Efficacy and Safety of Major Antihypertensive Drug Classes in Adults with Hypertension: A Systematic Review
DOI:
https://doi.org/10.22270/ajprd.v14i2.1750Abstract
Background: Hypertension (HTN) remained a major global health concern and a leading risk factor for cardiovascular morbidity and mortality, with many patients requiring more than single-drug therapy to achieve optimal blood pressure control.
Objective: This study aimed to evaluate and compare the efficacy and safety of commonly used antihypertensive drug classes, with a focus on different combination therapy strategies.
Methods: A systematic review was conducted using PubMed and Google Scholar to identify relevant clinical trials and supporting studies in adult patients with HTN. Studies were selected based on predefined eligibility criteria using the Population, Intervention, Comparison, Outcome (PICO) framework. Data extraction included systolic blood pressure (SBP), diastolic blood pressure (DBP), overall blood pressure control, nighttime blood pressure control, sustained effects, and safety outcomes such as adverse effects, electrolyte changes, and heart rate (HR). A structured comparative approach was used to analyze monotherapy, dual therapy, and multi-drug combinations.
Results: The included studies showed that all major antihypertensive drug classes contributed to reductions in SBP and DBP; however, combination therapy demonstrated more consistent and effective overall blood pressure control compared to monotherapy. Differences were observed among drug classes in terms of specific effects, including HR reduction and electrolyte changes.
Conclusion: The findings suggested that combination therapy played an important role in achieving better blood pressure control, and a structured comparison of different drug classes and their combinations provided a clearer understanding of their relative efficacy and safety.
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Zhu D, Bays H, Gao P, Mattheus M, Voelker B, Ruilope LM. Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial. Integr Blood Press Control. 2013;6:1-14. doi:10.2147/IBPC.S33104.
Sung KC, Sung JH, Cho EJ, Ahn JC, Han SH, Kim W, et al. Efficacy and safety of low-dose antihypertensive combination of amlodipine, telmisartan, and chlorthalidone: a randomized, double-blind, parallel, phase II trial. J Clin Hypertens. 2022. doi:10.1111/1750-3841.16020.
Kim SH, Ryu KH, Lee NH, Kang JH, Kim WS, Park SW, et al. Efficacy of fixed-dose amlodipine and losartan combination compared with amlodipine monotherapy in stage 2 hypertension: a randomized, double-blind, multicenter study. BMC Res Notes. 2011;4:461. doi:10.1186/1756-0500-4-461.
Hemminki E, McPherson K. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. BMJ. 1997;315(7101):149-153. doi:10.1136/bmj.315.7101.149.
Higaki J, Komuro I, Shiki K, Ugai H, Taniguchi A, Ikeda H, et al. The efficacy and long-term safety of a triple combination of telmisartan, amlodipine, and hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension. Hypertens Res. 2016. doi:10.1038/hr.2015.142.
Kraiczi H, Hedner J, Peker Y, Grote L. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161(5):1423-1430. doi:10.1164/ajrccm.161.5.9904063.
World Health Organization. WHO guideline for the pharmacological treatment of hypertension in adults. Geneva: World Health Organization; 2021.
Kalra S, Kalra B, Agrawal N. Combination therapy in hypertension: an update. DiabetolMetab Syndr. 2010;2:44. doi:10.1186/1758-5996-2-44.
Magvanjav O, Cooper-DeHoff RM, McDonough CW, Gong Y, Hogan WR, Johnson JA. Combination antihypertensive therapy prescribing and blood pressure control in a real-world setting. Am J Hypertens. 2020;33(11):1047-1055. doi:10.1093/ajh/hpaa093.
Mallat SG, Tanios BY, Itani HS, Akl EA. Free versus fixed combination antihypertensive therapy for essential arterial hypertension: a systematic review and meta-analysis. PLoS One. 2016;11(8):e0161285. doi:10.1371/journal.pone.0161285.
Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Primers. 2018;4:18014. doi:10.1038/nrdp.2018.14.
