Adverse Drug Reaction of Angiotensin Receptor Blockers (Valsartan, Candesartan, Losartan): a Systematic Review
Abstract
Hypertension is a significant global health problem, with a growing prevalence worldwide. The most commonly documented ADRs of hypertension medication in primary care records include those associated with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). The purpose of this paper is to review and evaluate the potential adverse drug reactions (ADRs) associated with the use of Angiotensin Receptor Blockers (ARBs), specifically valsartan, candesartan, and losartan in the management of hypertension and related diseases. We conducted a systematic review of randomized controlled trial articles that involved valsartan, candesartan, and losartan monotherapy compared with placebo or other standard antihypertensive drugs. PubMed and Google Scholar databases were used in the search for articles in May 2024 and 21 articles were included in this review. This study comprised 21 randomized controlled trials. The study participants' ages ranged from 34.4 years to 76 years. Sample sizes ranged from 16 to 1381 patients with a total 4606 patients. A total of 44 ADRs were observed and the most likely ADRs were headache, dizziness, hypotension, hyperkalemia, nausea, upper respiratory tract infection, and fatigue. Generally, the ADRs that occurred were not fatal and did not lead to discontinuation of therapy. The safety and tolerability profiles of ARBs are among the best for antihypertensive drugs, then overall, the comparison of ARB agents between valsartan, candesartan, and losartan in this class is similar. The most frequent adverse events in the group receiving therapy include headache, dizziness, hypotension, hyperkalemia, nausea, nasopharyngitis, and fatigue.
Keywords
Full Text:
PDFReferences
Iqbal AM, Jamal SF. Essential Hypertension. Treasure Island (FL): StatPearls Publishing; 2024.
Oparil S, Acelajado MC, Bakris GL, et al. Hypertension. Nat Rev Dis Primers. 2018;4(1):18014. doi:10.1038/nrdp.2018.14
Jeemon P, Séverin T, Amodeo C, et al. World Heart Federation Roadmap for Hypertension - A 2021 Update. Glob Heart. 2021;16(1):63. doi:10.5334/gh.1066
Ansar J, Dwinata I. Determinant of Hypertension Incidence among Posbindu Visitor at Work Area of Puskesmas Ballaparang Makassar City. Jurnal Nasional Ilmu Kesehatan. 2019;1(3):28-35.
J H, Andri J, Payana TD, Andrianto MB, Sartika A. Kualitas Tidur Berhubungan dengan Perubahan Tekanan Darah pada Lansia. Jurnal Kesmas Asclepius. 2020;2(1):1-11. doi:10.31539/jka.v2i1.1146
Kementerian Kesehatan RI. Laporan Nasional Riset Kesehatan Dasar (Riskesdas). Badan Penelitian dan Pengembangan Kesehatan; 2018.
Kim JR, Kim S, Huh W, Ko JW. No pharmacokinetic interactions between candesartan and amlodipine following multiple oral administrations in healthy subjects. Drug Des Devel Ther. 2018;Volume 12:2475-2483. doi:10.2147/DDDT.S172568
Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75(6):1334-1357. doi:10.1161/HYPERTENSIONAHA.120.15026
Huang NX, Yuan Q, Fang F, Yan BP, Sanderson JE. Systematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19. PLoS One. 2023;18(1):e0280280. doi:10.1371/journal.pone.0280280
Manzur F, Rico A, Romero JD, Rodriguez-Martinez CE. Efficacy and Safety of Valsartan or Chlorthalidone vs. Combined Valsartan and Chlorthalidone in Patients With Mild to Moderate Hypertension: The VACLOR Study. Clin Med Insights Cardiol. 2018;12:117954681879648. doi:10.1177/1179546818796482
Mujeeb MM. A., Jalikar K. Comparative Efficacy And Safety Of Olmesartan Versus Losartan In Patients With Hypertension. J Evol Med Dent Sci. 2015;4(69):11982-11996. doi:10.14260/jemds/2015/1730
Widyastuti, Noviar, Maizul Putra. Gambaran Penggunaan Obat Antihipertensi di Bangsal Penyakit Dalam RSUD Dr. Achmad Darwis. Jurnal Farmasi Sains dan Obat Tradisional. 2022;1(2):59-70.
