High tierRandomized Controlled TrialCitation verified
Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease
Salim Yusuf, Jackie Bosch, Gilles R Dagenais, Jun Zhu, HOPE-3 Investigators - New England Journal of Medicine, 2016
The cleanest test of statins in ordinary primary prevention: it enrolled intermediate-risk people without selecting them by cholesterol level. Rosuvastatin lowered LDL by 26.5% and reduced the first coprimary endpoint by 24% (HR 0.76), with an absolute event reduction of roughly 1.1 points over 5.6 years and no excess of diabetes or cancer.
Key findings
- First coprimary outcome (CV death, nonfatal MI, nonfatal stroke): 3.7% vs 4.8%; HR 0.76 (95% CI 0.64-0.91, p=0.002).
- LDL cholesterol lowered 26.5% vs placebo.
- No excess of diabetes or cancer; small excess of cataract surgery and muscle symptoms.
Effect measures
- Hazard Ratio: 0.76 (first coprimary outcome)95% CI 0.64-0.91
- Absolute Risk Reduction: ~1.1 percentage points (3.7% vs 4.8%)
- Number Needed To Treat: ~91 over 5.6 years (derived from the 1.1-point absolute reduction; not stated in the abstract)
Why this evidence tier (High)
- Risk of bias:
- Large double-blind randomized placebo-controlled trial run to completion.
- Precision:
- Well powered; precise estimate around a modest absolute effect.
- Directness:
- The most directly relevant trial for unselected intermediate-risk primary prevention - no lipid-based entry criterion.
- Consistency:
- Concordant with the broader statin evidence.
- Funding / COI:
- Co-funded by AstraZeneca alongside a public funder (CIHR); partial industry sponsorship.
High certainty that statins reduce events in unselected intermediate-risk primary prevention; the honest qualifier is that the absolute benefit is modest.
- Population:
- 12,705 intermediate-risk adults in 21 countries without cardiovascular disease, enrolled WITHOUT lipid-level selection (rosuvastatin 10 mg vs placebo arm); median follow-up 5.6 years.
- Conflicts of interest:
- Partly industry-funded (AstraZeneca, co-sponsor with CIHR). The drug manufacturer is explicitly named in the funding statement.
- Funding:
- Canadian Institutes of Health Research and AstraZeneca (manufacturer of rosuvastatin); NCT00468923.
Limitations
- Intermediate-risk, not the very lowest-risk; absolute benefit is modest.
- Industry co-sponsorship by the drug manufacturer.