Wang JG, Kario K, Park JB, Hoshide S, Chen CH, Huo Y, et al. Management of morning hypertension: a consensus statement of an Asian expert panel. J Hypertens. 2018;36(7):1506-1517. doi:10.1097/HJH.0000000000001701.
Pradhan A, Vohra S, Sethi R. A “20/20” match: ACC/AHA 2017 versus ESC/ESH 2018 guidelines for management of hypertension. Indian Heart J. 2019;71(2):151-157. doi:10.1016/j.ihj.2019.03.004.
Memon HA, Park MH. Pulmonary arterial hypertension in women. Methodist Debakey Cardiovasc J. 2017;13(4):224-229. doi:10.14797/mdcj-13-4-224.
Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2015;65(5):1001-1007. doi:10.1161/Hypertensionaha.115.04260.
MacDonald TM, Williams B, Webb DJ, Morant S, Caulfield M, Cruickshank JK, et al. Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial. J Am Heart Assoc. 2017;6(11):e006986. doi:10.1161/JAHA.117.006986.
Guerrero-García C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs Context. 2018;7:212531. doi:10.7573/dic.212531.
Natarajan A, Jose PA. Renal modulation: the renin-angiotensin-aldosterone system (RAAS). In: Comprehensive Clinical Nephrology. Elsevier; 2019.
Takahashi H, Yoshika M, Komiyama Y, Nishimura M. The central mechanism underlying hypertension: roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain. Hypertens Res. 2011;34(11):1147-1152. doi:10.1038/hr.2011.100.
Mallat SG, Itani HS, Tanios BY. Current perspectives on combination therapy in the management of hypertension. Integr Blood Press Control. 2013;6:69-78. doi:10.2147/IBPC.S33940.
Sonobe T, Timilsina RR, Rahut DB. Hypertension among men and women in Asia: a review of the burden and risk factors. Int J Environ Res Public Health. 2019;16(20):3875. doi:10.3390/ijerph16203875.
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension global hypertension practice guidelines. Hypertension. 2020;75(6):1334-1357. doi:10.1161/Hypertensionaha.120.15026.
Garjón J, Saiz LC, Azparren A, Gaminde I, Ariz MJ, Erviti J. First-line combination therapy versus first-line monotherapy for primary hypertension. Cochrane Database Syst Rev. 2020;2:CD010316. doi:10.1002/14651858.CD010316.pub2.
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;77(2):692-705. doi:10.1161/Hypertensionaha.120.15781.
Ott C, Schmieder RE. Diagnosis and treatment of arterial hypertension 2021. Kidney Int. 2021;100(6):1243-1255. doi:10.1016/j.kint.2021.09.026.
Smith DK, Lennon RP, Carlsgaard PB. Managing hypertension using combination therapy. Am Fam Physician. 2020;101(6):341-349.
Molina de Salazar DI, Coca A, Alcocer L, Piskorz D. The rationale for using fixed-dose combination therapy in the management of hypertension in Colombia: a narrative review. Adv Ther. 2024;41(4):1523-1537. doi:10.1007/s40256-024-00634-8.
Messerli FH, Bangalore S, Bavishi C, Rimoldi SF. Angiotensin-converting enzyme inhibitors in hypertension: to use or not to use? J Am Coll Cardiol. 2018;71(13):1474-1482. doi:10.1016/j.jacc.2018.01.058.
Morales-Olivas FJ. Diuretics use in the management of hypertension. Hipertens Riesgo Vasc. 2024;41(2):73-78. doi:10.1016/j.hipert.2024.03.004.
Griffin M, Trow TK. The evolving landscape of combination therapy for pulmonary arterial hypertension. Ther Adv Respir Dis. 2017;11(2):139-153. doi:10.1177/1753465816677485.
Giles TD. Rationale for combination therapy as initial treatment for hypertension. J Clin Hypertens. 2003;5(5):368-374. doi:10.1111/j.1524-6175.2003.02673.x.
Patel PS, Raval AM, Patel AAAK, Patel PDK, Prajapati TG, Patel PB. A comprehensive review of antibiotic resistance: mechanisms, causes, and novel therapeutic approaches. Asian J Pharm Res Dev. 2026;14(2):117-128.
