Effectiveness of a Fixed-Dose, Single-Pill Combination of Perindopril and Amlodipine in Patients with Hypertension: A Non-Interventional Study

Abstract

Introduction: We conducted a prospective, non-interventional, multicenter study to examine the effect of a fixed-dose combination of perindopril/amlodipine in patients with arterial hypertension.

Methods: Patients who were previously untreated or required a change in medication were treated with a fixed combination of perindopril/amlodipine (3.5/2.5 or 7.0/5.0 mg) for 12 weeks. Changes in office, home and ambulatory blood pressure (BP) were recorded. Adherence was assessed by the Hill-Bone medication adherence scale.

Results: Overall, 1814 patients (mean age 60.0 ± 13.4 years) were included in 614 German practices, and data of 1770 patients were analyzed. At study entry, 97.7% of patients received perindopril/amlodipine at a daily dose of 3.5 mg/2.5 mg, and 47.9% of patients remained on this dose during the study period. Treatment with perindopril/amlodipine decreased mean office BP from 163.7/95.4 to 133.6/80.3 mmHg (p < 0.0001), resulting in a hypertension control rate of 69.1%. Blood pressure control was comparable in previously untreated and treated patients (70.3 vs. 68.1%), and in younger and older patients (70.6 < 65 vs. 66.3% ≥ 65 years). Ambulatory BP measurements were available in a subgroup of patients (n = 167), and mean 24 h ambulatory BP decreased from 150.6 ± 12.6/88.9 ± 8.8 to 132.4 ± 11.9/79.4 ± 8.5 mmHg (p < 0.0001). Furthermore, the proportion of patients with severe hypertension European Society of Hypertension/European Society of Cardiology (ESH/ESC) grade II or III decreased from 64.4 to 3.9%, and patients with pre-existing isolated systolic hypertension (n = 284) converted to normal BP in 67.6% of cases. Nearly half of the patients (47.2%) were perfectly adherent during the study. In previously treated patients, the percentage of patients with perfect adherence increased from 20.6% prior to study to 43.5% at final visit (p < 0.0001). Adverse drug reactions were documented for 4.9% of patients.

Conclusion: A fixed-dose combination of perindopril/amlodipine shows significant blood pressure reduction and improvement in medication adherence in a primary care setting.

Trial registration: ISRCTN26323538.

Funding: Servier Deutschland GmbH.

Keywords: Adherence; Amlodipine; Cardiology; Hypertension; Non-interventional study; Perindopril; Prospective; Single-pill combination.

Fig. 1

Antihypertensive treatment status at baseline. a Treatment status at baseline according to number of antihypertensive drugs (DC drug class) (n = 1814). b Prevalence of antihypertensive drug class (n = 980) at baseline

Fig. 2

Change in systolic and diastolic blood pressure. a Total population, office vs. home measurements (n = 1770/1282, LOCF). b Systolic and diastolic office blood pressure and heart rate (HR) in the LOCF study population over time (n = 1770 for BP, n = 1680 for HR). c 24 h-ABPM measurements available in subset of patients (n = 187 for day, 175 for night, 167 for all measurements, LOCF). ***p < 0.0001 vs. V1 (baseline)

Fig. 3

Changes in blood pressure in patient subgroups. a Patients with previous antihypertensive treatment (n = 967, LOCF) versus treatment naïve patients (n = 803, LOCF). b Patients younger than 65 years (n = 1133, LOCF) vs. patients older than 65 years (n = 636, LOCF)

Fig. 4

Treatment response, blood pressure classification according to ESH/ESC and tracking of patients with isolated systolic hypertension (ISH). a Overall Responder rates (RR < 140/90 mmHg at last observation) in patients with hypertension grade 1–3 at baseline in the total population (n = 1744) as well as in the subgroups of patients with previous antihypertensive medication (n = 947), without previous antihypertensive treatment (n = 797), patients younger than 65 years (n = 1120) and patients age 65 years and older (n = 623). b Classification of blood pressure according to the ESH/ESC-guidelines at admission and at the last observation: while initially 72.4% of patients had hypertension grade 2 or worse, this fraction is reduced to 5.2% at the last observation. c Reanalysis to track patients with ISH. Patients with ISH at baseline show good blood pressure control in > 67% at the last observation (n = 284). d Patients with ISH at the last observation showed mainly systolic/diastolic hypertension (SDH) at baseline (n = 323)

Fig. 5

Treatment adherence before and after switching to perindopril/amlodipine. Change in adherence rate to antihypertensive treatment in patients with previous antihypertensive treatment (n = 897) after switching to perindopril/amlodipine as well as in patients with newly treated hypertension. Perfect adherence rate is defined as percentage of patients who answer all items of the Hill-Bone Medications Adherence Scale with “none of the time”