Een wonderlijk resultaat met candesartan

Comments on: Eklind-Cervenka M, Benson L, Dahlstrom U, Edner M, Rosenqvist M, Lund L. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA 2011;305:175-82. In a large observational study in 30,254 patients with heart failure (with and without reduced ejection fraction) from a Swedish registry, the prescription of candesartan vs losartan was associated with a lower mortality risk after correction for confounding by the propensity scores method (HR 0.70, 95% CI 0.61-0.81; p < 0.001). We conclude that this study should not change clinical practice, as several alternative explanations for this result should be considered. Firstly, lower drug adherence in everyday practice as compared with that in RCTs has a greater effect on results with losartan as it has a higher sensitivity to a missed dose than candesartan does. Secondly, 'low' dose losartan was compared to 'high' dose candesartan (non-equipotential dosages). Both of the factors mentioned above could have resulted in insufficient angiotensin receptor blocking by losartan as compared with candesartan, and are related to the inadequate use of losartan. In addition, adjustments for confounding in this observational study cannot be evaluated properly. Finally, there was considerable (selective) loss-to-follow-up, which could also have led to bias. Head-to-head comparisons of drugs should be done with equipotential dosages in an RCT, not in an observational study.