Adherence to treatment in patients with resistant arterial hypertension

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O. L. Rekovets
Yu. M. Sirenko


The aim – to identify patients with true resistant arterial hypertension and to assess patients’ adherence to treatment on the background of a fixed combination of antihypertensive drugs.
Materials and methods. 1146 patients with resistant hypertension were included in the study. Men and women over the age of 18 were included, provided that the average level of office blood pressure (BP) was greater than 140/90 mm Hg, when taking 3 or more antihypertensive drugs. Morisky – Green Questionnaire (in a modified scale) (MMAS-8) on patient adherence to treatment. To determine adherence to treatment in some patients, determination of drugs in urine was carried out in the central laboratory. All patients were initially subjected to the following tests: measurement of office SBP, DBP and heart rate, daily monitoring of BP, biochemical blood test.
Results and discussion. 51.4 % of patients took 3 antihypertensive drugs. 48.6 % took 4-6 antihypertensive drugs: among them, 4 drugs – 37.1 %, 9.1 % – took 5 drugs, and 2.4 % – 6 drugs. The degree of decrease in office BP among patients taking 3 or more antihypertensive drugs was 43.47 ± 0.65 mm Hg for systolic BP, and 20.33 ± 0.74 mm Hg for diastolic BP (p<0.001 for both values). 355 (31 %) patients failed to achieve the target level of office BP. They had true resistant hypertension. According to the Morisky – Green adherence questionnaire, on the background of the fixed triple combination of valsartan/amlodipine/hydrochlorothiazide, there was a significant improvement in adherence for all questions of the questionnaire. Patients began to forget to take pills significantly less, therapy became stable and regular, there were much fewer cases of stopping taking drugs due to deterioration of the patient’s condition after taking them, all 100 % of patients took antihypertensive drugs on the eve of the visit to the doctor, patients stopped canceling therapy due to their well-being at against the background of treatment, much fewer patients were bothered by the inconvenient regimen of taking drugs. Patient pill size was significant in only 11.4 % of patients at baseline and did not significantly change after 3 months of treatment with the fixed triple combination. But if patients had a choice, 60 % of them would choose the smaller pill. According to the determination of drugs in urine among 12 patients, we found that 25 % of patients (n=3) did not take drugs at all.
Conclusions. Resistant arterial hypertension was found in 31 % of patients taking 3 or more antihypertensive drugs. When determining adherence to treatment based on the detection of drugs in urine, 25 % of patients with resistant arterial hypertension did not take the prescribed drugs at all, that is, they had pseudoresistance.

Article Details


resistant arterial hypertension, adherence to treatment, pseudoresistance


Gorbas IM, Barna OM, Sakalosh VYu, Bakumenko MA. Assessment of the prevalence and control of cardiovascular disease risk factors among the population and physicians. Medicines of Ukraine. 2010;1:4-9.

Aslam S, Santha T, Leone A, Wilcox C. Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis [In Ukrainian]. Kidney Int. 2006;70(12):2109-15. doi: Epub 2006 Oct 25. PMID: 17063175.

Bhad P, Ayalasomayajula S, Karan R, Leon S, Riviere GJ, Sunkara G, Jarugula V. Evaluation of pharmacokinetic interactions between amlodipine, valsartan, and hydrochlorothiazide in patients with hypertension. J Clin Pharmacol. 2011;51(6):933-42. doi: Epub 2010 Sep 17. PMID: 20852001.

Bourgault C, Rainville B, Suissa S. Antihypertensive drug therapy in Saskatchewan: patterns of use and determinants in hypertension. Arch Intern Med. 2001;161(15):1873-9. doi: PMID: 11493129.

Boutouyrie P, Achouba A, Trunet P, Laurent S; EXPLOR Trialist Group. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study. Hypertension. 2010;55(6):1314-22. doi: Epub 2010 Apr 19. PMID: 20404219.

Butts B, Calhoun DA, Denney TS Jr, Lloyd SG, Gupta H, Gaddam KK, Aban I, Oparil S, Sanders PW, Patel R, Collawn JF, Dell'Italia LJ. Plasma xanthine oxidase activity is related to increased sodium and left ventricular hypertrophy in resistant hypertension. Free Radic Biol Med. 2019;134:343-349. doi: Epub 2019 Jan 26. PMID: 30695690; PMCID: PMC6588431.

Calhoun DA, Lacourcière Y, Chiang YT, Glazer RD. Triple antihypertensive therapy with amlodipine, valsartan, and hydrochlorothiazide: a randomized clinical trial. Hypertension. 2009;54(1):32-9. doi: Epub 2009 May 26. PMID: 19470877.

Calvo E, Izquierdo S, Castillo R, César E, Domene G, Gómez AB, Guerrero C, Andreu-Periz L, Gómez-Hospital JA, Ariza-Solé A. Can an individualized adherence education program delivered by nurses improve therapeutic adherence in elderly people with acute myocardial infarction?: A randomized controlled study. Int J Nurs Stud. 2021;120:103975. doi: Epub 2021 May 10. PMID: 34102371.

Corrao G, Nicotra F, Parodi A, Zambon A, Heiman F, Merlino L, Fortino I, Cesana G, Mancia G. Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension. 2011;58(4):566-72. doi: Epub 2011 Aug 8. PMID: 21825231.

Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM; ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4(6):393-404. doi: PMID: 12461301.

de Boer IH, Heerspink HJL, Hurst C, Khunti K, Liew A, Michos ED, Navaneethan SD, Olowu WA, Sadusky T, Tandon N, Tuttle KR, Wanner C, Wilkens KG, Zoungas S, Lytvyn L, Craig JC, Tunnicliffe DJ, Howell M, Tonelli M, Cheung M, Earley A, Rossing P. Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment. Kidney Int. 2020;98(4):839-48. doi:

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;2(4):294-302. doi: Epub 2008 Jun 2. PMID: 20409909.

