Candesartan a Better Treatment for Patients with Heart Failure

In a head-to-head study, researchers found that compared with losartan, candesartan is associated with lower all-cause mortality in patients with heart failure (HF). In a study presented in the Journal of the American Medical Association [2011;305(2):175-182], researchers examined the 1- and 5-year survival rates for the 2 treatments for patients with HF with reduced left ventricular ejection fraction (LVEF). This is the first study to compare angiotensin II receptor blockers (ARBs) one-on-one. Researchers used the Swedish Heart Failure Registry to locate patients for this study. A total of 5139 patients were involved in the study, with 2639 treated with candesartan and 2500 treated with losartan. The mean age was 74 years, and 39% of the patients were women. Patients’ survival was charted using the Kaplan-Meier method and compared with the log rank test for all patients and separately for an LVEF of <40% and >40%. The results of the study show that the 1-year survival rate for patients receiving candesartan was 90% (95% confidence interval [CI], 89%-91%) and 83% for patients receiving losartan (95% CI, 81%-84%). The 5-year survival rate for patients receiving candesartan was 61% (95% CI, 54%-68%) and 44% for patients receiving losartan treatment (95% CI, 41%-48%; log rank P<.001). The hazard ratio for mortality with losartan compared with candesartan was 1.43 (95% CI, 1.23-1.65; P<.001). In the study, target doses were considered 32 mg/day for candesartan and 50 mg/day for losartan. The study showed that patients receiving candesartan were healthier overall but had lower LVEF and were less likely to reach target doses. Patients with an LVEF of ≥40% were older, more commonly women, and had more atrial fibrillation, but were otherwise healthier than patients with an LVEF of <40%. For patients with an LVEF of <40%, the 1-year survival rate for candesartan and losartan was 91% (95% CI, 89%-92%) and 82% (95% CI, 80%-85%), respectively. The 5-year survival rate for patients with an LVEF of <40% was 68% (95% CI, 60%-76%) and 44% (95% CI, 40%-49%), respectively (P<.001). For patients with an LVEF of ≥40%, the 1-year survival rate for candesartan and losartan was 91% (95% CI, 89%-93%) and 86% (95% CI, 83%-88%), respectively. The 5-year survival rate for patients with an LVEF of ≥40% was 54% (95% CI, 40%-72%) and 50% (95% CI, 44%-56%), respectively (P<.001). The authors of this study found that the difference between the candesartan and losartan treatments was significant even after adjustment for propensity scores and other clinical variables, including dose, potential interactions, and after stratification and quantification of potential residual confounding of a reasonable magnitude. The authors state that this study provides information useful for everyday clinical care of a broad unselected HF population, and the findings are widely applicable. The survival of the patients in the overall population of the study was high, with 54.5% being registered as outpatients. The authors state that inpatient versus outpatient registration did not affect the differences between losartan versus candesartan in this study. Noted limitations of this study include its nonrandomized character and the potential biases and confounders that may be responsible for the findings. The choice of ARB agents may be subject to selection bias, and the authors of the study cannot determine whether hypertension or HF or diabetes were the primary indication. Also, variables beyond the independent ARB agent may affect the findings, such as age, LVEF, renal function, dose of ARB, and treatment with other HF drugs. Overall, the researchers found that the candesartan treatment was associated with a lower mortality risk when compared with the losartan treatment. The authors suggest that future research on this issue should test more ARB agents against one another in a broader registry.