Association of Treatment With Losartan vs Candesartan and Mortality Among Patients With Heart Failure

Study Questions:

Is there a mortality difference in patients with heart failure (HF) treated with losartan versus candesartan?


This was a nonrandomized, nonblinded analysis of patients ≥45 years of age enrolled into a nationwide Danish registry between 1998-2008. Selected patients had an incident HF hospitalization and were new users of losartan or candesartan (no prescription record for either drug within 3 years of enrollment). The primary outcome of interest was all-cause mortality based on angiotensin-receptor blocker (ARB) type.


Of the 6,479 patients in the cohort, 2,082 (32%) were on candesartan and 4,397 were on losartan. Patients on losartan had longer treatment (1.8 years [interquartile range 0.5-4.1]) and follow-up (2.7 [1.1-5.1]) than candesartan patients (1.1 years [0.4-2.5] and 1.9 years [0.8-3.4], respectively) and tended to be older (72.7 vs. 71.7 years, respectively, p < 0.001). While the unadjusted risk of death (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.1-1.4) was higher with losartan use, mortality was not significantly different after propensity score adjustment (HR, 1.1; 95% CI, 0.96-1.3) or multivariable modeling (HR, 1.08; 95% CI, 0.95-1.22). Mortality was also not different in patients on high-dose losartan versus high-dose candesartan (HR for losartan, 0.71; 95% confidence interval, 0.50-1.0).


The authors concluded that in patients with HF, there was no significant mortality difference between candesartan and losartan.


The authors investigated if the impact of ARB therapy on HF mortality was due to a class effect, citing prior studies suggesting increased mortality in HF patients treated with losartan. While significant differences were not noted, magnitudes of increased risk were similar and trending toward significance in both the propensity score adjusted and multivariable analyses. The patients on losartan contributed more overall data with longer duration of therapy and follow-up. However, I am not convinced that this is a ‘negative’ study based on the data presented, albeit risk increments appear to be <10%.

Clinical Topics: Heart Failure and Cardiomyopathies, Novel Agents, Acute Heart Failure

Keywords: Losartan, Propensity Score, Proto-Oncogene Proteins, Benzimidazoles, Heart Failure, Confidence Intervals, Tetrazoles, Receptors, G-Protein-Coupled, Hospitalization

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