Evaluation of a Fixed-Dose Combination Antihypertensive Therapy versus Monotherapy on Medication Adherence and Blood Pressure Control: A Prospective Cohort Study
DOI:
https://doi.org/10.36283/ziun-pjmd15-1/017Keywords:
Blood Pressure, Cardiovascular Diseases, Essential Hypertension, Medication Compliance, Therapeutic AdherenceAbstract
Background: Suboptimal medication adherence represents a critical obstacle to achieving target blood pressure levels in hypertensive patients globally. Fixed-dose combination (FDC) formulations have demonstrated potential for enhancing therapeutic compliance through streamlined dosing protocols and reduced medication complexity. To evaluate comparative effectiveness of fixed-dose combination antihypertensive regimens versus conventional monotherapy and free-combination approaches regarding medication adherence patterns and blood pressure management outcomes.
Methods: This 6-month prospective observational cohort study recruited 1,248 treatment-naïve adults (ages 35-75) with newly diagnosed essential hypertension from three metropolitan primary care centers in Hyderabad, Pakistan between January and July 2025. Primary endpoint assessed medication adherence via proportion of days covered (PDC) methodology. Secondary endpoints included blood pressure target achievement rates, time-to-control intervals, and major adverse cardiovascular events.
Results: FDC recipients (n=624) exhibited substantially superior medication adherence versus control participants (n=624), with mean PDC values of 82.4% compared to 64.7% (p<0.001). Target blood pressure achievement (<140/90 mmHg) at 6 months occurred in 73.1% of FDC patients versus 54.8% of controls (p<0.001). Median time-to-target was significantly reduced in the FDC cohort (8.2 weeks vs. 12.6 weeks, p<0.001).
Conclusions: Single-pill combination antihypertensive strategies demonstrate marked superiority in medication adherence and blood pressure control metrics compared to traditional therapeutic approaches, supporting their prioritization in contemporary hypertension management protocols.
References
1. Burnier M, Damianaki A. Hypertension as cardiovascular risk factor in chronic kidney disease. Circulation research. 2023 Apr 14;132(8):1050-63. doi: 10.1161/CIRCRESAHA.122.321762.
2. Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, Paciorek CJ, Stevens GA, et al. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep;398(10304):957-980. doi: 10.1016/S0140-6736(21)01330-1.
3. Lee EK, Poon P, Yip BH, Bo Y, Zhu MT, Yu CP, et al. Global burden, regional differences, trends, and health consequences of medication nonadherence for hypertension during 2010 to 2020: a meta-analysis involving 27 million patients. J Am Heart Assoc. 2022 Sep;11(17):e026582. doi: 10.1161/JAHA.122.026582.
4. Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension. J Hypertens. 2023 Dec;41(12):1874-2071. doi: 10.1097/HJH.0000000000003480.
5. Yu D, Li JX, Cheng Y, Wang HD, Ma XD, Ding T, Zhu ZN. Comparative efficacy of different antihypertensive drug classes for stroke prevention: A network meta-analysis of randomized controlled trials. PLoS One. 2025 Feb 21;20(2):e0313309. doi: 10.1371/journal.pone.0313309.
6. Baryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nature reviews Drug discovery. 2023 May;22(5):387-409. doi: 10.1038/s41573-023-00670-0.
7. Shahid I, Khan MS, Fonarow GC, Butler J, Greene SJ. Bridging gaps and optimizing implementation of guideline-directed medical therapy for heart failure. Progress in Cardiovascular Diseases. 2024 Jan 1;82:61-9. doi: 10.1016/j.pcad.2024.01.008.
8. Wilkins CA, Hamman H, Hamman JH, Steenekamp JH. Fixed-dose combination formulations in solid oral drug therapy: advantages, limitations, and design features. Pharmaceutics. 2024 Jan 26;16(2):178. doi: 10.1111/jch.13426.
9. Zhou X, Zhang X, Gu N, Cai W, Feng J. Barriers and facilitators of Medication Adherence in Hypertension patients: a Meta-integration of qualitative research. J Patient Exp. 2024 Mar;11:23743735241241176. doi: 10.1177/23743735241241176.
10. Wei Q, Zhou J, Li H, Wang L, Wu Y, Ma A, et al. Medication adherence with fixed-dose versus free-equivalent combination therapies: Systematic review and meta-analysis. Front Pharmacol. 2023 Mar;14:1156081. doi: 10.3389/fphar.2023.1156081.
11. Davari M, Kebriaeezadeh A, Sorato MM, Soleymani F. Impact of Fixed Dose Combination Treatment on Adherence, Blood Pressure Control, Clinical Outcomes and Cost of Treatment. J Pharmacoecon Pharm Manag. 2022;8(3):1-4.
12. Jung MH, Lee SY, Youn JC, Chung WB, Ihm SH, Kang D, et al. Antihypertensive medication adherence and cardiovascular outcomes in patients with cancer: a nationwide population-based cohort study. J Am Heart Assoc. 2023 Jul;12(14):e029362. doi: 10.1161/JAHA.123.029362.
