Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone

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Abstract
The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP ≤ 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan–hydrochlorothiazide or the valsartan–benazepril combination. The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (−4.5 during valsartan–hydrochlorothiazide treatment and −3.3 mmHg during valsartan–benazepril treatment), but of greater magnitude for systolic BP during valsartan–hydrochlorothiazide (−6.77 mmHg) than during valsartan–benazepril co-administration (−3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.