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Sunday, April 15, 2012

Mortality Risk in Heart Failure No Higher with Losartan


Patients with heart failure who were taking losartan did not have a greater mortality risk than those who were taking candesartan (Atacand), a Danish study showed.
Through 2 to 3 years of follow-up, losartan treatment overall was not associated with either all-cause mortality (HR 1.10, 95% CI 0.96 to 1.25) or cardiovascular mortality (HR 1.14, 95% CI 0.96 to 1.36), according to Henrik Svanström, MSc, of the Statens Serum Institute in Copenhagen, and colleagues.
In secondary analyses, however, patients taking low or medium doses of losartan were more likely to die during follow-up compared with those taking the highest doses of candesartan (HRs 2.79 and 1.39, respectively), the researchers reported in the April 11 issue of the Journal of the American Medical Association.
Patients taking the highest dose of losartan (100 mg) had a mortality risk similar to those taking the highest candesartan doses (HR 0.71, 95% CI 0.50 to 1.00).
"Given these findings, it cannot simply be concluded that any single drug of losartan and candesartan is superior to the other in patients with heart failure, but rather that differential effects may be expected according to the dose achieved," the authors wrote.
"However, given that these findings stem from observational data and that the magnitude of the differences between different doses seems large, an alternative explanation to the differential effects across losartan doses (and across candesartan doses) is the possibility of unmeasured confounding because of frailty (e.g., patients with frailty and advanced heart failure tolerating only low doses of losartan and because of the severity of heart failure being more likely to die than patients who tolerate high candesartan doses)."
Angiotensin II receptor blockers like losartan and candesartan are recommended in patients with heart failure who cannot take ACE inhibitors, and the benefits are believed to be classwide. Observational data, however, suggest that losartan might carry a greater mortality risk than other drugs in the class.
To explore the issue, Svanström and colleagues conducted a cohort study of patients 45 and older with a first-time hospitalization for heart failure from 1998 to 2008. The data came from multiple Danish national registries.
The analysis included 4,397 new users of losartan and 2,082 new users of candesartan. Mean age was about 72.
For losartan users, there were 1,212 deaths during a median of 2.7 years of follow-up (10.7 per 100 person-years), and for candesartan users, there were 330 deaths during a median of 1.9 years of follow-up (9.0 per 100 person-years).
Patients using losartan were older, more likely to have had an MI, unstable angina, and chronic pulmonary disease, and to have been hospitalized within the last year, and less likely to have had a stroke.
After accounting for these differences using propensity score adjustment, there was no difference in mortality between users of losartan and candesartan overall.
That finding conflicts with the results of an analysis based on a Swedish heart failure registry published last year.
That study showed that patients taking candesartan had a lower mortality rate than those taking losartan at both 1 and 5 years of follow-up.
Possible explanations for the discrepancy, according to Svanström and colleagues, include the use of a wider range of potential confounders to better account for baseline differences between the two groups in the current study and differences in the likelihood of achieving target doses with each drug.
The researchers acknowledged some limitations of the current study, including the lack of measures of heart failure severity such as left ventricular ejection fraction, the inability to determine whether patients were compliant with therapy, the lack of information on prescribed drug dose, possible residual confounding, and the uncertain generalizability to patients with heart failure earlier in the course of the disease.
The study was supported by grants from the Danish Medical Research Council.
The authors reported that they had no conflicts of interest.

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