Insani WN, Whittlesea C, Ju C, et al. Impact of ACEIs and ARBs-related adverse drug reaction on patients’ clinical outcomes: a cohort study in UK primary care. British Journal of General Practice. 2023;73(736):E832-E842. doi:10.3399/BJGP.2023.0153
Wetmore JB, Yan H, Horne L, Peng Y, Gilbertson DT. Risk of hyperkalemia from renin–angiotensin–aldosterone system inhibitors and factors associated with treatment discontinuities in a real-world population. Nephrology Dialysis Transplantation. 2021;36(5):826-839. doi:10.1093/ndt/gfz263
Brunton LL PKBDBI. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. 11th ed. McGraw-Hill ; 2007.
Aronson JK. Adverse drug reactions – no farewell to harms. Br J Clin Pharmacol. 2007;63(2):131-135. doi:10.1111/j.1365-2125.2006.02860.x
Serban MC, Colantonio LD, Manthripragada AD, et al. Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction. J Am Coll Cardiol. 2017;69(11):1386-1395. doi:10.1016/j.jacc.2016.12.036
Abbasinazari M, Sahraee Z, Mirahmadi M. The Patients’ Adherence and Adverse Drug Reactions (ADRs) which are Caused by Helicobacter pylori Eradication Regimens. J Clin Diagn Res. 2013;7(3):462-466. doi:10.7860/JCDR/2013/4673.2799
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. Published online March 29, 2021:n71. doi:10.1136/bmj.n71
James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. JAMA. 2014;311(5):507. doi:10.1001/jama.2013.284427
De Cassai A, Boscolo A, Zarantonello F, et al. Enhancing study quality assessment: an in-depth review of risk of bias tools for meta-analysis-a comprehensive guide for anesthesiologists. Journal of anesthesia, analgesia and critical care. 2023;3(1):44. doi:10.1186/s44158-023-00129-z
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials. 1996;17(1):1-12. doi:10.1016/0197-2456(95)00134-4
Wang KL, Yu WC, Lu TM, Chen LC, Leu HB, Chiang CE. Amlodipine/valsartan fixed-dose combination treatment in the management of hypertension: A double-blind, randomized trial. Journal of the Chinese Medical Association. 2020;83(10):900-905. doi:10.1097/JCMA.0000000000000386
Shin DH, Song S, Lee YB. Comparison of the Effect of Fimasartan versus Valsartan on Blood Pressure Variability in Acute Ischemic Stroke: A Double-Blind Randomized Trial. Cardiovasc Ther. 2019;2019:1-8. doi:10.1155/2019/7836527
Hajjar I, Okafor M, McDaniel D, et al. Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment. JAMA Netw Open. 2020;3(8):e2012252. doi:10.1001/jamanetworkopen.2020.12252
Lee JH, Yang DH, Hwang JY, et al. A Randomized, Double-blind, Candesartan-controlled, Parallel Group Comparison Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Patients with Mild to Moderate Essential Hypertension. Clin Ther. 2016;38(6):1485-1497. doi:10.1016/j.clinthera.2016.04.005
Kjeldsen SE, Sica D, Haller H, et al. Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results. J Hypertens. 2014;32(12):2488-2498; discussion 2498. doi:10.1097/HJH.0000000000000331
Lai X, Dong Z, Wu S, et al. Efficacy and Safety of Chinese Herbal Medicine Compared with Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial. Circ Cardiovasc Qual Outcomes. 2022;15(3):E007923. doi:10.1161/CIRCOUTCOMES.121.007923
Gismondi RAOC, Oigman W, Bedirian R, Pozzobon CR, Ladeira MCB, Neves MF. Comparison of benazepril and losartan on endothelial function and vascular stiffness in patients with Type 2 diabetes mellitus and hypertension: A randomized controlled trial. J Renin Angiotensin Aldosterone Syst. 2015;16(4):967-974. doi:10.1177/1470320315573681
Maharshi V, Rehan HS, Gupta LK, Yadav M. Comparison of Effect of Enalapril and Losartan Monotherapy on Quality of Life and Safety of Stage 1 Hypertensive Patients. Indian J Physiol Pharmacol. 2016;60(2):174-181.