Raval AM, Bhavsar PR, Pandya FU, Patel D. Co-processed excipients in pharmaceutical formulation: advances, characterization, and applications. Asian J Pharm Res Dev. 2026;14(1):105-113. doi:10.22270/ajprd.v14i01.1705.
Patel PBK, Raval AM, Patel HB, Patel KH, Patel P, Vaidya PAK, Kahar KH. A comprehensive review of polycystic ovary syndrome (PCOS): pathophysiology, diagnosis and management. Asian J Pharm Res Dev. 2026;14(2):32-41. doi:10.22270/ajprd.v14i2.1716.
Thakor AD, Dharajiya RM, Shaikh MZ, Raval AM. A review on neuropharmacology: mechanisms, drug classes, and clinical applications. Asian J Pharm Res Dev. 2026;14(1):114-121. doi:10.22270/ajprd.v14i01.1709.
Raval AM, Rana T, Joshi SY, Buch S, Arora B, Patel VS. Artificial intelligence in pharmacy and healthcare: applications in drug discovery, precision medicine, clinical practice, and future perspectives. Asian J Pharm Res Dev. 2026;14(2):62-69. doi:10.22270/ajprd.v14i2.1721.
Senjaliya T, Patel M, Raval AM. Strategies for combating the global health threat of antibiotic resistance: novel therapeutics and combination approaches. Asian J Pharm Res Dev. 2026;14(1):122-130. doi:10.22270/ajprd.v14i01.1707.
Mevada J, Patel K, Raval AM. Materiovigilance: From device failure to safety reform, the growing importance of materiovigilance systems. Int J Pharm Sci. 2026;4(1):962-74.
Falwariya R, Jethva T, Raval AM, Lokhande D. Comprehensive review: Microneedle patches–A painless revolution in transdermal drug delivery. World J Pharm Med Res. 2026;12(1):199-207.
Mevada J, Patel K, Raval AM. Role of pharmacovigilance in drug safety monitoring. World J Pharm Med Res. 2025;11(11):235-40.
Patel N, Raval AM. Gastro-retentive drug delivery system: A review. Int J Pharm Sci. 2026;4(1):734-42.
Zankhwala MF, Raval MA, Kushkiwala MA, Sarvaiya MS, Raval MK, Thakar MN, Barjod MS. Formulation And Evaluation Of Optimized Polymer Blends For Diclofenac Diethylamine Transdermal System. The Review of Diabetic Studies. 2025 Sep 14:701-8.
Kushkiwala AM, Zankhwala FM, Patel MD, Raval AM. Flurbiprofen loaded ethosomal gel: Design, optimization, and anti-inflammatory activity. Int J Res Anal Rev. 2024;11(4):709-42.
Raval MA, Suthar MA, Durani MB, Thakar MN, Zankhwala MF, Kushkiwala MA, Rathod MS. Smart Co-Processed Excipient Platforms: A Novel Strategy for Multifunctional Optimization of Ibuprofen Tablet Formulations. practice.;1:2.
Tripathi KD. Essentials of medical pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2019.
Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Antihypertensive drugs. In: Rang and Dale’s pharmacology. 10th ed. London: Elsevier; 2023.
Raval AM, Zankhwala FS. Disease & treatment (बीमारियांऔरउनकाउपचार).Testbook Edu Solutions Pvt Ltd; 2023. ISBN: 978-81-966977-7-8
Raval AM, Rathod SR. Medicine review. Raval Amarkumar Maheshbhai; 2026. ISBN: 978-93-5890-644-8
Dimmitt SB, Stampfer HG, Martin JH, Ferner RE. Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50. Br J Clin Pharmacol. 2019;85(10):2218-2227. doi:10.1111/bcp.14033.
Jussil H, Chaimani A, Carlberg B, et al. Comparative efficacy and acceptability of different antihypertensive drug classes for cardiovascular disease prevention: protocol for a systematic review and network meta-analysis. BMJ Open. 2021;11:e044302. doi:10.1136/bmjopen-2020-044302.
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