“There was a decreasing risk of mortality with increasing losartan dose; and no significantly increased mortality risk was observed when comparing the highest dose of losartan against the highest doses of candesartan,” the authors found. “
Henrik Svanstrom and colleagues with the Statens Serum Institut, Copenhagen, point out that different angiotensin II-receptor blockers (ARBs) are used interchangeably in heart failure. However, there is observational evidence indicating that losartan may be associated with increased mortality in this setting compared with other ARBs.
“In particular, a recent cohort study found that use of losartan, as compared with candesartan, was associated with an increased risk of all-cause mortality,” they explain. “However, a considerably smaller proportion of losartan users received the full-target dose compared with candesartan users, which may have favored an apparent superiority of candesartan.”
To look into this issue, the team conducted a study using the Danish National Patient Registry to identify 120,871 patients hospitalized for the first time for heart failure over a 10 year period. In this cohort, 6479 patients initiated treatment during the study period with candesartan (n=2082) or losartan (n=4397).
There were 9.0 deaths per 100 person-years among candesartan users and 10.7 per 100 person-years among losartan users, the investigators found. This translated to an unadjusted all-cause mortality hazard ratio of 1.25 among losartan users compared to candesartan users. However, after adjustment for propensity score, the hazard ratio became insignificant at 1.10.
As mentioned, dosing levels affected the mortality risk. Compared with high-dose candesartan (16-32 mg), the adjusted mortality hazard ratio was significantly higher with low-dose (12.5 mg) losartan (HR 2.79) and with medium-dose (50 mg) losartan (HR 1.39) but not with high-dose (100 mg) losartan (HR 0.71), the authors report.
They conclude, “These findings do not support the hypothesis of differential effects of specific ARBs in patients with heart failure.”
On the other hand, they comment, “Differential effects may be expected according to the dose achieved.”