Azilsartan medoxomil/chlorthalidone – a new effective antihypertensive combination
AbstractArterial hypertension is one of the most common cardiovascular pathology, the incidence of which is steadily increasing. A practicing physician should keep in mind that a blood pressure increasement is a risk factor for a large number of cardiovascular diseases and catastrophes. Currently, the clinical recommendations of most cardiological communities adhere to the position of initiating antihypertensive therapy with a combination of two different classes drugs included in one tablet.
Aim of this review is to analyze data from clinical trials and asses the efficiency and safety of the combined antihypertensive drug azilsartan medoxomil/chlorthaldone and its components.
Material and methods. For this review, a literature search was conducted with the usage of PudMed, MEDLINE, EMBASE, Cochrane Library and the keywords and MeSH terms “azilsartan“, “azilsartan medoxomil“, “chlorthalidone“, “thiazide“, “safety“, “tolerance“, “blood pressure“ and “hypertension“. References for retrieved articles were also scanned for relevant citations. 54 clinical trials and reviews involving azilsartan medoxomil/chlorthalidone or each component individually for the treatment of hypertension were reviewed.
Results. According to the data obtained from 54 articles and reviews that fully meet the objectives of the study, both individual components as well as the combination of azilsartan medoxomil/chlorthalidone have demonstrated their effectiveness and safety when used as part of antihypertensive therapy
Conclusion. According to the randomized intra- and infragroup trials azilsartan medoxomil demonstrated an advantage over candesartan, telmisartan, olmesartan, valsartan and ramipril in the effectiveness of lowering blood pressure. Chlorthalidone showed similar results when it was compared with hydrochlorothiazide. The combination of azilsartan medoxomil/chlorthalidone has demonstrated safety and efficacy in lowering BP in hypertensive patients to a greater degree than olmesartan medoxomil/hydrochlorothiazide and azilsartan medoxomil/hydrochlorothiazide. As a fixed-dose combination tablet, it offers several clinical advantages.
Keywords:arterial hypertension; life quality; Edarbi®; azilsartan medoxomil/chlorthalidone
Funding. The article was prepared with the support of JSC “Nizhpharm” (group of companies STADA).
For citation: Serezhina E.K., Obrezan A.G. Azilsartan medoxomil/chlorthalidone – a new effective antihypertensive combination. Kardiologiya: novosti, mneniya, obuchenie [Cardiology: News, Opinions, Training]. 2022; 10 (3): 16–25. DOI: https://doi.org/10.33029/2309-1908-2022-10-3-16-25 (in Russian)
References
1. URL: https://www.who.int/news-room/fact-sheets/detail/hypertension
2. Williams B., Mancia G., Spiering W., et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Journal of Hypertension. 2018. 36 (10): 1953–2041. DOI: https://www.doi.org/10.1097/HJH.0000000000001940
3. American Heart Association Task Force on Clinical Practice Guidelines. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology. Circulation. 2020. 141 (16): e774.
4. Yan R., Gu H.Q., Wang W., et al. Health-related quality of life in blood pressure control and blood lipid-lowering therapies: results from the CHIEF randomized controlled trial // Hypertens Res. 2019; (42): 1561–71.
5. Grimm R.H. Jr., Grandits G.A., Cutler J.A., Stewart A.L., et al. Relationships of quality-of-life measures to long-term lifestyle and drug treatment in Treatment of Mild Hypertension Study. Arch Intern Med. 1997; 157: 638–48.
6. Wiklund I., Halling K., Ryden-Bergsten T., Fletcher A. Does lowering the blood pressure improve the mood? Quality-of-life results from the Hypertension Optimal Treatment (HOT) study. Blood Press. 1997; (6): 357–64.
7. Plaisted C.S., Lin P.H., Ard J.D., McClure M.L., Svetkey L.P. The effects of dietary patterns on quality of life: a substudy of the Dietary Approaches to Stop Hypertension trial. J Am Diet Assoc. 1999; (99): 84–9.
8. Degl’Innocenti A., Elmfeldt D., Hofman A., Lithell H., et al. Health-related quality of life during treatment of elderly patients with hypertension: results from the Study on COgnition and Prognosis in the Elderly (SCOPE). J Hum Hypertens. 2004; (18): 239–45.
9. Arija V., Villalobos F., Pedret R., Vinuesa A., et al. Physical activity, cardiovascular health, quality of life and blood pressure control in hypertensive subjects: randomized clinical trial. Health Qual Life Outcomes. 2018; 16 (1): 184.
10. Uchmanowicz B., Chudiak A., Mazur G. The influence of quality of life on the level of adherence to therapeutic recommendations among elderly hypertensive patients. Patient Prefer Adherence. 2018; (12): 2593–603.
11. Katsi V., Michalakeas C., Soulaidopoulos S., Antonopoulos A.S., Vlachopoulos C., Tousoulis D., Tsioufis K. Evaluating the safety and tolerability of azilsartan medoxomil alone or in combination with chlorthalidone in the management of hypertension: a systematic review. Curr Hypertens Rev. 2021; 17 (3): 217–27. DOI: https://www.doi.org/10.2174/1573402117666210112144505
12. Brook R.D., Rajagopalan S. 2017 ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Soc Hypertens. 2018; 12: 238.
13. 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: 552–8.
