DOI: https://doi.org/10.22141/2224-1485.6.62.2018.153928

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

Abstract


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.


Keywords


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

References


Allemann Y., Fraile B., Lambert M., Barbier M., Ferber P., Izzo J.L. Jr. Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EXFAST) study // J. Clin. Hypertens. (Greenwich). — 2008. — Vol. 10. — P. 185-194.

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) // JAMA. — 2002. — Vol. 18, № 288(23). — P. 2981-2997.

Asmar R., Gosse P., Quere S. et al. Efficacy of morning and evening dosing of amlodipine/valsartan combination in hypertensive patients uncontrolled by 5 mg of amlodipine // Blood Press. Monit. — 2011. — Vol. 16. — P. 80-86.

Aranda P., Ruilope L.M., Calvo C. et al. Erectile dysfunction in essential arterial hypertension and effects of sildenafil: results of a Spanish national study // Am. J. Hypertens. — 2004. — Vol. 17(2). — P. 139-145

Baser O., Andrews L.M., Wang L., Xie L. Comparison of real world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free combination therapy // J. Med. Econ. — 2011. — Vol. 14. — P. 576-583.

Bhad P., Ayalasomayajula S., Karan R. et al. Evaluation of pharmacokinetic interactions between amlodipine, valsartan, and hydrochlorothiazide in patients with hypertension // J. Clin. Pharmacol. — 2011. — Vol. 51(6). — P. 933-942.

Boutouyrie P., Achouba A., Trunet P. et al. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study // Hypertension. — 2010. — Vol. 55 — P. 1314-1322.

Calhoun D.A., Crikelair N.A., Yen J., Glazer R.D. Amlodipine/valsartan/hydrochlorothiazide triple combination therapy in moderate/severe hypertension: secondary analyses evaluating efficacy and safety // Adv. Ther. — 2009. — Vol. 26. — P. 1012-1023.

Calhoun D.A., Lacourciere Y., Crikelair N., Jia Y., Gla­zer R.D. Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension // Curr. Med. Res. Opin. — 2013. — Vol. 29. — P. 901-910.

Doumas M., Tsakiris A., Douma S. et al. Factors affecting the increased prevalence of erectile dysfunction in Greek hypertensive compared with normotensive subjects // J. Androl. — 2006. — Vol. 27(3). — P. 469-477.

Destro M., Luckow A., Samson M., Kandra A., Brunel P. Efficacy and safety of amlodipine/valsartan compared with amlodipine monotherapy in patients with stage 2 hypertension: a randomized, double-blind, multicenter study: the EX-EFFeCTS Study // J. Am. Soc. Hypertens. — 2008. — Vol. 2. — P. 294-302.

Duan J., Chen J., Yin Q. et al. Pharmacokinetics of single and multiple oral doses of valsartan/amlodipine (80/5 mg) in healthy Chinese subjects // Int. J. Clin. Pharmacol. Ther. — 2012. — Vol. 50(1). — P. 33-43.

Greenstein A., Chen J., Miller H. et al. Does severity of ischemic coronary disease correlate with erectile function? // Int. J. Impot. Res. — 1997. — Vol. 9(3). — P. 123-126

Galle J., Schwedhelm E., Pinnetti S., Böger R.H., Wanner C.; VIVALDI investigators. Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy // Nephrol. Dial. Transplant. — 2008. — Vol. 23(10). — P. 3174-3183.

Flack J.M., Calhoun D.A., Satlin L., Barbier M., Hil­kert R., Brunel P. Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study // J. Hum. Hypertens. — 2009. — Vol. 23. — P. 479-489.

Hermida R.C., Ayala D., Calvo C. Optimal timing for antihypertensive dosing: focus on valsartan // Ther. Clin. Risk Manag. — 2007. — Vol. 3. — P. 119-131.

Hermida R.C., Ayala D.E., Fontao M.J. et al. Chronotherapy with valsartan/amlodipine fixed combination: improved blood pressure control of essential hypertension with bedtime do­sing // Chronobiol. Int. — 2010. — Vol. 27. — P. 1287-1303.

Hermida R.C., Ayala D.E., Mojon A. et al. Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk // J. Am. Coll. Cardiol. — 2011. — Vol. 58. — P. 1165-1173.

Hermida R.C., Calvo C., Ayala D.E. et al. Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects // Hypertension. — 2003. — Vol. 42. — P. 283-290.

Hoshino A., Nakamura T., Matsubara H. The bedtime administration ameliorates blood pressure variability and reduces urinary albumin excretion in amlodipine-olmesartan combination therapy // Clin. Exp. Hypertens. — 2010. — Vol. 32. —

P. 416-422.

Iqbal M., Khuroo A., Batolar L.S. et al. Pharmacokine­tics and bioequivalence study of three oral formulations of valsartan 160 mg: a single-dose, randomized, open-label, three-period crossover comparison in healthy Indian male volunteers // Clin. Ther. — 2010. — Vol. 32(3). — P. 588-596.