Dragomir A, Côté R, Roy L, Blais L, Lalonde L, Bérard A, Perreault S. Impact of adherence to antihypertensive agents on clinical outcomes and hospitalization costs. Med Care. 2010;48(5):418-25. doi: PMID: 20393367.

Flack JM. Epidemiology and unmet needs in hypertension. J Manag Care Pharm. 2007;13(8 Suppl B):2-8. doi: PMID: 17970612.

Fogari R, Zoppi A, Derosa G, Mugellini A, Lazzari P, Rinaldi A, Fogari E, Preti P. Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens. 2007;21(3):220-4. doi: Epub 2007 Jan 11. PMID: 17215848.

Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, Carroll BA, Eliasziw M, Gocke J, Hertzberg BS, Katanick S, Needleman L, Pellerito J, Polak JF, Rholl KS, Wooster DL, Zierler RE. Carotid artery stenosis: gray-scale and Doppler US diagnosis – Society of Radiologists in Ultrasound Consensus Conference. Radiology. 2003;229(2):340-6. doi:

Holmqvist L, Boström KB, Kahan T, Schiöler L, Qvarnström M, Wettermark B, Hjerpe P, Hasselström J, Manhem K. Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD). Pharmacoepidemiol Drug Saf. 2018;27(3):315-21. doi: Epub 2018 Jan 19. PMID: 29349834.

Kjeldsen SE, Jamerson KA, Bakris GL, Pitt B, Dahlöf B, Velazquez EJ, Gupte J, Staikos L, Hua TA, Shi V, Hester A, Tuomilehto J, Ostergren J, Ibsen H, Weber M; Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension Investigators. Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: the ACCOMPLISH study. Blood Press. 2008;17(1):7-17. doi: PMID: 18568687.

Neutel JM, Smith DH. Improving patient compliance: a major goal in the management of hypertension. J Clin Hypertens (Greenwich). 2003;5(2):127-32. doi: PMID: 12671325; PMCID: PMC8101871.

Oparil S, Giles T, Ofili EO, Pitt B, Seifu Y, Hilkert R, Samuel R, Sowers JR. Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy. J Hypertens. 2011;29(1):161-70. doi: PMID: 21045734; PMCID: PMC3682653.

Philipp T, Smith TR, Glazer R, Wernsing M, Yen J, Jin J, Schneider H, Pospiech R. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, 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;29(4):563-80. doi: PMID: 17617280.

Poldermans D, Glazes R, Kargiannis S, Wernsing M, Kaczor J, Chiang YT, Yen J, Gamboa R, Fomina I. Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension. Clin Ther. 2007;29(2):279-89. doi: PMID: 17472820.

Schrader J, Salvetti A, Calvo C, Akpinar E, Keeling L, Weisskopf M, Brunel P. The combination of amlodipine/valsartan 5/160 mg produces less peripheral oedema than amlodipine 10 mg in hypertensive patients not adequately controlled with amlodipine 5 mg. Int J Clin Pract. 2009;63(2):217-25. doi: PMID: 19196360; PMCID: PMC2705817.

Simpson J, Jackson CE, Haig C, Jhund PS, Tomaszewski M, Gardner RS, Tsorlalis Y, Petrie MC, McMurray JJV, Squire IB, Gupta P. Adherence to prescribed medications in patients with heart failure: insights from liquid chromatography-tandem mass spectrometry-based urine analysis. Eur Heart J Cardiovasc Pharmacother. 2021;7(4):296-301. doi: PMID: 32597982; PMCID: PMC8302254.

Solomon SD, Verma A, Desai A, Hassanein A, Izzo J, Oparil S, Lacourciere Y, Lee J, Seifu Y, Hilkert RJ, Rocha R, Pitt B; Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction Investigators. Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction. Hypertension. 2010;55(2):241-8. doi: Epub 2009 Dec 7. PMID: 19996069.

Tomaszewski M, White C, Patel P, Masca N, Damani R, Hepworth J, Samani NJ, Gupta P, Madira W, Stanley A, Williams B. High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis. Heart. 2014;100(11):855-61. doi: Epub 2014 Apr 2. PMID: 24694797; PMCID: PMC4033175.

Trenkwalder P, Schaetzl R, Borbas E, Handrock R, Klebs S. Combination of amlodipine 10 mg and valsartan 160 mg lowers blood pressure in patients with hypertension not controlled by an ACE inhibitor/CCB combination. Blood Press Suppl. 2008;2:13-21. doi: PMID: 19205092.

Volpe M, Brommer P, Haag U, Miele C. Efficacy and tolerability of olmesartan medoxomil combined with amlodipine in patients with moderate to severe hypertension after amlodipine monotherapy: a randomized, double-blind, parallel-group, multicentre study. Clin Drug Investig. 2009;29(1):11-25. doi: PMID: 19067471.

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi: Erratum in: Eur Heart J. 2019 Feb 1;40(5):475. PMID: 30165516.

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-13. doi: Erratum in: Lancet. 2003 Mar 22;361(9362):1060. PMID: 12493255.

Rekovets OL, Torbas OO, Kushnir SM, Ponomareva GV, Primak GF, Granich VM, Krushinska NA, Polishchuk SA, Sydorenko PI, Sirenko YuM. Structure of patients with resistant arterial hypertension [In Ukrainian]. Arterial hypertension. 2018;1(57):46-66.

Rekovets OL, Sirenko YuM, Torbas OO, Kushnir SM, Primak GF. Changes in blood pressure during daily monitoring in hypertensive patients in the Trimaran trial (advantages of a triple fixed combination over a double) [In Ukrainian]. Arterial hypertension. 2019;1(63):17-32.

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