
- Relative Risk Reduction: 30% lower risk of death (RR 0.70)95% CI 0.58-0.85
- Absolute Risk Reduction: 4 percentage points (12% placebo vs 8% simvastatin)
Why this evidence tier (High)
- Risk of bias:
- Large double-blind randomized placebo-controlled trial; ran to a prespecified end (not stopped early).
- Precision:
- Adequately powered for mortality; tight confidence interval on the death endpoint.
- Directness:
- Measures the hardest endpoint - all-cause mortality - directly in coronary patients.
- Consistency:
- Concordant with later statin trials and meta-analyses.
- Funding / COI:
- Funded by the manufacturer (Merck); a conflicted sponsor, though the hard mortality endpoint and independent replication limit how much that could distort the result.
High certainty that statin therapy reduces all-cause mortality in secondary prevention - the landmark mortality result.
- Population:
- Secondary prevention: 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L; 94 Scandinavian centres; median follow-up 5.4 years.
- Conflicts of interest:
- Industry-sponsored by Merck, which manufactures simvastatin. The 1994 Lancet era predates standardized COI disclosure fields.
- Funding:
- Merck Research Laboratories (manufacturer of simvastatin).
Limitations
- Secondary prevention only; does not speak to low-risk primary prevention.
- Manufacturer-funded, though the endpoint is hard mortality and has been independently replicated.
How this study is used
- Strongly supportsDo statins help people live longer, or only reduce heart events?