Jiang J., Tian L., Huang Y. et al. Pharmacokinetic profiles of hydrochlorothiazide alone and in combination with benazepril or valsartan in healthy Chinese volunteers: evaluation of the potential interaction // Int. J. Clin. Pharmacol. Ther. — 2011. — Vol. 49(12). — P. 756-764.

Sison J., Vega R.M.R., Hu Dayi, Bader G., Brunel Р. Efficacy and effectiveness of valsartan/amlodipine and valsartan/amlodipine/hydrochlorothiazide in hypertension: rando-mized-controlled versus observational studies // Current Medical Research and Opinion. — 2018. — 34(3). — 501-515. DOI: 10.1080/03007995.2017.1412682.

Kafrawy N.E., Rashwan M., Lion K., Khedr K., Nashaat N. Effectiveness and tolerability of fixed dose combination of amlodipine/valsartan in treatment of hypertension in the real-life setting among Egyptian patients // Egyptian Heart J. — 2014. — Vol. 66. — P. 30-35.

Kario K., Tomitani N., Kanegae H., Ishii H., Uchiyama K., Yamagiwa K., Shiraiwa T., Katsuya T., Yoshida T., Kanda K., Hasegawa S., Hoshide S. Comparative effects of an angiotensin II receptor blocker (ARB)/diuretic vs. ARB/calcium-channel blocker combination on uncontrolled nocturnal hypertension evaluated by information and communication technology-based nocturnal home blood pressure monitoring — the NOCTURNE Study // Circ. J. — 2017. — Vol. 81. — P. 948-957.

Kasichayanula S., Chang M., Liu X. et al. Lack of pharmacokinetic interactions between dapagliflozin and simva-statin, valsartan, warfarin, or digoxin // Adv. Ther. — 2012. — Vol. 29(2). — P. 163-177.

Khan W., Moin N., Iktidar S., Sakrani J., Abid R., Af-

zal J. et al. Real-life effectiveness, safety, and tolerability of amlodipine/valsartan or amlodipine/valsartan/hydrochlorothiazide singlepill combination in patients with hypertension from Pakistan // Ther. Adv. Cardiovasc. Dis. — 2014. — Vol. 8. — P. 45-55.

Matsui Y., Eguchi K., O’Rourke M.F. et al. Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients // Hypertension. — 2009. — Vol. 54. — P. 716-723.

Lenter C. Geigy Scientific Tables. — CIBA-GEIGY Corporation: Basel, 1990. — 278 p.

Lins R., Aerts A., Coen N., Hermans C., MacDonald K., Brie H. et al. Effectiveness of amlodipine-valsartan single-pill combinations: hierarchical modeling of blood pressure and total cardiovascular disease risk outcomes (the EXCELLENT study) // Ann. Pharmacother. — 2011. — Vol. 45. — P. 727-739.

Mallat S.G., Itani H.S., Tanios B.Y. Current perspectives on combination therapy in the management of hypertension // Integr. Blood Press. Control. — 2013. — Vol. 6. — P. 69-78.

Mancia G., Fagard R., Narkiewicz K., Redon J., Zanchetti A., Bohm M. et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // J. Hypertens. — 2013. — Vol. 31. — P. 1281-357.

Nakayama K., Kuwabara Y., Daimon M., Shindo S., Fujita M., Narumi H., Mizuma H., Komuro I. Valsartan Amlodipine Randomized Trial (VART): design, methods, and preliminary results // Hypertens. Res. — 2008. — Vol. 31(1). — P. 21-28. doi: 10.1291/hypres.31.21.

Mehlum M., Liestøl K., Julius S., Kjeldsen S.E., Hua T.A., Rothwell P.M., Mancia G., Parati G., Weber M.A., Berge E. Visit-to-visit blood pressure variability increases risk of stroke or cardiac events in patients given valsartan or amlodipine in the VALUE trial // J. Hypertens. — 2015. — Vol. 33, Suppl. 1. — e40. doi: 10.1097/01.hjh.0000467454.55397.ea.

Mizuguchi Y., Oishi Y., Tanaka H. et al. Arterial stiffness is associated with left ventricular diastolic function in patients with cardiovascular risk factors: early detection with the use of cardio-ankle vascular index and ultrasonic strain imaging // J. Card. Fail. — 2007. — Vol. 13. — P. 744-751.

