Pooled analysis of the three trials of the TRIUMF series: efficacy of a triple fixed combination of antihypertensive drugs in the practice of physicians of different specialties in Ukraine

Abstract

Study objectives – to compare the data obtained in the TRIUMF (antihyperTensive theRapy in UkraIne – BP optiMization in Focus) trials, in particular, TRIUMF-1, TRIUMF-2, TRIUMF-3, to determine possible patterns and significant factors affecting BP control in patients taking 2 or more antihypertensive drugs and switching to the original single pill combination (SPC) of perindopril arginine/indapamide/amlodipine.
Materials and Methods. For the pooled analysis, data on 5960 patients obtained from the three trials of the TRIUMF series were selected. All the studies were multicenter prospective trials conducted at different times in Ukraine with the involvement of general practitioners (TR-1), cardiologists (TR-2), and family practitioners (TR-3). According to the inclusion criteria, patients over 18 years of age with hypertension and a history of taking 2 or 3 antihypertensive drugs for at least 1 month whose BP remained above 140/90 mm Hg could be included in the study. The drug of choice for further therapy was Triplixam (Servier, France) – a single pill combination (SPC) of perindopril arginine, amlodipine and indapamide. Each patient was observed for 3 months. Patients visited physicians in 1–2 weeks, 2 months after the start of the study and the corresponding therapy adjustment. The adherence rate was assessed before and after 2 months. The use of beta-blockers (BBs) in the treatment of the cohort of patients with hypertension was analyzed separately. The final analysis included a comparison of the data obtained in the TRIUMF trial series.
Results and Discussion. The use of a SPC of perindopril arginine/indapamide/amlodipine allowed to achieve the target BP levels (140/90 or less) after 2 months of therapy in 84 % of patients with a history of taking a combination therapy (2 drugs – 65 %, 3 drugs – 35 %). One of the important criteria for choosing the dose of a triple SPC is the baseline BP values. The higher the degree of hypertension, the higher the dose prescribed by physicians. The minimum dose of the SPC of perindopril arginine, indapamide and amlodipine (5/1.25/5 mg) was prescribed for stage 1 hypertension in 62 %, stage 2 hypertension in 38 %, and stage 3 hypertension in 15 % of patients; the maximum dose (10/2.5/10 mg) was prescribed for stage 1 hypertension in 9 %, stage 2 hypertension in 15 %, and stage 3 hypertension in 43 % of patients included in the study (p<0.05). Therapy with the triple SPC of perindopril arginine, indapamide and amlodipine was well tolerated: adverse events were observed in 0.63 % (TR-1), 1 % (TR-3) and 1.86 % (TR-2) of cases, which was largely due to the previous use of two (65 %) or three (35 %) antihypertensive drugs comprising the SPC by the study patients. Beta-blockers (n=2012) were prescribed due to the presence of a comorbidity (coronary heart disease, angina pectoris – 33.5 %, heart failure – 28.3 %) rather than due to lowered BP. The combination of perindopril arginine/indapamide/amlodipine with BB was well tolerated and 83.9 % of patients achieved BP ≤ 140/90 mm Hg, while 9.36 % achieved 
≤ 130/80 mm Hg after 2 months of treatment. There was a significant improvement in the adherence to treatment (TR-2, TR-3) in the majority of patients (75 and 70 %), due to high antihypertensive efficacy, convenience of pill’s administration (one pill instead of three) and good tolerability of the original SPC.
Conclusions. Regular medical supervision (cardiologists, family practitioners, general practitioners), high antihypertensive efficacy of the SPC (84 % of patients reached the target BP levels after 2 months of therapy ), convenience of pill’s administration (one pill instead of three), high adherence to treatment confirmed in TR-2 and TR-3 in most patients, and good tolerability of the original SPC of perindopril arginine, indapamide and amlodipine led to a significant improvement in the effectiveness of treatment of patients with hypertension.