Short report: Ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design

摘要: Objective To identify appropriate dosages of ramipril and hydrochlorothiazide (HCT) when given in combination once a day for the treatment essential hypertension. Design A 2- or 4-week placebo run-in followed by 6-week, double-blind, parallel-group phase: 4 x 3 factorial (2.5, 5 10 mg ramipril; 12.5 25 HCT; all six combinations; placebo). Setting Office practice (21 centres). Patients participants with mild-to-moderate hypertension (World Health Organization stage I-II; supine diastolic blood pressure 100-115 mmHg last 2 weeks run-in): 581 enrolled, 534 randomly assigned to double-blind therapy 517 completed. Main outcome measures Reduction standing pressure. Results In pairwise comparisons, combinations HCT consistently produced significantly greater reductions than their respective components. Response surface analyses were performed, stairstep model was constructed characterize shape dose-response surface. The involving again more effective Withdrawals adverse effects minimal treatments. large drop serum potassium observed on HCT, but not therapy. Addition appeared reduce hyperuricaemic effect HCT. Conclusions Several dosage plus monotherapies at same dosages. Overall, gave best mean reduction. Combination safe patients