Assessment of adherence to therapy in comorbid patients

Objective. To evaluate adherence to therapy in patients with hypertension (HTN) and atrial fibrillation (AF) in combination with extracardiac comorbid pathology. Design and methods. In an observational cohort study, 884 patients aged 45–65 years with AF (paroxysmal and persistent form) and HTN were observed, in combination with extracardiac comorbid diseases: diabetes mellitus (DM), n = 123; abdominal obesity (AO), n = 171; chronic obstructive pulmonary disease (COPD), n = 137, hypothyroidism, n = 156; thyrotoxicosis, n = 112. The comparison group consisted of 185 patients with AF and HTN, without concomitant extracardiac pathology. Clinical, anthropometric parameters, the Morischi–Green adherence test were evaluated in the work. To assess the social aspects of low adherence, special questionnaires were developed. All statistical calculations were performed using the Rstudio program. Results. Among patients with AF and HTN, 66 % had concomitant extracardiac comorbid pathology, 20 % of them with DM; COPD was detected in 22 % of patients, and AO was observed in 44 % of patients, 6 % patients had thyroid disease. 15,2 % patients were insufficiently adherent (ADH), 37,2 % were not adherent to therapy (NADH), and only 47,8 % respondents were adherent to therapy. The duration of HTN was not a significant motivation for adherence, because the NADH group had a significantly longer duration of arterial hypertension compared with the ADH group (12.3 vs 10.5 years; p < 0.03); patients with the permanent form of AF were more than ADH (p = 0,001), and the adherence did not differ between groups depending on extracardiac diseases. The blockers of the renin-angiotensin-aldosterone system showed the greatest use — up to 66 %, while adherent patients were more likely to take single-pill combination (SPC) of perindopril (SPC indapamide/perindopril and SPC amlodipine/indapamide/perindopril) (p = 0,003; p = 0,01). Based on the analysis, it was found that the presence of a family, higher education, income level, motivation and trust in doctors are significant factors that increase adherence to treatment. Conclusions. The problem of non-commitment has been and remains one of the most complex and difficult to solve. The main reason for low adherence among patients with AF with concomitant extracardiac diseases was polypharmacy, and it is associated with the use of a large number of drugs and a complex treatment regimen. Thus, the limitation of the use of fixed combinations is one of the main reasons for the lack of adherence and needs to be addressed soon.

1. Lukina YuV, Kutishenko NP, Martsevich SYu. Treatment adherence: modern view on a well known issue. Cardiovascular Therapy and Prevention. 2017;16(1):91–95. doi:10.15829/1728-8800-2017-1-91-95. In Russian.

2. Arakelyan MG, Bockeria LA, Vasilieva EYu, Golitsyn SP, Golukhova EZ, Gorev MV et al. 2020 Clinical guidelines for atrial fibrillation and atrial flutter. Russian Journal of Cardiology. 2021;26(7):4594. doi:10.15829/1560-4071-2021-4594. In Russian.

3. The results of the ESC Congress. European clinical guidelines, what’s new? Russian Journal of Cardiology. 2021;26(3S):4684. doi:10.15829/1560-4071-2021-4684. In Russian.

4. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Russian Journal of Cardiology. 2017;(7):7–86. doi:10.15829/1560-4071-2017-7-7-86. In Russian.

5. Apostolakis S, Sullivan RM, Olshansky B, Lip GYH. Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM trial. Int J Cardiol. 2014;170(3):303–308. doi:10.1016/j.ijcard.2013.11.002

6. Wyse DG. Idiopathic atrial fibrillation revisited in a large longitudinal clinical cohort. Europace. 2012;14(2):151–152. doi:10.1093/europace/eur379

7. Weijs B, Pisters R, Nieuwlaat R, Breithardt G, Le Heuzey JY, Vardas PE et al. Idiopathic atrial fibrillation revisited in a large longitudinal clinical cohort. Europace. 2012;14(2):184–190. doi:10.1093/europace/eur379

8. Ogawa H, An Y, Ikeda S, Aono Y, Doi K, Ishii M et al. Progression from paroxysmal to sustained atrial fibrillation is associated with increased adverse events. Stroke. 2018;49:100–116. URL: http://www.umin.ac.jp/ctr

9. Clarke R, Lewington S. 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 Glob Health. 2018;6(6):641–49. doi:10.1016/S2214-109X(18)30217-1

