June 28, 2005Circulation221 citationsOpen Access
View Full PaperEffects of Candesartan on the Development of a New Diagnosis of Diabetes Mellitus in Patients With Heart Failure
Key Result
Candesartan reduced the development of new-onset diabetes compared with placebo in patients with heart failure (6.0% vs 7.4%; HR 0.78; 95% CI 0.64-0.96; P=0.020).
Key Points
- This research aims to determine the effect of candesartan on the development of diabetes in patients with heart failure.
- Randomized, controlled, double-blind trial involving 5436 heart failure patients without diabetes.
- Patients received either candesartan (32 mg daily) or placebo for 2 to 4 years.
- Assessment of diabetes development as a predefined secondary outcome.
- Diabetes developed in 6.0% of the candesartan group compared to 7.4% in the placebo group (HR 0.78, 95% CI 0.64 to 0.96, P=0.020).
- Composite endpoint of death or diabetes occurred in 25.2% of the candesartan group versus 28.6% of the placebo group (HR 0.86, 95% CI 0.78 to 0.95, P=0.004).
- Benefit appeared smaller in patients also treated with ACE inhibitors (HR 0.88, 95% CI 0.65 to 1.20).
Study Design
Type
RCT (n=5,436)
Blinding
double-blind
Randomization
randomized
Structured PICO
Does candesartan prevent the development of a new diagnosis of diabetes mellitus in patients with heart failure without baseline diabetes?
P
Population
5,436 patients with heart failure and no baseline diagnosis of diabetes, followed for 2 to 4 years.
I
Intervention
Candesartan (target of 32 mg once daily) for 2 to 4 years
C
Comparator
Matching placebo
O
Outcome
Development of a new diagnosis of diabetes mellitushard clinical
Candesartan significantly reduces the incidence of new-onset diabetes in patients with heart failure, suggesting a protective effect of angiotensin receptor blockade on glucose regulation.
Main Result
Hazard Ratio: 0.78 (95% CI 0.64–0.96)
Absolute Event Rate: 6% vs 7.4%
p-value: p=0.020
Abstract
BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS: We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio HR, 0.78 with a 95% confidence interval CI of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.