High tierRandomized Controlled TrialCitation verified
Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
Peter S Sever, Bjorn Dahlof, Neil R Poulter, Hans Wedel, ASCOT Investigators - The Lancet, 2003
A primary-prevention trial in hypertensive patients with average or below-average cholesterol. Atorvastatin cut the primary endpoint of nonfatal MI plus fatal CHD by 36% (HR 0.64), prompting early termination. Stroke fell too, but all-cause mortality was not significantly reduced - a pattern typical of shorter primary-prevention trials.
Key findings
- Primary endpoint (nonfatal MI + fatal CHD): 100 vs 154 events; HR 0.64 (95% CI 0.50-0.83, p=0.0005).
- Fatal and nonfatal stroke: HR 0.73 (95% CI 0.56-0.96).
- All-cause mortality: HR 0.87 (95% CI 0.71-1.06, p=0.16) - not significant.
Effect measures
- Hazard Ratio: 0.64 (primary endpoint)95% CI 0.50-0.83
- Hazard Ratio: 0.87 (all-cause mortality, not significant)95% CI 0.71-1.06
Why this evidence tier (High)
- Risk of bias:
- Large randomized controlled trial, but stopped early for benefit, which tends to overestimate the effect.
- Precision:
- Adequate for the composite endpoint; underpowered for mortality over its short follow-up.
- Directness:
- Hard clinical endpoints in hypertensive primary prevention with average cholesterol.
- Consistency:
- Concordant with other primary-prevention statin trials.
- Funding / COI:
- Manufacturer-funded (Pfizer); a conflicted sponsor.
High certainty for event reduction in hypertensive primary prevention; early stopping and short follow-up mean the absolute and mortality picture is less settled.
- Population:
- Hypertensive patients aged 40-79 with total cholesterol <=6.5 mmol/L (average or below) and at least three other cardiovascular risk factors; primary prevention (no prior CHD). Stopped early after median 3.3 years.
- Conflicts of interest:
- Industry-funded by Pfizer, which manufactures atorvastatin. Funding detail is in the Lancet full text, not the PubMed abstract.
- Funding:
- Pfizer (manufacturer of atorvastatin), with support from Servier and Leo Laboratories.
Limitations
- Stopped early for benefit - the effect size is likely somewhat inflated.
- Short median follow-up (3.3 years); no significant mortality benefit.
- Hypertensive, multi-risk-factor population - not low-risk.