A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL).
BACKGROUND
When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension.


OBJECTIVE
This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated.


METHODS
This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values.


RESULTS
A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%).


CONCLUSIONS
As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.
Coca
Antonio
A
Hospital Clinic, IDIBAPS, University of Barcelona, Spain. acoca@clinic.ub.es
Calvo
Carlos
C
García-Puig
Juan
J
Gil-Extremera
Blas
B
Aguilera
Maria T
MT
de la Sierra
Alejandro
A
Martín-Hidalgo
Alberto
A
Marín
Rafael
R
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D004311:Double-Blind Method; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D013030:Spain; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan