Ambulatory blood pressure-lowering effects of valsartan and enalapril after a missed dose in previously untreated patients with hypertension: a prospective, randomized, open-label, blinded end-point trial

Abstract

Background: Approximately 3 days a month, some 15% to 20% of patients with hypertension do not recall having taken their antihypertensive medication. Individuals with this frequency of missed doses may be at increased risk for a cardiovascular event and may have a poorer long-term prognosis.

Objective: This study used ambulatory blood pressure monitoring (ABPM) to compare the blood pressure (BP)-lowering effects of valsartan and enalapril over the 24 hours after missing 1 dose in previously untreated patients with mild to moderate essential hypertension.

Methods: This was a prospective, randomized, open-label, parallel-group, blinded end-point trial in previously untreated patients (age >18 years) with mild to moderate essential hypertension (European Society of Hypertension-European Society of Cardiology guidelines: systolic BP 140-179 mm Hg or diastolic BP 90-109 mm Hg). Patients were randomly assigned to receive 16 weeks of treatment with valsartan 160 mg/d or enalapril 20 mg/d, taken on waking. ABPM was conducted for 48 consecutive hours at baseline and again after 16 weeks of therapy. Patients took a dose of their assigned treatment at the beginning of the final session of ABPM and were instructed to skip the next daily dose.

Results: The study enrolled 148 Spanish patients (84 men, 64 women; mean [SD] age, 45.8 [10.7] years) with previously untreated hypertension. At the end of treatment, there were significant differences between groups during the first 24 hours of ABPM, starting in the final 6 hours of the dosing interval (P < 0.001). There was no significant change in BP reduction between the first and second 24-hour periods of ABPM with valsartan (-2.1/-1.4 mm Hg), whereas enalapril was associated with a significant increase in BP over this period (5.5/3.8 mm Hg; P < 0.001 vs first 24 hours; P = 0.032 vs valsartan).

Conclusions: In this study in previously untreated patients with mild to moderate essential hypertension, valsartan was associated with a sustained BP-lowering effect beyond the initial 24 hours after dosing, whereas enalapril was not. There was no significant change in the efficacy of valsartan in the 24 hours after a missed dose. At the doses tested, valsartan was more effective than enalapril, both during active treatment and after a missed dose.

Trial registration: ClinicalTrials.gov NCT00302705.