AN EQUIVALENCE STUDY OF THE SAFETY AND EFFICACY OF A FIXED-DOSE COMBINATION OF PERINDOPRIL WITH INDAPAMIDE VERSUS FIXED-DOSE COMBINATIONS OF CAPTOPRIL WITH HYDROCHLOROTHIAZIDE AND ENALAPRIL WITH HYDROCHLOROTHIAZIDE IN THE TREATMENT OF HYPERTENSION

Objective: The aim of this multicenter, randomly allocated, double-bli nd, parallel-group study was to evaluate the equivalence of three fixe d-dose combination drugs in mild to moderate hypertension: perindopril + indapamide (4 + 1.25 mg), captopril + hydrochlorothiazide (50 + 25 mg) and enalapril + hydrochlorothiazide (20 + 12.5 mg). Patients and m ethods: After a single-blind, 4-week, placebo run-in phase, 527 patien ts (mean +/- SD age 54.5 +/- 1.2 years) with a supine diastolic blood pressure of 101.2 - 101.7 mmHg were randomly assigned to one of the th ree treatments for 8 weeks. The main evaluation criteria were diastoli c blood pressure and serum potassium concentration. Equivalence was as sessed on an intention-to-treat basis, using Schuirmann's method, whic h involves performing two one-tailed statistical tests on the data. Th irty-five patients were withdrawn From the study but there were no dif ferences between groups in the reasons for withdrawal. Results: Diasto lic blood pressure decreased by between 13.1 and 14.2 mmHg in the thre e groups. The 90% confidence intervals for the differences between per indopril+indapamide and the other treatments were -1.1, +1.7 mmHg for captopril + hydrochlorothiazide and -0.4, +2.6 mmHg for enalapril + hy drochlorothiazide. Schuirmann's test was highly statistically signific ant (P < 0.001 for perindopril + indapamide versus captopril + hydroch lorothiazide; P < 0.002 for perindopril + indapamide versus enalapril + hydrochlorothiazide), so that the two one-sided hypotheses that the treatments were not equivalent were rejected at the nominal level of a lpha = 0.05. Similarly, the safety of the treatments was equivalent in terms of serum potassium. The 90% confidence intervals of the differe nces between perindopril+indapamide and the other treatments were -8.7 , -1.6% for captopril + hydrochlorothiazide (P = 0.004) and -1.5, +2.7 % for enalapril + hydrochlorothiazide (P < 0.001). Conclusions: We con clude that the safety and efficacy of perindopril + indapamide, captop ril + hydrochlorothiazide and enalapril + hydrochlorothiazide were equ ivalent after 8 weeks of treatment in patients with mild to moderate h ypertension.