Nakamura K., Tomaru T., Yamamura S., Miyashita Y., Shirai K., Noike H. Cardio-ankle vascular index is a candidate predictor of coronary atherosclerosis // Circ. J. — 2008. — Vol. 72. — P. 598-604.

Satoh N., Shimatsu А., Kato Y. et al. Evaluation of the Cardio-Ankle Vascular Index, a New Indicator of Arterial Stiffness Independent of Blood Pressure, in Obesity and Metabolic Syndrome // Hypertens. Res. — 2008. — Vol. 31 — P. 1921-1930.

Okeahialam B.N. Valsartan, an angiotensin receptor blocker treats sexual dysfunction in a female hypertensive: a case report // Afr. J. Med. Sci. — 2011. — Vol. 40(3). — P. 273-275.

Omboni S., Parati G., Palatini P. et al. Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study // J. Hypertens. — 1998. — Vol. 16. — P. 733-738.

Ostchega Y., Zhang G., Hughes J., Nwankwo T. Factors Associated with Hypertension Control in U.S. Adults Using 2017 ACC/AHAGuidelines: National Health and Nutrition Examination Survey 1999–2016 // Am. J. Hypertens. — 2018. — Vol. 29. doi: 10.1093/ajh/hpy047. [Epub ahead of print]

Periard D., Rey M.A., Casagrande D. et al. The effect of valsartan versus non-RAAS treatment on autoregulation of cerebral blood flow // Cerebrovasc. Dis. — 2012. — Vol. 34(1). — P. 78-85.

Parati G., Asmar R., Bilo G. et al. Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study // Hypertens Res. — 2010. — Vol. 33(10). — P. 986-994.

Pereira M., Lunet N., Azevedo A., Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries // J. Hypertens. — 2009. — Vol. 27. — P. 963-975.

Philipp T., Smith T.R., Glazer R. et al. Two multicenter, 8-week, randomized, double-blind, placebocontrolled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension // Clin. Ther. — 2007. — Vol. 29. — P. 563-580.

Pogue V., Rahman M., Lipkowitz M. et al. Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease // Hypertension. — 2009. — Vol. 53. — P. 20-27.

Safar M.E., Protogerou A., Blacher J. Central blood pressure under angiotensin and calcium channel blockade // Hypertension. — 2009. — Vol. 54. — P. 704-706.

Salles G.F., Reboldi G., Fagard R.H. et al. Prognostic effect of the nocturnal blood pressure fall in hypertensive patients: the Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) meta-analysis // Hypertension. — 2016. — Vol. 67. — P. 693-700.

Sawada T., Yamada H., Dahl f B., Matsubara H. for the KYOTO HEART Study Group. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study // Eur. Heart J. — 2009. — Vol. 30. — P. 2461-2469.

Shirai K., Utino J., Otsuka K., Takata M. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI) // J. Atheroscler. Thromb. — 2006. — Vol. 13. — P. 101-107.

Sison J., Assaad-Khalil S.H., Najem R., Kitchlew A.R., Cho B., Ueng K.C. et al. Real-world clinical experience of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide in hypertension: the EXCITE study // Curr. Med. Res Opin. — 2014. — Vol. 30. — P. 1937-1945.

Takaki A., Ogawa H., Wakeyama T. et al. Cardio-ankle vascular index is a new noninvasive parameter of arterial stiffness // Circ. J. — 2007. — Vol. 71. — P. 1710-1714.

Weycker D., Keskinaslan A., Levy D.G. et al. Effectiveness of add-on therapy with amlodipine in hypertensive patients receiving valsartan // Blood Press. Suppl. — 2008. — Vol. 2. — P. 5-12.

Yoshida H., Shimizu M., Ikewaki K. et al. Jikei Heart Study group. Sex differences in effects of valsartan administration on cardiovascular outcomes in hypertensive patients: findings from the Jikei Heart Study // J. Hypertens. — 2010. — Vol. 28(6). — P. 1150-1157.

Zakeri-Milani P., Valizadeh H., Islambulchilar Z., Nemati M. Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers // Arzneimittelforschung. — 2010. — Vol. 60(2). — P. 76-80.

Noike H., Nakamura K., Sugiyama Y. et al. Changes in cardio-ankle vascular index in smoking cessation // J. Atheroscler. Thromb. — 2010. — Vol. 17(5). — P. 517-525.

Wang L., Zhao J.W., Liu B., Shi D., Zou Z., Shi X.Y. Antihypertensive effects of olmesartan compared with other angiotensin receptor blockers: a meta-analysis // Am. J. Cardiovasc. Drugs. — 2012. — Vol. 12(5). — P. 335-344. doi: 10.2165/11597390-000000000-00000.




Copyright (c) 2019 HYPERTENSION

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© Publishing House Zaslavsky, 1997-2019

 

   Seo анализ сайта