Effects of Candesartan cilexetil in patients with severe systemic hypertension

The efficacy, tolerability, and safety of the potent angiotensin II recepto r blocker candesartan cilexetil were evaluated in 217 adult patients (68% m en, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-bl ind, placebo-controlled study. Patients with sifting diastolic blood pressu re (BP) greater than or equal to 110 mm Hg during the placebo run-in receiv ed HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan ci lexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. A fter 1 week of double-blind treatment, patients with sifting diastolic BP g reater than or equal to 90 mm Hg were uptitrated to candesartan cilexetil 1 6 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitr ation. Primary efficacy measurement was a change in trough (24 +/- 3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to do uble-blind week 4. Mean changes in systolic and diastolic BP were significa ntly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <00.01/p <0.001, respectively. Patients with hig her sitting diastolic BP at the end of the HCTZ run-in tended to have great er decreases in BP (p <0.05). Most patients (53%) receiving candesartan cil exetil were responders (diastolic BP <90 mm Hg or greater than or equal to 10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolera bility and safety profiles were similar in the candesartan and placebo grou ps. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effec tive and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in th e United States. (C) 1999 by Excerpta Medica, Inc.