Changes in office blood pressure and adherence to treatment in patients with arterial hypertension in TRIMARAN trial (Effectiveness of the generiIc drug Kombisart H and Kombisart (fixed combination of valsartan and amlodipine))

Yu.M. Sirenko, O.L. Rekovets, O.O. Torbas, S.M. Kushnir


Background. In spite of the wide possibilities of medical treatment, control of hypertension is not very good in the whole world. Many patients achieve a good result when using combination therapy and reach the target blood pressure level. However, about 2/3 of them take multicomponent antihypertensive therapy. The most effective fixed combinations of antihypertensive drugs include renin-angiotensin-aldosterone system blockers (blockers of angiotensin II receptors or angiotensin-converting enzyme inhibitors) in combination with calcium antagonists and/or diuretics. Purpose of this study was to evaluate the therapeutic efficacy of generic fixed triple combination of valsartan/amlodipine/hydrochlorothiazide and fixed double combination of valsartan/amlodipine in the treatment of patients with stage II–II hypertension. Materials and methods. The study included 50 patients with moderate and severe hypertension without diabetes mellitus. They were divided into 2 groups. A fixed triple combination of 160 mg valsartan/5 mg amlodipine/12.5 mg hydrochlorothiazide was administered to the first group (n = 25) once a day, in the morning for 1 month. Patients in the second group (n = 25) received a fixed double combination of 160 mg valsartan/5 mg amlodipine once a day, in the morning for 1 month, according to the same scheme. If after 1 month of therapy the target level of office blood pressure was achieved, patients continued to receive the prescribed therapy in the previous dose. If after 1 month of treatment the target level of office blood pressure < 140/90 mmHg was not achieved, patients of the first group received tablet of Kombisart H — 160 mg valsartan/10 mg amlodipine/12.5 mg hydrochlorothiazide for another 1 month. Patients in the second group received 1 tablet of Kombisart — 160 mg valsartan/10 mg amlodipine for another 1 month. If after 2 months of treatment the target level of office blood pressure < 140/90 mmHg was not achieved, patients of the first group were additionally administered 1 tablet of Kombisart (160 mg valsartan/5 mg amlodipine) with evening meal for another 1 month. Patients in the second group additionally received Kombisart H at a dose of 160 mg valsartan/10 mg amlodipine/12.5 mg hydrochlorothiazide per month. After 3 months of treatment, there was the control of therapy. Results. The study included 50 patients with moderate and severe hypertension. The average age of patients was 54.9 ± 1.8 (25–75) years. The average body weight was 92.4 ± 2.6 kg. The average body mass index — 31.2 ± 0.7 kg/m2.
The average office of systolic (SBP) and diastolic blood pressure (DBP) at baseline were 161.7 ± 1.8 mmHg and 98.5 ± 1.4 mmHg, respectively. The office heart rate was 70.7 ± 1.4 bpm. Average blood pressure levels at ambulatory monitoring were 140.8 ± 1.1 mmHg for SBP and 84.4 ± 1.2 mmHg for DBP. Average daily heart rate — 71.5 ± 1.5 bpm. Only 5 (10 %) patients had normal body weight, 17 (34 %) were overweight, 19 (38 %) had obesity degree I, 6 (12 %) — obesity degree II, 3 (6 %) persons — obesity degree III. A decrease in the office blood pressure (SBP/DBP) in general was 35.6/22.5 mmHg (p < 0.05), 35/19 mmHg (p < 0.05) on the double combination and 42/26 mmHg (p < 0.05) on the triple combination. The rate of achieving target BP in office monitoring was 93.3 % in the whole group, 90.9 % — on the double combination and 95.7 % — on triple combination. The triple combination was more effective in reducing office blood pressure compared to the double combination that was not accompanied by an increase in side effects. The withdrawal of the drug was observed in 7 (14 %) patients, mainly due to side effects in the form of palpitations and edema of the legs on the background of amlodipine administration. In the group of double combination, withdrawal was only in 3 (6 %) patients, in the triple combination group — in 4 (8 %). The double and triple fixed combination improved the patient’s adherence to treatment according to Morisky-Green questionnaire. Conclusions. Fixed generic combinations of valsartan/amlodipine and valsartan/amlodipine/hydrochlorothiazide were effective in reducing the level of office blood pressure in patients with moderate and severe hypertension, improving adherence to treatment and were well tolerated.


fixed combination; efficacy; arterial hypertension; valsartan; amlodipine; hydrochlorothiazide


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