The relationships between dose and antihypertensive effect of four AT1-receptor blockers.: Differences in potency and efficacy

The relationships between dose and antihypertensive effect of the first four available AT(1)-receptor blockers, i.e. losartan, valsartan, irbesartan and candesartan, were assessed based on data obtained from the FDA's evaluation reports of the respective New Drug Application files. All available randomized, double-blind, placebo-controlled, parallel-group studies in adult men and women with mild to moderate primary diastolic hypertension were included, provided that the reduction in trough (24 h post-dose) supine or sitting diastolic blood pressure (DBP) had been assessed using the intention-to-treat approach. All studies had an initial single-blind placebo run-in period followed by at least 4 weeks double-blind treatment. The selected studies were included in a meta-analysis of the dose-response relationship for each drug. The dose-response relationship was estimated by fitting the placebo-adjusted, weighted mean reductions in DBP for each dose of the drug to an E-max model. The E-max (maximal effect at an infinitely large dose) for the reduction in DBP, with corresponding 95% confidence intervals in brackets, were found to be 5.6 (3.6-7.5) mmHg for losartan, 5.8 (5.0-6.6) mmHg for valsartan, 6.9 (5.9-7.9) mmHg for irbesartan and 7.5 (6.1-8.9) mmHg for candesartan (p = 0.014, candesartan vs valsartan). In conclusion, this investigation demonstrates that candesartan can reduce DBP significantly more than valsartan, and is supportive of previous head-to-head comparisons, which have proven candesartan to have a greater antihypertensive effect than losartan at recommended doses. Thus, differences in efficacy between different AT(1)-receptor blockers do exist, and should have implications for the choice of AT(1)-receptor blocker when treating patients with hypertension, considering the importance of good blood pressure control.