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

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Abstract

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 II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), or was added to antihypertensive treatment with calcium channel blockers (CCBs), diuretics, or β-adrenoceptor antagonists (β-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 (−18.5/−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.

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Acknowledgments

The authors have received honoraria, research grants, or both, from Servier, Canada. The authors have no other relevant affiliations or financial involvement with any organization or entity in conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Furthermore, according to the rules and regulations of good clinical practice, none of the authors received any financial assistance for conducting this study, nor did they receive any monetary aid for the preparation of this manuscript.

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Authors and Affiliations

  1. McGill University Health Centre, Montreal, Quebec, Canada

    George Tsoukas

  2. Dr Georges-L. Dumont Regional Hospital, Moncton, New Brunswick, Canada

    Sanjiv Anand

  3. University of British Columbia, Surrey, British Columbia, Canada

    Kwang Yang

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  1. George Tsoukas
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  2. Sanjiv Anand
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  3. Kwang Yang
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Tsoukas, G., Anand, S., Yang, K. et al. Dose-Dependent Antihypertensive Efficacy and Tolerability of Perindopril in a Large, Observational, 12-Week, General Practice-Based Study. Am J Cardiovasc Drugs 11, 45–55 (2011). https://doi.org/10.2165/11587000-000000000-00000

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  • DOI: https://doi.org/10.2165/11587000-000000000-00000

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