- Question
- Does blood-pressure lowering with candesartan plus hydrochlorothiazide reduce major cardiovascular events in intermediate-risk persons without prior cardiovascular disease?
- Design
- One comparison from a randomized, placebo-controlled 2-by-2 factorial trial with quadruple masking, enrolling 12705 participants. Median follow-up was 5.6 years.
- Population
- Intermediate-risk persons without cardiovascular disease, with a mean baseline blood pressure of 138.1/81.9 mm Hg.
- Intervention
- Candesartan 16 mg per day plus hydrochlorothiazide 12.5 mg per day.
- Control
- Placebo.
- Primary outcome
- First coprimary outcome: composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Second coprimary outcome: the same plus resuscitated cardiac arrest, heart failure, and revascularization.
- Results
- Blood pressure fell 6.0/3.0 mm Hg more with active treatment than with placebo. The first coprimary outcome occurred in 260 participants (4.1%) with active treatment and 279 (4.4%) with placebo (HR 0.93; 95% CI 0.79 to 1.10; P=0.40); the second occurred in 312 (4.9%) and 328 (5.2%), respectively (HR 0.95; 95% CI 0.81 to 1.11; P=0.51). In the upper third of systolic blood pressure (>143.5 mm Hg), active treatment was associated with fewer events, with neutral effects in the middle and lower thirds.
- Conclusion
- Candesartan plus hydrochlorothiazide was not associated with a lower rate of major cardiovascular events than placebo in intermediate-risk persons without cardiovascular disease.
- Why it matters
- The trial questioned the benefit of drug-based blood-pressure lowering in intermediate-risk persons with relatively low blood pressure, and suggested that any benefit is concentrated in those with higher blood-pressure levels.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026