Efficacy and safety of various combination therapies based on a calcium antagonist in essential hypertension: results of a placebo-controlled randomized trial.
We tested the efficacy and safety of different combination therapies in hypertensive patients with uncontrolled blood pressure (BP) on a monotherapy with a calcium antagonist: 1,647 hypertensive patients were enrolled to receive placebo for 4 weeks followed by isradipine (ISR) 2.5 mg twice daily (b.i.d.) for 4 weeks. Nonresponders [diastolic BP (DBP) > 90 mm Hg] were randomly assigned to receive either the beta-blocker bopindolol 0.5 or 1 mg/day, the diuretic metolazone 1.25 or 2.5 mg/day, the angiotensin-converting enzyme (ACE) inhibitor enalapril 10 or 20 mg/day, ISR 5 mg b.i.d., or placebo. One hundred seventy-five receiving placebo dropped out; 93% (n = 1,376) of the 1,472 patients finished 4-week monotherapy with ISR. Sixty percent (n = 826) reached target BP, and 40% (n = 550) remained uncontrolled and were randomized. Regardless of dosage, all drugs led to a comparable reduction in BP except for the lower dosage of bopindolol and ISR 5 mg b.i.d., which were less effective in lowering systolic BP (SBP). The BP decrease achieved by combination therapy ranged from 10 to 15 mm Hg SBP and from 7 to 11 mm Hg DBP but remained unchanged with placebo. Side effects were minor, and only 2.4% of patients discontinued therapy because of side effects. The side-effect score for edema was lower with ISR plus diuretics than with other combinations, whereas the ACE inhibitor was associated with a higher score for cough. Monotherapy with a calcium antagonist normalizes BP in about two-thirds of patients when used in general practice.(ABSTRACT TRUNCATED AT 250 WORDS)
Lüscher
T F
TF
Department of Medicine, University Hospital Basel/Switzerland.
Waeber
B
B
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017275:Isradipine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008788:Metolazone / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010869:Pindolol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004656:Enalapril; D010869:Pindolol; C036007:bopindolol; D008788:Metolazone; D017275:Isradipine