Skip to main content

Newer Angiotensin Receptor Blockers

  • Chapter
  • First Online:
Hypertension and Cardiovascular Disease in Asia

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

  • 762 Accesses

Abstract

Angiotensin receptor blockers (ARBs) are among the most widely used classes of antihypertensive drugs. In addition to their established efficacy and safety, ARBs are well tolerated and have a lower discontinuation rate than any other antihypertensive therapy. To further reduce cardiovascular risk, researchers are looking at multifunctional ARBs with actions beyond just inhibition of the renin–angiotensin system. Some of these additional properties/actions and their implications are discussed in this chapter. These ARBs may have additional actions on their own or may be combined with other molecules to provide further benefit. This has resulted in appearance of some new agents. Two of these, azilsartan and fimasartan, are discussed in detail. Recent studies have also identified newer actions of older agents in this class. Physicians also need to be aware of recalls that apply to some ARB products.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Schmieder RE. Mechanisms for the clinical benefits of angiotensin II receptor blockers. Am J Hypertens. 2005;18(5):720–30.

    Article  CAS  PubMed  Google Scholar 

  2. Castellion AW, Fulton RW. Preclinical pharmacology of saralasin. Kidney Int Suppl. 1979;9:S11–9.

    Google Scholar 

  3. Carey RM, Wang ZQ, Siragy HM. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35(1):155–63.

    Article  CAS  PubMed  Google Scholar 

  4. Pradhan A, Tiwari A, Sethi R. Azilsartan: current evidence and perspectives in management of hypertension. Int J Hypertens. 2019;2019:1824621.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Lee HY, Oh BH. Fimasartan: a new angiotensin receptor blocker. Drugs. 2016;76(10):1015–22.

    Article  CAS  PubMed  Google Scholar 

  6. Klahr S. The role of nitric oxide in hypertension and renal disease progression. Nephrol Dial Transplant. 2001;16(Suppl 1):60–2.

    Article  CAS  PubMed  Google Scholar 

  7. Breschi MC, Calderone V, Digiacomo M, Macchia M, Martelli A, Martinotti E, et al. New NO-releasing pharmacodynamic hybrids of losartan and its active metabolite: design, synthesis, and biopharmacological properties. J Med Chem. 2006;49(8):2628–39.

    Article  CAS  PubMed  Google Scholar 

  8. Breschi MC, Calderone V, Digiacomo M, Martelli A, Martinotti E, Minutolo F, et al. NO-sartans: a new class of pharmacodynamic hybrids as cardiovascular drugs. J Med Chem. 2004;47(23):5597–600.

    Article  CAS  PubMed  Google Scholar 

  9. Li YQ, Ji H, Zhang YH, Shi WB, Meng ZK, Chen XY, et al. WB1106, a novel nitric oxide-releasing derivative of telmisartan, inhibits hypertension and improves glucose metabolism in rats. Eur J Pharmacol. 2007;577(1):100–8.

    Article  CAS  PubMed  Google Scholar 

  10. Trachtman H, Nelson P, Adler S, Campbell KN, Chaudhuri A, Derebail VK, et al. DUET: a phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS. J Am Soc Nephrol. 2018;29(11):2745–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Komers R, Diva U, Inrig JK, Loewen A, Trachtman H, Rote WE. Study design of the phase 3 sparsentan versus irbesartan (DUPLEX) study in patients with focal segmental glomerulosclerosis. Kidney Int Rep. 2020;5(4):494–502.

    Article  PubMed  PubMed Central  Google Scholar 

  12. McMurray JJ. Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances. Eur J Heart Fail. 2015;17(3):242–7.

    Article  CAS  PubMed  Google Scholar 

  13. Jhund PS, McMurray JJ. The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan. Heart. 2016;102(17):1342–7.

    Article  CAS  PubMed  Google Scholar 

  14. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.

    Article  PubMed  CAS  Google Scholar 

  15. Yasar S, Xia J, Yao W, Furberg CD, Xue QL, Mercado CI, et al. Antihypertensive drugs decrease risk of Alzheimer disease: ginkgo evaluation of memory study. Neurology. 2013;81(10):896–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ho JK, Moriarty F, Manly JJ, Larson EB, Evans DA, Rajan KB, et al. Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly: a meta-analysis. Hypertension. 2021;78(3):629–43.