Park K, Kim Y, Kim K, et al. The impact of a dose of the angiotensin receptor blocker valsartan on post‐myocardial infarction ventricular remodelling. ESC Heart Fail. 2018;5(2):354-363. doi:10.1002/ehf2.12249
Chen CL, Desai-Krieger D, Ortiz S, Kerolous M, Wright HM, Ghahramani P. A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State. Am J Ther. 2015;22(5):e130-40. doi:10.1097/MJT.0000000000000247
Park JB, Shin JH, Kim DS, et al. Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study. Clin Ther. 2016;38(4):832-842. doi:10.1016/j.clinthera.2016.02.025
Fuchs FD, Scala LCN, Vilela-Martin JF, et al. Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial. Acta Diabetol. 2021;58(2):215-220. doi:10.1007/s00592-020-01611-8
Bereda G. Classifying Causality of an Adverse Drug Reaction: Naranjo Algorithm. International Journal of Pharmacy and Chemistry. 2021;7(6):125. doi:10.11648/j.ijpc.20210706.14
Ruggenenti P, Trillini M, P. Barlovic D, et al. Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial. Diabetes Obes Metab. 2019;21(5):1177-1190. doi:10.1111/dom.13639
Ito S, Takahama H, Asakura M, et al. Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial. Sci Rep. 2023;13(1):12517. doi:10.1038/s41598-023-39779-y
McMurray JJ V, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077
Abraham HMA, White CM, White WB. The comparative efficacy and safety of the angiotensin receptor blockers in the management of hypertension and other cardiovascular diseases. Drug Saf. 2015;38(1):33-54. doi:10.1007/s40264-014-0239-7
Caldeira D, David C, Sampaio C. Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2012;12(4):263-277. doi:10.1007/BF03261835
Ruggenenti P, Cortinovis M, Parvanova A, et al. Preventing microalbuminuria with benazepril, valsartan, and benazepril-valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study. PLoS Med. 2021;18(7):e1003691. doi:10.1371/journal.pmed.1003691
Pfeffer MA, McMurray JJ V, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893-1906. doi:10.1056/NEJMoa032292
Escobar J, Rawat A, Maradiaga F, et al. Comparison of Outcomes Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients With Myocardial Infarction: A Meta-Analysis. Cureus. 2023;15(10):e47954. doi:10.7759/cureus.47954
Liang L, Kung JY, Mitchelmore B, Cave A, Banh HL. Comparative peripheral edema for dihydropyridines calcium channel blockers treatment: A systematic review and network meta-analysis. J Clin Hypertens (Greenwich). 2022;24(5):536-554. doi:10.1111/jch.14436
Largeau B, Cracowski J, Lengellé C, Sautenet B, Jonville‐Béra A. Drug‐induced peripheral oedema: An aetiology‐based review. Br J Clin Pharmacol. 2021;87(8):3043-3055. doi:10.1111/bcp.14752
Nugraheni TP, Hidayat L. Resiko Efek Samping Edema terhadap Penggunaan Amlodipin (CCBs) sebagai Antihipertensi: Kajian Literatur. Jurnal Pendidikan Tambusai. 2021;5(3):11347-11352.