13. Yuan W, Zhang Y. Comparative different interventions to improve medication adherence in patients with hypertension: a network meta-analysis. J Cardiovasc Nurs. 2025 Jan-Feb;40(1):E9-E23. doi: 10.1097/JCN.0000000000001015.
14. Bujang MA, Omar ED, Foo DH, Hon YK. Sample size determination for conducting a pilot study to assess reliability of a questionnaire. Restorative dentistry & endodontics. 2024 Jan 10;49(1). doi: 10.5395/rde.2024.49.e3.
15. Katz ME, Mszar R, Grimshaw AA, Gunderson CG, Onuma OK, Lu Y, et al. Digital health interventions for hypertension management in US populations experiencing health disparities: a systematic review and meta-analysis. JAMA Netw Open. 2024 Feb;7(2):e2356070. doi: 10.1001/jamanetworkopen.2023.56070.
16. Sarzani R, Laureti G, Gezzi A, Spannella F, Giulietti F. Single-pill fixed-dose drug combinations to reduce blood pressure: the right pill for the right patient. Ther Adv Chronic Dis. 2022 Jun;13:20406223221102754. doi: 10.1177/20406223221102754.
17. Kwakye AO, Kretchy IA, Peprah P, Mensah KB. Factors influencing medication adherence in co-morbid hypertension and diabetes patients: a scoping review. Explor Res Clin Soc Pharm. 2024 Feb;13:100426. doi: 10.1016/j.rcsop.2024.100426.
18. Stergiou GS, Palatini P, Parati G, O'Brien E, Januszewicz A, Lurbe E, et al. 2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement. J Hypertens. 2021 Jul;39(7):1293-1302. doi: 10.1097/HJH.0000000000002843.
19. Choi JM, Lee SH, Jang YJ, Kang M, Choi JH. Medication adherence and clinical outcome of fixed-dose combination vs. Free combination of angiotensin receptor blocker and statin. Circ J. 2021 Apr;85(5):595-603. doi: 10.1253/circj.CJ-20-0966.
20. Zhang D, Lee JS, Therrien NL, Pollack LM, Jackson SL, Dong X, et al. Fixed-Dose Combination Use and Drug Adherence, Healthcare Utilization, and Costs. medRxiv. 2024 Nov;2024-11. doi: 10.1101/2024.11.27.24318118.
21. Abushouk AI, Sayed A, Munir M, Ghanem E, Abdelfattah O, Michos ED, et al. Fixed-dose combination (polypill) for cardiovascular disease prevention: a meta-analysis. Am J Prev Med. 2022 Sep;63(3):440-449. doi: 10.1016/j.amepre.2022.03.027.
22. Wang Y, Wang X, Wang X, Naqvi AA, Zhang Q, Zang X. Translation and validation of the Chinese version of the general medication adherence scale (GMAS) in patients with chronic illness. Curr Med Res Opin. 2021 May;37(5):829-837. doi: 10.1080/03007995.2021.1901680.
23. Sung J, Ahn KT, Cho BR, Lee SY, Kim BJ, Kim DK, et al. Adherence to triple-component antihypertensive regimens is higher with single-pill than equivalent two-pill regimens: A randomized controlled trial. Clin Transl Sci. 2021 May;14(3):1185-1192. doi: 10.1111/cts.12979.
24. Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension. 2021 Feb;77(2):692-705. doi: 10.1161/HYPERTENSIONAHA.120.15781.
25. Whelton PK, Carey RM, Mancia G, Kreutz R, Bundy JD, Williams B. Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension blood pressure/hypertension guidelines: comparisons, reflections, and recommendations. Circulation. 2022 Sep;146(11):868-877. doi: 10.1161/CIRCULATIONAHA.121.054602.
26. Dong C, Bu X, Liu J, Wei L, Ma A, Wang T. Cardiovascular disease burden attributable to dietary risk factors from 1990 to 2019: A systematic analysis of the Global Burden of Disease study. Nutr Metab Cardiovasc Dis. 2022 Apr;32(4):897-907. doi: 10.1016/j.numecd.2021.11.012.
27. World Health Organization. The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). World Health Organization; 2023.
28. Chodapuneedi S, Koh JW, Orman Z, Gasevic D, Magliano DJ, Zoungas S, Hamblin P, Trin C, Zomer E, Cataldo P, Talic S. Adherence patterns to cardiovascular medications in people with type 2 diabetes mellitus: a retrospective cohort study using group-based trajectory analysis in primary care. Diabetes Research and Clinical Practice. 2025 Aug 6:112409. doi: 10.1016/j.diabres.2025.112409.
29. Alexander T, Hiremath JS, Swahney JPS, Chandra S, Jain P, Chandra P, et al. Identifying drug prescription in newly diagnosed hypertension patients in India. J Clin Hypertens (Greenwich). 2025 Jan;27(1):e14963. doi: 10.1111/jch.14963.
30. Abbas S, Noor M, Masood AJ, Ahmed E, Shakeel A, Ali MS, et al. Analysis of medication adherence of chronic hypertensive patients in Pakistani community via open survey method. Explor Med. 2024 Oct;5:674–683. doi: 10.37349/emed.2024.00248.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Pakistan Journal of Medicine and Dentistry

This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/