10. Mathers CD, Loncar DP, Lo S. Projections of global mortality and burden of disease. Medicine. 2017;8:209–224. doi:10.1371/journal.pmed.0030442

11. Association of General Practitioners (Family Doctors) of the Russian Federation, National Medical Association for the Study of Combined Diseases, Professional Foundation for the Promotion of Medicine “PROFMEDFORUM” Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Cardiovasc Ther Prev. 2019;18(1):5–66. doi:10.15829/1728-8800-2019-1-5-66

12. Lip G, Coca А, Kahan T, Boriani G, Manolis AS, Olsen MH et al. Aconsensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE). Europace. 2017;19(6):891–911. doi:10.1093/europace/eux091

13. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906. doi:10.1016/S0140-6736(05)67185-1

14. Van Dulmen S, Sluijs E, van Dijk L, de Ridder D, Heerdink R, Bensing J et al. Patient adherence to medical treatment: a review of reviews. BMC Health Serv Res. 2007;7:55. doi:10.1186/1472-6963-7-55

15. Pruijm M, Schneider MP, Burnier M. Patient adherence and the pharmacological treatment of arterial hypertension. ESH Sci Letter. 2010;11(7). URL: www.viamedical.pl

16. Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA et al. Medication compliance and persistence terminology and definition. Value Health. 2008;11(1):44-47.

17. Cleland JGF, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) Eur Heart J. 2006;27(19):2338–2345. doi:10.1093/eurheartj/ehl250

18. Neaton JD, Wentworth D for the multiple risk factor intervention Trial Group. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease: overall findings and differences by age for 316,099 white men. Arch Intern Med. 1992;152(1):56–64. doi:10.1002/9781118596005.ch47

19. Ferrari R for the PREAMI investigators. Effects of ACE inhibition with perindopril on left ventricular remodeling and clinical outcome. Arch Intern Med. 2006;166(6):659–666. doi:10.1001/archinte.166.6.659

20. Jamerson KA, Weber MA, Bakris GL, Dahlof B, Pitt B, Shi V et al., on behalf of the ACCOMPLISH investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–2428. doi:10.1056/nejmoa0806182

21. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L et al. Outcomes in hypertensive patients at high cardiovascular risk treated with valsartan or amlodipine-based regimens: VALUE, a randomised trial. Lancet. 2004;363(9426):2022–2031. doi:10.1016/s0140-6736(04)16451-9

22. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH et al. INVEST Investigators. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. J Am Med Assoc. 2003;290(21):2805–2816. doi:10.1001/jama.290.21.2805

23. Khidirova LD, Yakhontov DA. The frequency and nature of complications against the background of drug and electrical cardioversion in patients with AF with GB in combination with extracardial comorbid pathology and adherence to treatment. Med Alphabet. 2019;31(406):34–47.

24. SYMBIO: Results of a longitudinal study of optimized blood pressure lowering therapy with fixed combination perindopril/amlodipine. ESH. 2010. doi:10.1097/01.hjh.0000378493.95521.3a

25. The Task Force for the management of arterial hypertension of the European Society of Hypertension and of the European Society of Cardiolody. 2007 Guidelines for the management of arterial hypertension. J Hypertens. 2007;25(6):1105–1187. doi:10.1097/HJH.0b013e3281fc975a

26. The ALLHAT Officers and Coordinators. Major outcomes in high-risk hypertensive patients randomized to ACE inhibitor or calcium channel blocker vs diuretic (ALLHAT). J Am Med Assoc. 2002;288(23):2981–2997. doi:10.1001/jama.288.23.2981

27. The EUROPA investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–788. doi:10.1016/s0140-6736(03)14286-9

28. The PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033–1041. doi:10.1016/S0140-6736(01)06178-5

29. Knorre DG. Biological chemistry. D.G. Knorre, S.D. Myzina. M.: Higher School, 2016;480.

30. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrӧm-Lundqvist C et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Russian Journal of Cardiology. 2021;26(9):4701. doi:10.15829/1560-4071-2021-4701. In Russian.

31. Parish RC, Miller LJ. Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. Drug Saf. 1992;7(1):14–31.

32. Nagai R, Kinugawa K, Inoue H, Atarashi H, Seino Y, Yamashita T et al., J-Land Investigators. Urgent management of rapid heart rate in patients with atrial fibrillation/flutter and left ventricular dysfunction: comparison of the ultra-short-acting ß1-selective blocker landiolol with digoxin (J-Land Study). Circ J. 2013;77(4):908-16.