Zappe DH, Crikelair N, Kandra A, Palatini P. Time of administration important? Morning versus evening dosing of valsartan. J Hypertens. 2015;33(2):385-392. doi:10.1097/HJH.0000000000000397
Mancia G, Asmar R, Amodeo C, et al. Comparison of single-pill strategies first line in hypertension. J Hypertens. 2015;33(2):401-411. doi:10.1097/HJH.0000000000000409
Takahara M, Shiraiwa T, Shindo M, et al. Efficacy and safety of 10-mg azilsartan compared with 8-mg candesartan cilexetil in Japanese patients with hypertension: a randomized crossover non-inferiority trial. Hypertension Research. 2014;37(9):852-857. doi:10.1038/hr.2014.86
Fukushima S, Oishi M, Aso H, et al. Effects of angiotensin II receptor blockers on serum potassium level and hyperkalemia risk: retrospective single-centre analysis. European Journal of Hospital Pharmacy. 2023;30(4):208-213. doi:10.1136/ejhpharm-2021-002739
Jang BK. Are Angiotensin II Receptor Blockers Really Safe From Aminotransferase Elevation or Drug-Induced Liver Injury? J Korean Med Sci. 2022;37(33). doi:10.3346/jkms.2022.37.e261
Li EC, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database of Systematic Reviews. 2014;2014(8). doi:10.1002/14651858.CD009096.pub2
Bulsara KG, Patel P, Makaryus AN. Candesartan.; 2024.
Aftab RA, Khan AH, Adnan AS, Sulaiman SAS, Khan TM. Efficacy of Losartan in the management of Post-Dialysis Euvolemic Hypertension (HELD-Trial): A Single-Blind Randomized Control Trial. Sci Rep. 2016;6(1):36592. doi:10.1038/srep36592
Aftab R, Khan A, Adnan A, reports SSS, 2017 undefined. Safety and efficacy of losartan 50 mg in reducing blood pressure among patients with post-dialysis euvolemic hypertension: a randomized control trial. nature.com. Accessed June 11, 2024. https://www.nature.com/articles/s41598-017-17437-4
Lai X, Dong Z, Wu S, et al. Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial. Circ Cardiovasc Qual Outcomes. 2022;15(3):e007923. doi:10.1161/CIRCOUTCOMES.121.007923
Gremke N, Kostev K, Kalder M. Association between antihypertensive medication and the risk of urinary tract infection (UTI) of outpatients: a retrospective cohort study. Infection. 2023;51(2):417-424. doi:10.1007/s15010-022-01895-8
Bosch X. Losartan-induced hepatotoxicity. JAMA. 1997;278(19):1572.
Bolotova O, Yoo J, Chaudhri I, et al. Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study. PLoS One. 2020;15(12):e0244708. doi:10.1371/journal.pone.0244708
Mulla S, Patel P, Siddiqui WJ. Losartan. Treasure Island (FL): StatPearls Publishing; 2024.
Vedantam V, Magacha HM, Vedantam N, Dahya V, Abu-Heija U. A Case Report of Losartan Induced Angioedema. Cureus. 2023;15(3):e36525. doi:10.7759/cureus.36525
Dézsi CA. The Different Therapeutic Choices with ARBs. Which One to Give? When? Why? American Journal of Cardiovascular Drugs. 2016;16(4):255-266. doi:10.1007/s40256-016-0165-4
White WB, Cuadra RH, Lloyd E, Bakris GL, Kupfer S. Effects of azilsartan medoxomil compared with olmesartan and valsartan on ambulatory and clinic blood pressure in patients with type 2 diabetes and prediabetes. J Hypertens. 2016;34(4):788-797. doi:10.1097/HJH.0000000000000839
Mancia G, Cha G, Gil-Extremera B, et al. Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial. J Hum Hypertens. 2017;31(3):178-188. doi:10.1038/jhh.2016.54
Aftab RA, Khan AH, Adnan AS, Sulaiman SAS, Khan TM. Safety and Efficacy of Losartan 50 mg in Reducing Blood Pressure among Patients with Post-Dialysis Euvolemic Hypertension: A Randomized Control Trial. Sci Rep. 2017;7(1):17741. doi:10.1038/s41598-017-17437-4
DOI: https://doi.org/10.15416/pcpr.v9i3.56906
Refbacks
- There are currently no refbacks.
