Cilazapril plus hydrochlorothiazide: improved efficacy without reduced safety in mild to moderate hypertension. A double-blind placebo-controlled multicenter study of factorial design.
In this multicenter, placebo-controlled, double-blind, 4 x 3 factorial design study, 1,162 patients randomized into 12 parallel groups received either placebo (n = 97), cilazapril (CLZ 0.5, 5, or 10 mg; n = 288 total), hydrochlorothiazide (HCTZ 12.5 or 25 mg; n = 198 total), or one of the six possible combinations of the two drugs (n = 579 total) given orally once daily for 4 weeks. The mean decrease from baseline in predose (i.e., 24 h postdose) sitting diastolic blood pressure (SDBP) was statistically significantly (p < 0.01) greater for all combinations studied compared to placebo, as well as to their respective monotherapy components. Synergistic antihypertensive effects were noted for the 5/12.5 mg CLZ/HCTZ combination therapy. The normalization (SDBP < or = 90 mm Hg) rate of the 5/12.5 mg CLZ/HCTZ combination was essentially additive with respect to the component monotherapies. The tolerability profile of the CLZ/HCTZ combination was similar to its respective components and comparable to placebo. The CLZ/HCTZ group reported low serum potassium (K+) and high serum uric acid less frequently than the HCTZ group. Therefore, the CLZ/HCTZ combination (5 mg/12.5 mg) is an option for hypertensive patients not responding to single drug CLZ therapy.
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Hoffmann-La Roche, Nutley, N.J. 07110.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D012720:Severity of Illness Index; D014527:Uric Acid / Q000097:blood
D006852:Hydrochlorothiazide; D017315:Cilazapril; D014527:Uric Acid; D011188:Potassium