Can a long half-life angiotensin II blocker have greater effects on the circadian variation of blood pressure?

Abstract

Clinical trials have shown that small BP elevations increase cardiovascular (CV) risk. Furthermore, 24 hour and early morning BP are strongly linked to target organ damage and cardiovascular events. Thus, ideally antihypertensive drugs should induce both substantial reduction in 24 hour BP and have persistent clinical effects throughout the dosing period. In this study, we evaluated the impact of telmisartan (plasma half-life = 24 hours) versus valsartan (plasma half-life = 6-8 hours) using ambulatory blood pressure monitoring (ABPM) in over 450 patients. This was a prospective, multicenter, double-blind, parallel-group forced-titration trial in which patients were randomized to receive telmisartan (40 to 80 mg once daily) or valsartan (80 to 160 mg once daily) for a total of 8 weeks. Entry criteria included a seated clinic diastolic BP ≥ 95 mm Hg and ≤109 mm Hg and a 24-hour ambulatory DBP ≥ 85 mm Hg. The primary end point was the change from baseline in BP during the last 6 hours of the 24-hour dosing interval. Data were analyzed by analysis of covariance with baseline BP and drug treatment group as covariates. There were 456 patients randomized to either telmisartan or valsartan. The change from baseline in ambulatory diastolic BP during the last 6 hours was −7.7 ± 0.6 mmHg for the telmisartan group (n=231) vs −5.7 ± 0.6 mmHg for the valsartan group (n=225; P =.01. The change from baseline for 24 hour systolic BP was −11.2 ± 0.8 mmHg for telmisartan and −8.8 ± 0.8 mmHg for valsartan (P=.02). There were no differences in adverse events between the 2 groups. These data show that telmisartan, the new angiotensin II receptor blocker with an inherently long plasma half-life had clinically and significantly greater reductions in ambulatory BP during the last 6 hours of the dosing interval than valsartan.