P. Asmar et Y. Lacourciere, A new approach to assessing antihypertensive therapy: effect of treatment on pulse pressure, J HYPERTENS, 18(11), 2000, pp. 1683-1690
Citations number
33
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background A high pulse pressure is an independent cardiovascular risk fact
or. 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 previo
us analysis, we showed that two angiotensin II type 1 (AT(1))-receptor bloc
kers, candesartan cilexetil and losartan, differed in their effects in redu
cing SBP and DBP.
Objective To compare the efficacy of candesartan cilexetil and losartan acc
ording 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.
Methods After a 4-week placebo run-in period, 268 patients with mild-to-mod
erate hypertension were allocated randomly to groups to receive placebo, ca
ndesartan 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 moni
tored from 0 to 36 h after each dose, at baseline and after 4 and 8 weeks o
f treatment. Results Candesartan cilexetil decreased ambulatory pulse press
ure 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 d
uration of action of candesartan cilexetil was greater than that of losarta
n. 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 wi
th candesartan cilexetil were lower than those observed with losartan (P <
0.005). Clinic pulse pressure measurements were consistent with these ambul
atory measurements.
Conclusions AT(1) -receptor blockers differ both in their ability to reduce
pulse pressure and in their duration of effect, candesartan cilexetil havi
ng a greater and more sustained effect than losartan. Different dose-effect
relationships on SBP, DBP or pulse pressure were observed. Further prospec
tive studies based on pulse pressure are needed to analyse the mechanism of
reduction of pulse pressure end to determine its prognostic value. J Hyper
tens 18:1683-1690 (C) 2000 Lippincott Williams & Wilkins.