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Influence of fixed-dose combination perindopril/amlodipine on target organ damage in patients with arterial hypertension with and without ischemic heart disease (results of EPHES trial)

Authors Radchenko GD, Mushtenko LO, Sirenko YM

Received 24 January 2018

Accepted for publication 23 July 2018

Published 11 October 2018 Volume 2018:14 Pages 265—278


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Daniel Duprez

Ganna D Radchenko, Liliya O Mushtenko, Yuriy M Sirenko

State Institute “National Scientific Center “Institute of Cardiology named after acad.M.Strazhesko” of Ukrainian National Academy of Medical Science, Kyiv, Ukraine

Background: The EPHES trial (Evaluation of influence of fixed dose combination Perindopril/amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) compared the dynamics of target organ damage (TOD) in hypertensive patients with and without ischemic heart disease (IHD) treated with the fixed-dose combination (FDC) perindopril + amlodipine.
Methods: The analysis included 60 hypertensive patients (aged >30 years): 30 without IHD and 30 with IHD. At randomization, FDC was administered at a daily baseline dose of 5/5 mg with uptitration to 10/10 mg every two weeks. If target blood pressure (BP<140/90 mmHg) was not achieved after six weeks, indapamide 1.5 mg was added to the regimen. All patients underwent body mass index measurements, office and ambulatory BP measurements, pulse wave velocity (PWVe) and central systolic BP evaluation, augmentation index adjusted to heart rate 75 ([email protected]) evaluation, biochemical analysis, ECG, echocardiography with Doppler, ankle-brachial index measurement, and intima-media thickness measurement. The follow-up period was 12 months.
Results: Therapy based on FDC perindopril/amlodipine was effective in lowering BP (office, ambulatory, central) in both groups. We noted significant decrease in [email protected] with the therapy in both groups, but Δ[email protected] was lesser in the group with IHD than the group without IHD. FDC provided significant improvement in PWVe and left ventricular diastolic function, and decrease in albuminuria, left ventricular hypertrophy (LVH), and left atrium size. ΔPWVe was significantly (P<0.005) less in patients without IHD than those with IHD (2.5±0.2 vs 4.4±0.5 m/s, respectively). In spite of almost equal LVH regression, the positive dynamics of ΔE/A and ΔE/E´ were more in patients with IHD than those without IHD (64.4% and 54.1% vs 39.8 and 23.2%, respectively; P<0.05 for both comparisons). Adverse reactions were in 2 (6.5%) patients without IHD and 3 (10%) with IHD (P=NS). In the group with IHD, we noted significant decrease in angina episode rate – from 2.5±0.4 to 1.2±0.2 (P<0.01) per week.
Conclusion: Thus, treatment based on FDC was effective in decreasing BP and TOD regression in both patients with and without IHD. However, the dynamics of changes in TOD were different between the two groups, which should be taken into consideration during management of patients with and without IHD.

Keywords: arterial hypertension, ischemic heart disease, target organ damage regression, fixed-dose combination, prospective observation, perindopril, amlodipine

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