Dose-Dependent Antihypertensive Efficacy and Tolerability of Perindopril in a Large, Observational, 12-Week, General Practice-Based Study

Background: Current guidelines recommend the use of full therapeutic dosages of antihypertensive agents, or combination therapy, to improve BP control of hypertensive patients in primary healthcare. Objective: The aim of this study was to assess the dose-dependent antihypertensive efficacy and safety of perindopril 4 and 8 mg/day in the clinical setting. Study Design and Setting: The CONFIDENCE study was a prospective, observational, multicenter trial. This was a real-world, clinic-based, outpatient study involving 880 general practitioners/primary-care clinics and 113 specialists in Canada. Patients: The study included untreated or inadequately managed patients with hypertension (i.e. seated BP >= 140/90 mmHg, or >= 130/80 mmHg in the presence of diabetes mellitus, renal disease, or proteinuria) without coronary artery disease (CAD). Intervention: Treatment consisted of perindopril 4 mg/day, uptitrated to 8 mg/day as required for BP control at visit 2, for 12 weeks. Among the patients already being treated at baseline, perindopril either directly replaced all previous ACE inhibitors or angiotensin H type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), or was added to antihypertensive treatment with calcium channel blockers (CCBs), diuretics, or beta-adrenoceptor antagonists (beta-blockers). Main Outcomes Measures: The primary outcomes were the mean changes in BP from baseline following treatment with perindopril 4 and 8 mg/day as well as the proportion of patients achieving BP control (BP <140/90 mmHg, or <130/80 mmHg in diabetic patients) in the intent-to-treat (ITT) population. Secondary analyses included the incidence of adverse events and compliance. Results: A total of 8298 hypertensive patients entered the study: 56% with newly diagnosed hypertension and 44% with uncontrolled hypertension. Mean SBP/DBP decreased significantly from baseline (152.5 +/- 10.8/89.5 +/- 9 mmHg) over 12 weeks (-18.51-9.7 mmHg; p <0.001). At visit 2,23% of patients were uptitrated to perindopril 8 mg/day, which resulted in an additional mean 10.1/5.3 mmHg BP reduction; this reduction was even greater (15.1/5.7 mmHg) among a separate group of severely hypertensive patients (i.e. SBP >170 mmHg or DBP >109 mmHg at baseline). Target BP was achieved in 54% of the ITT population. Both perindopril 4 mg/day and perindopril 8 mg/day were well tolerated and compliance was high throughout the study. Conclusion: In the clinical outpatient setting, perindopril was found to be an effective dose-dependent and well tolerated antihypertensive treatment, with good compliance. Uptitration to the full therapeutic dosage of perindopril is an efficient approach for the management of a broad range of hypertensive patients without CAD.