    Article  CAS  PubMed  Google Scholar 

  17. Ho JK, Nation DA. Memory is preserved in older adults taking AT1 receptor blockers. Alzheimers Res Ther. 2017;9(1):1–14.

    Article  Google Scholar 

  18. Angeli F, Verdecchia P, Pascucci C, Poltronieri C, Reboldi G. Pharmacokinetic evaluation and clinical utility of azilsartan medoxomil for the treatment of hypertension. Expert Opin Drug Metab Toxicol. 2013;9(3):379–85.

    Article  CAS  PubMed  Google Scholar 

  19. Kurtz TW, Klein U. Next generation multifunctional angiotensin receptor blockers. Hypertens Res. 2009;32(10):826–34.

    Article  CAS  PubMed  Google Scholar 

  20. Sica D, White WB, Weber MA, Bakris GL, Perez A, Cao C, et al. Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. J Clin Hypertens. 2011;13(7):467–72.

    Article  CAS  Google Scholar 

  21. White WB, Weber MA, Sica D, Bakris GL, Perez A, Cao C, et al. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension. 2011;57(3):413–20.

    Article  CAS  PubMed  Google Scholar 

  22. Gitt AK, Bramlage P, Potthoff SA, Baumgart P, Mahfoud F, Buhck H, et al. Azilsartan compared to ACE inhibitors in anti-hypertensive therapy: one-year outcomes of the observational EARLY registry. BMC Cardiovasc Disord. 2016;16:56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Bönner G, Bakris GL, Sica D, Weber MA, White WB, Perez A, et al. Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril. J Hum Hypertens. 2013;27(8):479–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Chen R, Suchard MA, Krumholz HM, Schuemie MJ, Shea S, Duke J, et al. Comparative first-line effectiveness and safety of ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers: a multinational cohort study. Hypertension. 2021;78(3):591–603.

    Article  CAS  PubMed  Google Scholar 

  25. Bakris GL, Sica D, Weber M, White WB, Roberts A, Perez A, et al. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. J Clin Hypertens. 2011;13(2):81–8.

    Article  CAS  Google Scholar 

  26. Rakugi H, Enya K, Sugiura K, Ikeda Y. Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study. Hypertens Res. 2012;35(5):552–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Takagi H, Mizuno Y, Niwa M, Goto SN, Umemoto T. A meta-analysis of randomized controlled trials of azilsartan therapy for blood pressure reduction. Hypertens Res. 2014;37(5):432–7.

    Article  CAS  PubMed  Google Scholar 

  28. Sinha S, Chary S, Reddy Bandi M, Thakur P, Talluri L, Reddy VK, et al. Evaluation of the efficacy and safety of Azilsartan in adult patients with essential hypertension: a randomized, phase-III clinical study in India. J Assoc Phys. 2021;69(2):35–9.

    Google Scholar 

  29. Kusuyama T, Ogata H, Takeshita H, Kohno H, Shimodozono S, Iida H, et al. Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients. Ther Apher Dial. 2014;18(5):398–403.

    Article  CAS  PubMed  Google Scholar 

  30. Sakamoto M, Asakura M, Nakano A, Kanzaki H, Sugano Y, Amaki M, et al. Azilsartan, but not candesartan improves left ventricular diastolic function in patients with hypertension and heart failure. Int J Gerontol. 2015;9(4):201–5.

    Article  Google Scholar 

  31. Georgiopoulos G, Katsi V, Oikonomou D, Vamvakou G, Koutli E, Laina A, et al. Azilsartan as a potent antihypertensive drug with possible pleiotropic cardiometabolic effects: a review study. Front Pharmacol. 2016;7:235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kajiya T, Ho C, Wang J, Vilardi R, Kurtz TW. Molecular and cellular effects of azilsartan: a new generation angiotensin II receptor blocker. J Hypertens. 2011;29(12):2476–83.

    Article  CAS  PubMed  Google Scholar 

  33. Zhao M, Li Y, Wang J, Ebihara K, Rong X, Hosoda K, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes Obes Metab. 2011;13(12):1123–9.

