A new approach to assessing antihypertensive therapy

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Abstract
A high pulse pressure is an independent cardiovascular risk factor. It has therefore been suggested that antihypertensive treatment should not only reduce systolic blood pressure (SBP) and diastolic blood pressure (DBP), but should also decrease pulse pressure (SBP minus DBP). In a previous analysis, we showed that two angiotensin II type 1 (AT1)-receptor blockers, candesartan cilexetil and losartan, differed in their effects in reducing SBP and DBP. To compare the efficacy of candesartan cilexetil and losartan according to a new approach—their effect on pulse pressure–and to describe the dose—effect relationship for SBP, DBP and pulse pressure, in a placebo-controlled study. After a 4-week placebo run-in period, 268 patients with mild-to-moderate hypertension were allocated randomly to groups to receive placebo, candesartan cilexetil (8 mg once daily) or losartan (50 mg once daily), for 4 weeks. The doses were then doubled to 16 and 100 mg, respectively, for the final 4 weeks of the study. Clinic blood pressure was measured 24 and 48 h after each dose of drug or placebo, and ambulatory blood pressure was monitored from 0 to 36 h after each dose, at baseline and after 4 and 8 weeks of treatment. Candesartan cilexetil decreased ambulatory pulse pressure significantly (P < 0.05) more than did losartan during both daytime and night-time, and over the 24 h period after the previous dose. A different dose—effect relationship on SBP, DBP and pulse pressure was observed. The duration of action of candesartan cilexetil was greater than that of losartan. After a missed dose (i.e. approximately 24–36 h after the previous dose), mean ambulatory pulse pressure values after 4 and 8 weeks of treatment with candesartan cilexetil were lower than those observed with losartan (P < 0.005). Clinic pulse pressure measurements were consistent with these ambulatory measurements. AT1-receptor blockers differ both in their ability to reduce pulse pressure and in their duration of effect, candesartan cilexetil having a greater and more sustained effect than losartan. Different dose—effect relationships on SBP, DBP or pulse pressure were observed. Further prospective studies based on pulse pressure are needed to analyse the mechanism of reduction of pulse pressure and to determine its prognostic value.