ADMINISTRATION-TIME-DEPENDENT EFFECTS OF SPIRAPRIL ON AMBULATORY BLOOD PRESSURE IN UNCOMPLICATED ESSENTIAL HYPERTENSION

Jun 8, 2010Chronobiology international

Spirapril’s effects on daily blood pressure vary with time of day in simple high blood pressure

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Abstract

Bedtime administration of spirapril resulted in a 59% increase in the proportion of patients with controlled ambulatory blood pressure.

The study involved 165 previously untreated hypertensive subjects aged 42.5 ± 13.9 years.
Similar reductions in blood pressure during daytime activities were observed for both morning and bedtime dosing.
Bedtime spirapril administration was significantly more effective in reducing blood pressure during sleep compared to morning administration.
A decrease in the awake/asleep blood pressure ratio was noted with morning dosing, while bedtime dosing improved this ratio toward a dipping pattern.
Sleep-time blood pressure regulation was achieved more effectively with bedtime spirapril, which may be linked to the nighttime activation of the renin-angiotensin-aldosterone system.

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The administration of most angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) at bedtime results in a greater reduction of nighttime blood pressure (BP) than dosing upon awakening. It has been proposed that this effect may be a consequence of a short half-life and duration of action. However, those findings were also documented for long-acting medications, such as the ARB telmisartan. Accordingly, we investigated the administration-time-dependent effects on ambulatory BP of spirapril, an ACEI with an elimination half-life of about 40 h. We studied 165 previously untreated hypertensive subjects, 42.5 +/- 13.9 yrs of age, treated with spirapril (6 mg/day) as monotherapy for 12 weeks either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 h before and after treatment. The BP reduction during diurnal activity was similar for both treatment times. Bedtime spirapril administration, however, was significantly more efficient than morning administration in reducing asleep BP. The awake/asleep BP ratio was decreased with the upon-awakening spirapril treatment schedule but significantly increased toward a more dipping pattern with the bedtime treatment schedule. The proportion of patients with controlled ambulatory BP increased from 23 to 59% (p < 0.001) with bedtime treatment. Sleep-time BP regulation is significantly better achieved with bedtime spirapril administration. This might be clinically important, as the sleep-time BP mean has been shown to be a more relevant marker of cardiovascular risk than the awake mean values. These administration-time-dependent effects of spirapril seem to be a class-related feature, and may be associated with the nocturnal activation of the renin-angiotensin-aldosterone system.

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ADMINISTRATION-TIME-DEPENDENT EFFECTS OF SPIRAPRIL ON AMBULATORY BLOOD PRESSURE IN UNCOMPLICATED ESSENTIAL HYPERTENSION

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