Evaluating the Effects of Fixed-Dose Combination of Perindopril + Amlodipine on Target Organ Damage in Patients with Arterial Hypertension (First Results of EPHES Trial)

H.D. Radchenko, L.O. Mushtenko, Yu.M. Sirenko, O.O. Torbas, S.M. Kushnir, O.A. Yarynkina, S.V. Potashev

Abstract


EPHES trial (Evaluation of influence of fixed dose combination Рerindopril/Amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) had aim to evaluate the efficacy of fixed-dose combination of perindopril + amlodipine in terms of blood pressure (BP) decrease and the dynamics of target organ damage patterns in patients with arterial hypertension (AH) with and without ischemic heart disease (IHD).
Primary analysis included the data from 30 patients with AH and without IHD, aged over 30 years. The levels of systolic (SBP) and/or diastolic BP (DBP) in treatment-naive patients at baseline should be ≥ 160 and/or 100 mmHg, but < 200/120 mmHg; in those who received monotherapy or dual combination therapy — ≥ 140/90 mmHg, but < 200/120 mmHg. All patients in randomization day were administered fixed-dose combination of perindopril/amlodipine in the initial dose of 5/5 mg once daily. If it is necessary (BP > 140/90 mmHg), doses of fixed-dose combination components increased gradually every 2 weeks up to 10/10 mg, and after 6 weeks of treatment, indapamide 1.5 mg, beta-blockers or alpha blockers were added. All patients underwent: measurement of body weight and height, office levels of SBP, DBP, and heart rate, ambulatory BP monitoring, determination of pulse wave velocity in elastic (PWVe) and muscular arteries, central SBP, biochemical blood count, electrocardiography, echocardiography with D-graphy, measurement of ankle-brachial index, intima-media thickness. The duration of follow-up was 12 months.
Treatment with fixed-dose combination of perindopril + amlodipine ensured achieving target levels of both SBP and DBP in 60 % of cases at the stage of 6 weeks. Addition of indapamide 1.5 mg daily (n = 12) and bisoprolol (n = 1) provide control of office SBP and DBP in 100 % of patients at 6 months of treatment phase. Reduction of office BP was accompanied by a significant decrease in average daily, daytime and nighttime BP, respectively, by 22.3 ± 0.1 mmHg, 19.6 ± 0.4 mmHg, 26.1 ± 0.2 mmHg and 8.2 ± 0.2 mmHg, 8.4 ± 0.1 mmHg, 7.9 ± 0.1 mmHg and the achievement of target average daily in 98.7 % of patients. The ratio of patients characterized as non-dippers decreased significantly from 50 to 23.3 %, as well as the variability of daytime SBP/DBP and nighttime SBP. The proportion of patients with morning rise of SBP over 55 mmHg significantly decreased from 60 to 20 %.
Central SBP significantly decreased from 142.8 ± 2.5 mmHg to 118.3 ± 2.7 mmHg (P < 0.001). In parallel, there was a significant (P < 0.001) reduction in growth index from 26.8 ± 1.9 % to 11.2 ± 1.7 %. The therapy effective in terms of blood pressure reduction resulted during the year in a probable regression of target organ damage: decrease in left ventricular hypertrophy (myocardial mass index reduced from 108.8 ± 5.5 g/m2 to 88.3 ± 5.3 g/m2, Cornell index — from 2,440.1 ± 67.9 mm • ms to 1,987.2 ± 66.8 mm • ms, left atrial size — from 41.1 ± 0.2 mm to 38.1 ± 0.3 mm), the level of albuminuria (from 53.3 ± 5.6 mg/day to 15.8 ± 3.2 mg/day), improvement of left ventricular diastolic function and the elastic properties of the aorta (PWVe decreased from 11.9 ± 0.7 m/s to 9.4 ± 0.8 m/s). Changes in left ventricular diastolic function and the level of albuminuria significantly and independently of changes in BP (both office and central) correlated with the changes of PWVe and growth index. Antihypertensive therapy based on a fixed combination of perindopril + amlodipine was well tolerated by patients (incidence of adverse reactions was 6.5 %).


Keywords


arterial hypertension; target organs; fixed-dose combination

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DOI: https://doi.org/10.22141/2224-1485.4.42.2015.80671

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