CONTROLLING BLOOD-PRESSURE THROUGHOUT THE DAY - ISSUES IN TESTING A NEW ANTIHYPERTENSIVE AGENT

Lessons learned from ambulatory blood pressure (BP) monitoring strongl y influence the development of new anti-hypertensive drugs. Efficacy s hould be demonstrated not only in the conventional clinical setting, b ut also throughout the full 24 h day, including the important early mo rning hours near the end of dosing intervals. Preservation of the circ adian 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. Moreov er, the use of ambulatory monitoring to accurately diagnose hypertensi on and exclude non-confirmed or white coat hypertensives from clinical trials adds further sensitivity to quantifying drug action. This tech nique was recently applied to the evaluation of the new angiotensin II receptor antagonist losartan. Hypertensive patients diagnosed by ambu latory monitoring were divided into four groups: placebo, losartan 50 mg once daily, 100 mg once daily or 50 mg twice daily. Compared with p lacebo, which had no effect, all three losartan regimens decreased SEP and DBP significantly. There was no difference in efficacy between th e two once daily regimens, although 50 mg twice daily was slightly mor e effective than 50 mg once daily but not statistically significantly different from 100 mg once daily. However, all losartan groups exhibit ed sustained BP reductions throughout the 24 h dosing interval and pre served the circadian BP patterns. Ambulatory monitoring was thus able to accurately quantify the efficacy and the key chronobiological aspec ts of anti-hypertensive therapy with losartan in an efficient and cost -effective manner.