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- Title
Combination candesartan-HCTZ did not reduce major CV events in patients at intermediate CV risk.
- Authors
Eaton MD, Charles B.
- Abstract
Question In patients at intermediate cardiovascular (CV) risk, does combination candesartan-hydrochlorothiazide (HCTZ) reduce major CV events? Methods Design Randomized, placebo-controlled trial (Heart Outcomes Prevention Evaluation [HOPE]-3 trial). ClinicalTrials.gov NCT00468923. Allocation Concealed.* Blinding Blinded* (patients, clinicians, outcome assessors, and steering committee). Follow-up period Median 5.6 years. Setting 228 clinical centers in 21 countries on 6 continents. Patients 12705 men ≥55 years of age and women ≥65 years of age who had ≥1 CV risk factor (elevated waist-to-hip ratio, dysglycemia, mild renal dysfunction, recent or current use of tobacco, previous low high-density lipoprotein cholesterol level, and family history of premature coronary disease) or were ≥60 years of age with ≥2 risk factors; and adhered to a 4-week run-in phase with blood pressure and cholesterol treatments and had no unacceptable adverse events. Exclusion criteria included CV disease; symptomatic hypotension; moderate or advanced renal dysfunction; or indications for, or contraindications to, study drugs or angiotensin-converting enzyme inhibitors. Mean age of participants was 66 y, and 54% were men. Intervention Fixed-dose combination candesartan-HCTZ, 16 mg/d-2.5 mg/d (n=6356), or placebo (n=6349). All patients were also randomized to rosuvastatin or placebo in a 2 x 2 factorial manner. Outcomes Coprimary outcomes were a composite of major CV events (CV death, nonfatal myocardial infarction [MI], or nonfatal stroke) and a composite of major CV events, resuscitated cardiac arrest, heart failure, or revascularization. Secondary outcomes included fatal or nonfatal stroke and adverse events. The trial had 80% power to detect a ≥22.5% relative reduction in the first (α =0.04) and second (α =0.02) coprimary outcomes c ompared with placebo. Patient follow-up 99% for primary outcome (intention-to-treat analysis). Main results The main results are in the Table. Groups did not differ for any component of the coprimary composite outcomes, cancer, myopathy, rhabdomyolysis, or hospitalizations (all P≥0.10). Patients who received candesartan-HCTZ were more likely to permanently discontinue study drug due to dizziness, lightheadedness, or hypotension (P>0.001). Conclusion In patients at intermediate cardiovascular risk, combination candesartan-hydrochlorothiazide did not reduce major cardiovascular events.
- Subjects
CARDIOVASCULAR disease prevention; ANTIHYPERTENSIVE agents; DIURETICS; CARDIOVASCULAR diseases risk factors; CONFIDENCE intervals; STATISTICAL correlation; CARDIOPULMONARY resuscitation; LONGITUDINAL method; MEDICAL cooperation; MYOCARDIAL revascularization; PROBABILITY theory; RESEARCH; STROKE; RANDOMIZED controlled trials; RELATIVE medical risk; DESCRIPTIVE statistics; ROSUVASTATIN; THERAPEUTICS
- Publication
ACP Journal Club, 2016, Vol 165, Issue 2, p6
- ISSN
1056-8751
- Publication type
Article
- DOI
10.7326/ACPJC-2016-165-2-007