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 AT1-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 Emax model. The Emax (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 AT1-receptor blockers do exist, and should have implications for the choice of AT1-receptor blocker when treating patients with hypertension, considering the importance of good blood pressure control.
Elmfeldt
Dag
D
Clinical Science, AstraZeneca R&D, Mölndal, Sweden. dag.elmfeldt@astrazeneca.com
Olofsson
Bertil
B
Meredith
Peter
P
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D000077405:Irbesartan; D019808:Losartan; C081643:candesartan