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Abstract

Antihypertensive agents may differ in their efficacy during the early-morning period, a time of increased cardiovascular risk. To examine the impact of a chronotherapeutic calcium antagonist versus conventional morning administration of drugs that block the renin-angiotensin system, we studied the effects of COER-verapamil, enalapril, and losartan on the blood pressure (BP) and the heart rate-systolic BP product (RPP) during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. The 357 men and women enrolled had an untreated seated diastolic BP of 95-109 mm Hg and an ambulatory daytime diastolic BP ≥85 mm Hg. Patients were randomized to either COER-verapamil each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg) or placebo. Assessments of BP and RPP were performed using 24-hour ambulatory recordings following 4 weeks (low dose) and 8 weeks (high dose) of therapy. Following 8 weeks of treatment, reductions in early-morning BP by COER-verapamil were significantly greater compared to enalapril and losartan. COER-verapamil also induced a greater reduction in early-morning RPP compared with losartan, and greater reductions in the rate of rise of BP compared to both enalapril and losartan (Table).

ParameterPlaceboCOER-VerEnalaprilLosartan
N4610999103
ΔAM BP-1/0 ± 10/7-15/-10 ± 13/11*-9/-7 ± 13/8-8/-5 ± 11/8
ΔAM RPP-150±1619-1537±1993⊥-1106±1290-680±1553
ΔAM Rate of Rise BP-0.1/-0.2-2.6/-1.5**0/-0.10.4/0.2
ParameterPlaceboCOER-VerEnalaprilLosartan
N4610999103
ΔAM BP-1/0 ± 10/7-15/-10 ± 13/11*-9/-7 ± 13/8-8/-5 ± 11/8
ΔAM RPP-150±1619-1537±1993⊥-1106±1290-680±1553
ΔAM Rate of Rise BP-0.1/-0.2-2.6/-1.5**0/-0.10.4/0.2

COER-Ver=COER-verapamil

*

P<0.01 vs enalapril and losartan;

**

P<0.01 vs losartan,P<0.05 vs enalapril;

⊥

P<0.05 vs losartan;

ParameterPlaceboCOER-VerEnalaprilLosartan
N4610999103
ΔAM BP-1/0 ± 10/7-15/-10 ± 13/11*-9/-7 ± 13/8-8/-5 ± 11/8
ΔAM RPP-150±1619-1537±1993⊥-1106±1290-680±1553
ΔAM Rate of Rise BP-0.1/-0.2-2.6/-1.5**0/-0.10.4/0.2
ParameterPlaceboCOER-VerEnalaprilLosartan
N4610999103
ΔAM BP-1/0 ± 10/7-15/-10 ± 13/11*-9/-7 ± 13/8-8/-5 ± 11/8
ΔAM RPP-150±1619-1537±1993⊥-1106±1290-680±1553
ΔAM Rate of Rise BP-0.1/-0.2-2.6/-1.5**0/-0.10.4/0.2

COER-Ver=COER-verapamil

*

P<0.01 vs enalapril and losartan;

**

P<0.01 vs losartan,P<0.05 vs enalapril;

⊥

P<0.05 vs losartan;

The 24-hour BP treatment effect of COER-verapamil was equivalent to enalapril and superior to losartan. The results at 4 weeks were similar to 8 weeks. Thus, nocturnal administration of an agent designed to parallel the circadian rhythm of BP and HR had significantly greater early-morning hemodynamic effects compared to conventional once-daily agents.

Early Am Blood Pressure Surge, Chronobiology, Antihypertensive Therapy
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© American Journal of Hypertension, Ltd. 2001
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