    Article  CAS  PubMed  Google Scholar 

  34. Iwai M, Chen R, Imura Y, Horiuchi M. TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation. Am J Hypertens. 2007;20(5):579–86.

    Article  CAS  PubMed  Google Scholar 

  35. Park JB, Sung KC, Kang SM, Cho EJ. Safety and efficacy of fimasartan in patients with arterial hypertension (Safe-KanArb study): an open-label observational study. Am J Cardiovasc Drugs. 2013;13(1):47–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cho EJ, Sung KC, Kang SM, Shin MS, Joo SJ, Park JB. Fimasartan reduces clinic and home pulse pressure in elderly hypertensive patients: a K-MetS study. PLoS One. 2019;14(4):e0214293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, et al. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34(3):552–68.

    Article  CAS  PubMed  Google Scholar 

  38. Chung WB, Ihm SH, Jang SW, Her SH, Park CS, Lee JM, et al. Effect of Fimasartan versus valsartan and Olmesartan on office and ambulatory blood pressure in Korean patients with mild-to-moderate essential hypertension: a randomized, double-blind, active control, three-parallel group, forced titration, multicenter, phase IV Study (fimasartan achieving systolic blood pressure target (FAST) study). Drug Des Devel Ther. 2020;14:347–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lee JH, Yang DH, Hwang JY, Hur SH, Cha TJ, Kim KS, 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):1485–97.

    Article  CAS  PubMed  Google Scholar 

  40. Lee HY, Kim YJ, Ahn T, Youn HJ, Chull Chae S, Seog Seo H, et al. A randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design, phase II study to evaluate the efficacy and safety of the combination of fimasartan/amlodipine in patients with essential hypertension. Clin Ther. 2015;37(11):2581–96.

    Article  CAS  PubMed  Google Scholar 

  41. Kim KI, Shin MS, Ihm SH, Youn HJ, Sung KC, Chae SC, et al. A randomized, double-blind, multicenter, phase iii study to evaluate the efficacy and safety of fimasartan/amlodipine combined therapy versus fimasartan monotherapy in patients with essential hypertension unresponsive to fimasartan monotherapy. Clin Ther. 2016;38(10):2159–70.

    Article  CAS  PubMed  Google Scholar 

  42. Rhee MY, Baek SH, Kim W, Park CG, Park SW, Oh BH, et al. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy. Drug Des Devel Ther. 2015;9:2847–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kim JY, Son JW, Park S, Yoo TH, Kim YJ, Ryu DR, et al. Fimasartan proteinuria sustained reduction in comparison with losartan in diabetic chronic kidney disease (FANTASTIC): study protocol for randomized controlled trial. Trials. 2017;18(1):632.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. https://clinicaltrials.gov/ct2/show/NCT03231293. Accessed 24 June 2021.

  45. United States Food and Drug Administration. Search list of recalled angiotensin II receptor blockers (ARBs) including valsartan, losartan and irbesartan. https://www.fda.gov/drugs/drug-safety-and-availability/search-list-recalled-angiotensin-ii-receptor-blockers-arbs-including-valsartan-losartan-and. Accessed July 16, 2019.

  46. United States Food and Drug Administration. Search list of recalled angiotensin II receptor blockers (ARBs) including valsartan, losartan and irbesartan. https://www.fda.gov/drugs/drug-safety-and-availability/search-list-recalled-angiotensin-ii-receptor-blockers-arbs-including-valsartan-losartan-and-FDA. Accessed 28 June 2021.

  47. Health Sciences Authority. Singapore. 2019. https://www.hsa.gov.sg/sartanupdates. Accessed 28 June 2021.

  48. Byrd JB, Chertow GM, Bhalla V. Hypertension hot potato - anatomy of the angiotensin-receptor blocker recalls. N Engl J Med. 2019;380(17):1589–91.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Iyengar, S.S., Saleha, N. (2022). Newer Angiotensin Receptor Blockers. In: Ram, C.V.S., Teo, B.W.J., Wander, G.S. (eds) Hypertension and Cardiovascular Disease in Asia. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-030-95734-6_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-95734-6_23

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-95733-9

  • Online ISBN: 978-3-030-95734-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics