Controlling blood pressure throughout the day: issues in testing a new anti-hypertensive agent.
Lessons learned from ambulatory blood pressure (BP) monitoring strongly influence the development of new anti-hypertensive drugs. Efficacy should be demonstrated not only in the conventional clinical setting, but also throughout the full 24 h day, including the important early morning hours near the end of dosing intervals. Preservation of the circadian pattern, including appropriate day/night BP differences, may be a further important goal of therapy. The reproducibility of ambulatory monitoring measurements, together with the absence of placebo effects with this technique, adds greatly to its power and efficiency. Moreover, the use of ambulatory monitoring to accurately diagnose hypertension and exclude non-confirmed or white coat hypertensives from clinical trials adds further sensitivity to quantifying drug action. This technique was recently applied to the evaluation of the new angiotensin II receptor antagonist losartan. Hypertensive patients diagnosed by ambulatory monitoring were divided into four groups: placebo, losartan 50 mg once daily, 100 mg once daily or 50 mg twice daily. Compared with placebo, which had no effect, all three losartan regimens decreased SBP and DBP significantly. There was no difference in efficacy between the two once daily regimens, although 50 mg twice daily was slightly more effective than 50 mg once daily but not statistically significantly different from 100 mg once daily. However, all losartan groups exhibited sustained BP reductions throughout the 24 h dosing interval and preserved the circadian BP patterns. Ambulatory monitoring was thus able to accurately quantity the efficacy and the key chronobiological aspects of anti-hypertensive therapy with losartan in an efficient and cost-effective manner.
Weber
M A
MA
Hypertension Center (111BP) Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
Neutel
J M
JM
Smith
D H
DH
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan