Efficacy and tolerability of azilsartan combined with amlodipine and amlodipine monotherapy and combinations of amlodipine with other angiotensin II receptor blockers

Close metadata

OBJECTIVE

To evaluate the efficacy and safety of combining various angiotensin II receptor blockers with amlodipine compared with amlodipine alone, as well as intake of azilsartan 20—80 mg daily and amlodipine 5—10 mg daily compared to other angiotensin II receptor blockers combined with amlodipine in patients with hypertension.

MATERIAL AND METHODS

The review enrolled 22 clinical trials (21 RCTs and 1 observational study) and 9.708 patients. Among 21 RCTs, 19 studies were blinded and 2 RCTs were open-label.

RESULTS

We found more significant SBP decrease in case of combination of azilsartan with amlodipine compared to amlodipine alone (5 or 10 mg daily). Such advantages of combined antihypertensive therapy with azilsartan and amlodipine were more pronounced compared to combination of other ARBs with amlodipine. Moreover, these advantages of azilsartan combined with amlodipine were significantly clearer compared to valsartan or losartan.

CONCLUSION

We found higher antihypertensive efficacy of azilsartan combined with amlodipine in comparison with combination of other ARBs and amlodipine monotherapy. Despite higher antihypertensive efficacy of azilsartan combined with amlodipine, safety of this therapy did not differ from combination of other ARBs with amlodipine or amlodipine monotherapy.

Keywords:

arterial hypertension

systolic blood pressure

angiotensin II receptor blockers

azilsartan

network meta-analysis

Authors:

Gilyarevsky S.R.

Russian Gerontology Research Clinical Center

ORCID: 0000-0002-8505-1848

Karpov Yu.A.

National Medical Research Center for Cardiology

ORCID: 0000-0003-1480-0458

Luchnikova E.A.

Sciencefiles LLC

ORCID: 0009-0009-2030-7185

Lantsova E.V.

Sciencefiles LLC

ORCID: 0000-0002-1412-0711

Received:

05.11.2024

Accepted:

11.11.2024

List of references:

McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, Christodorescu RM, Daskalopoulou SS, Ferro CJ, Gerdts E, Hanssen H, Harris J, Lauder L, McManus RJ, Molloy GJ, Rahimi K, Regitz-Zagrosek V, Rossi GP, Sandset EC, Scheenaerts B., Staessen JA, Uchmanowicz I, Volterrani M., Touyz RM. ESC Scientific Document Group. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024 Aug 30:ehae178. https://doi.org/10.1093/eurheartj/ehae178
https://doi.org/10.15829/1560-4071-2024-6117 https://doi.org/10.15829/1560-4071-2024-6117.EDN:GUEWLU
Yang R, Tang J, Kuang M, Liu H. Analysis of prescription status of antihypertensive drugs in Chinese patients with hypertension based on real-world study. Ann Med. 2023;55(1):276-284. https://doi.org/10.1080/07853890.2022.2162113
Mann JFE, Flack J.M. Choice of drug therapy in primary (essential) hypertension (Literature review current through: Sep 2024). Available at: www.uptodate.com/contents/choice-of-drug-therapy-in-primary-essential-hypertension#disclaimerContent.
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte A.E. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75(6):1334-1357. https://doi.org/10.1161/HYPERTENSIONAHA.120.15026
Schmieder RE, Wassmann S, Predel HG, Weisser B, Blettenberg J, Gillessen A, Randerath O, Mevius A, Wilke T, Böhm M. Improved Persistence to Medication, Decreased Cardiovascular Events and Reduced All-Cause Mortality in Hypertensive Patients With Use of Single-Pill Combinations: Results From the START-Study. Hypertension. 2023;80(5):1127-1135. https://doi.org/10.1161/HYPERTENSIONAHA.122.20810
Shim SR, Kim SJ, Lee J, Rücker G. Network meta-analysis: application and practice using R software. Epidemiol Health. 2019;41:e2019013. https://doi.org/10.4178/epih.e2019013
Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785-1805. https://doi.org/10.1177/0962280216669183
Shi J, Luo D, Weng H, Zeng XT, Lin L, Chu H, Tong T. Optimally estimating the sample standard deviation from the five-number summary. Res Synth Methods. 2020;11(5):641-654. https://doi.org/10.1002/jrsm.1429
Cochrane Handbook for Systematic Reviews of Interventions. Available at: training.cochrane.org/handbook/current.
Higgins JPT, Green S, Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Chichester, England ; Hoboken, NJ: Wiley-Blackwell; 2008. 649 с. (Cochrane book series).
Risk of bias tools — robvis (visualization tool). Available at: sites.google.com/site/riskofbiastool/welcome/robvis-visualization-tool.
Smith AP, Overton K, Rakotz M, Wozniak G, Sanchez E. Target: BP™: A National Initiative to Improve Blood Pressure Control. Hypertension. 2023 Dec;80(12):2523-2532. https://doi.org/10.1161/HYPERTENSIONAHA.123.20389
Bakris GL, Weber MA. Overview of the Evolution of Hypertension: From Ancient Chinese Emperors to Today. Hypertension. 2024;81(4):717-726. https://doi.org/10.1161/HYPERTENSIONAHA.124.21953
Makani H, Bangalore S, Supariwala A, Romero J, Argulian E, Messerli F.H. Antihypertensive efficacy of angiotensin receptor blockers as monotherapy as evaluated by ambulatory blood pressure monitoring: a meta-analysis. Eur Heart J. 2014;35(26):1732-1742. https://doi.org/10.1093/eurheartj/eht333
https://doi.org/10.18087/cardio.2024.4.n2646 https://doi.org/10.18087/cardio.2024.4.n2646
Wang JG, Zhang M, Feng YQ, Ma CS, Wang TD, Zhu ZM, Kario K. Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis. J Clin Hypertens (Greenwich). 2021 May;23(5):901-914. https://doi.org/10.1111/jch.14227
Bobrie G.; I-COMBINE Study Investigators. I-COMBINE study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study. Clin Ther. 2012;34(8):1705-1719. https://doi.org/10.1016/j.clinthera.2012.06.026
Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther. 2008;30(4):587-604. https://doi.org/10.1016/j.clinthera.2008.04.002
Flack JM, Calhoun DA, Satlin L, Barbier M, Hilkert R, Brunel P. Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study. J Hum Hypertens. 2009;23(7):479-89. https://doi.org/10.1038/jhh.2008.153
Kang SM, Youn JC, Chae SC, Park CG, Yang JY, Kim MH, Hong TJ, Kim CH, Kim JJ, Shin DG, Jeong JW, Yoon JH, Park SH, Kwon J, Cho SY. Comparative efficacy and safety profile of amlodipine 5 mg/losartan 50 mg fixed-dose combination and amlodipine 10 mg monotherapy in hypertensive patients who respond poorly to amlodipine 5 mg monotherapy: an 8-week, multicenter, randomized, double-blind phase III noninferiority study. Clin Ther. 2011;33(12):1953—1963. https://doi.org/10.1016/j.clinthera.2011.11.007
Ke Y, Zhu D, Hong H, Zhu J, Wang R, Cardenas P, Zhang Y. Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy. Curr Med Res Opin. 2010;26(7):1705-13. https://doi.org/10.1185/03007995.2010.487391
Lin TH, Tsai CD, Pan JP, Hou CJ, Hsia CH, Tsai JP, Lai W.T. Efficacy and tolerability between an olmesartan/amlodipine fixed-dose combination and an amlodipine double dose in mild to moderate hypertension. Kaohsiung J Med Sci. 2013;29(5):265-70. https://doi.org/10.1016/j.kjms.2012.09.005
Littlejohn T.W. 3rd, Majul CR, Olvera R, Seeber M, Kobe M, Guthrie R, Oigman W.; Study Investigators. Results of treatment with telmisartan-amlodipine in hypertensive patients. J Clin Hypertens (Greenwich). 2009; 11(4):207-213. https://doi.org/10.1111/j.1751-7176.2009.00098.x
Efficacy and Safety of Valsartan and Amlodipine in Patients With Essential Hypertension | ClinicalTrials.gov Available at :clinicaltrials.gov/study/NCT00425373.
Blood Pressure Lowering Ability and Safety of an Olmesartan and Amlodipine Based Treatment Regimen in Patients With Stage I and Stage II Hypertension | ClinicalTrials.gov Availabe at: clinicaltrials.gov/study/NCT00527514?intr=olmesartan%20amlodipine&rank=6&aggFilters=results:with.
Filtered Trial for Amlodipine Non-responder. Availabe at: clinicaltrials.gov/study/NCT00558064?intr=telmisartan%20amlodipine&rank=9&aggFilters=results:with
Telmisartan/Amlodipine (80/5) vs. Telmisartan/Amlodipine (40/5) vs. Amlodipine 10 or 5 in Resistant Hypertension. Availabe at: https://clinicaltrials.gov/study/NCT00558428?intr=telmisartan%20amlodipine&rank=17&aggFilters=results:with&page=2
Safety, Tolerability, and Efficacy of Once Daily Amlodipine/Valsartan 5/80 as Compared to Amlodipine/Valsartan 5/40 or to Amlodipine 5 mg Monotherapy in Patients 65 Years of Age and Older With Essential Hypertension. Availabe at: clinicaltrials.gov/study/NCT00699192?tab=results
Park CG, Youn HJ, Chae SC, Yang JY, Kim MH, Hong TJ, Kim CH, Kim JJ, Hong BK, Jeong JW, Park SH, Kwan J, Choi YJ, Cho S.Y. Evaluation of the dose-response relationship of amlodipine and losartan combination in patients with essential hypertension: an 8-week, randomized, double-blind, factorial, phase II, multicenter study. Am J Cardiovasc Drugs. 2012;12(1):35-47. https://doi.org/10.2165/11597170-000000000-00000
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):563-580. https://doi.org/10.1016/j.clinthera.2007.03.018
Rakugi H, Ogihara T, Miyata Y, Sasai K, Totsuka N. Evaluation of the efficacy and tolerability of combination therapy with candesartan cilexetil and amlodipine besilate compared with candesartan cilexetil monotherapy and amlodipine besilate monotherapy in Japanese patients with mild-to-moderate essential hypertension: a multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2012;34(4):838-848. https://doi.org/10.1016/j.clinthera.2012.02.015
Rakugi H, Nakata E, Sasaki E, Kagawa T. Evaluation of the efficacy and tolerability of fixed-dose combination therapy of azilsartan and amlodipine besylate in Japanese patients with grade I to II essential hypertension. Clin Ther. 2014;36(5):711-721. https://doi.org/10.1016/j.clinthera.2014.03.009
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 Feb;63(2):217-25. PMID: 19196360; PMCID: PMC2705817. https://doi.org/10.1111/j.1742-1241.2008.01977.x
Sharma AM, Bakris G, Neutel JM, Littlejohn TW, Kobe M, Ting N, Ley L. Single-pill combination of telmisartan/amlodipine versus amlodipine monotherapy in diabetic hypertensive patients: an 8-week randomized, parallel-group, double-blind trial. Clin Ther. 2012;34(3):537-51. https://doi.org/10.1016/j.clinthera.2012.02.004
Sohn IS, Kim CJ, Ahn T, Youn HJ, Jeon HK, Ihm SH, Cho EJ, Chung WB, Chae SC, Kim WS, Nam CW, Park SM, Choi JY, Kim YK, Hong TJ, Lee HY, Cho JH, Shin ES, Yoon JH, Yang TH, Jeong MH, Lee JH, Park JI. Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial. Clin Ther. 2017;39(8):1628-1638. https://doi.org/10.1016/j.clinthera.2017.06.014
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. https://doi.org/10.2165/0044011-200929010-00002
Weber MA, White WB, Sica D, Bakris GL, Cao C, Roberts A, Kupfer S. Effects of combining azilsartan medoxomil with amlodipine in patients with stage 2 hypertension. Blood Press Monit. 2014;19(2):90-97. https://doi.org/10.1097/MBP.0000000000000027
Zhu JR, Zhang SY, Gao P.J. Efficacy and safety of olmesartan medoxomil/amlodipine fixed-dose combination for hypertensive patients uncontrolled with monotherapy. Arch Pharm Res. 2014;37(12):1588-1598. https://doi.org/10.1007/s12272-014-0446-x

Close metadata