14. Rakugi H., Kario K., Enya K., Sugiura K., Ikeda Y. Effect of azilsartan versus candesartan on morning blood pressure surges in Japanese patients with essential hypertension. Blood Press Monit. 2014; 19: 164–9.
15. Perez A., Cao C. Azilsartan in patients with mild to moderate hypertension using clinic and ambulatory blood pressure measurements. J Clin Hypertens (Greenwich). 2017; 19: 82–9.
16. Perez A., Cao C. The impact of azilsartan medoxomil treatment (capsule formulation) at doses ranging from 10 to 80 mg: significant, rapid reductions in clinic diastolic and systolic blood pressure. J Clin Hypertens (Greenwich). 2017; 19: 312–21.
17. Bakris G.L., Sica D., Weber M., et al. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. J Clin Hypertens (Greenwich). 2011; 13: 81–8.
18. Sica D., White W.B., Weber M.A., et al. Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. J Clin Hypertens 2011; 13: 467–72.
19. White W.B., Cuadra R.H., Lloyd E., et al. 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): 788–97.
20. Okamura K., Shirai K., Okuda T., Urata H. Improvement of diurnal blood pressure variation by azilsartan. J Clin Med Res. 2018; 10: 41–9.
21. White W.B., Weber M.A., Sica D., 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: 413–20.
22. Wang J.G., Zhang M., Feng Y.Q., Ma C.S., Wang T.D., Zhu Z.M., 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; 23 (5): 901–14.
23. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42 (36): 3599–726.
24. Bönner G., Bakris G.L., Sica D., et al. Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril. J Hum Hypertens. 2013; 27: 479–86.
25. Gitt A.K., Bramlage P., Potthoff S.A., 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.
26. Bakris G.L., Sica D., White W.B., et al. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012; 125 (12): 1229.e1-1229.e10.
27. Duarte J.D., Cooper-DeHoff R.M. Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics. Expert Rev Cardiovasc Ther. 2010; 8: 793–802.
28. van Brummelen P., Man in ‘t Veld A.J., Schalekamp M.A. Hemodynamic changes during long-term thiazide treatment of essential hypertension in responders and nonresponders. Clin Pharmacol Ther. 1980; 27: 328–36.
29. Tamargo J., Segura J., Ruilope L.M. Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics. Expert Opin Pharmacother. 2014; 15 (4): 527–47. DOI: https://www.doi.org/10.1517/14656566.2014.879118
30. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288: 2981–97.
31. Liebson P.R., Grandits G.A., Dianzumba S., Prineas R.J., Grimm R.H. Jr, Neaton J.D., Stamler J. Comparison of five antihypertensive monotherapies and placebo for change in left ventricular mass in patients receiving nutritional-hygienic therapy in the Treatment of Mild Hypertension Study (TOMHS). Circulation. 1995; 91 (3): 698–706. DOI: https://www.doi.org/10.1161/01.cir.91.3.698. PMID: 7828296.
32. Gottdiener J.S., Reda D.J., Williams D.W., Materson B.J. et al. Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents. Circulation. 1998; 98 (2): 140–8.
33. Rakić D., Rumboldt Z., Bagatin J., Polić S. Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study. Croat Med J. 2002; 43 (6): 672–9.
34. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991;265: 3255e3264.
35. Anonymous. JAMA. 1967; 202: 1028–34.
36. Multiple Risk Factor Intervention Trial Research Group. Circulation. 1990; 82: 1616–28.
37. Wilhelmsen L., Berglund G., Elmfeldt D., Fitzsimons T., Holzgreve H., Hosie J., Hörnkvist P.E., Pennert K., Tuomilehto J., Wedel H. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J Hypertens. 1987; 5 (5): 561–72.
38. PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chin Med J (Engl). 1995; 108 (9): 710–7.
39. Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979; 242 (23): 2562–71.
40. Roush G.C., Ernst M.E., Kostis J.B., Tandon S., Sica D.A. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015; 65: 1041–6.
41. Lund B.C., Ernst M.E. The comparative effectiveness of hydrochlorothiazide and chlorthalidone in an observational cohort of veterans. J Clin Hypertension (Greenwich). 2012; 14: 623–9.
42. Peterzan M.A., Hardy R., Chaturvedi N., Hughes A.D. Meta-analysis of doseresponse relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension. 2012; 59: 1104–9.
43. Hulley S.B., Furberg C.D., Gurland B., et al. Systolic hypertension in the elderly Program (SHEP): antihypertensive efficacy of chlorthalidone. Am J Cardiol. 1985; 56: 913–20.
44. Ernst M.E., Carter B.L., Goerdt C.J., et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006; 47 (3): 352–8.
45. Bakris G.L., Zhao L., Kupfer S., et al. Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease. J Clin Hypertens (Greenwich). 2018; 20: 694–702.
46. Cushman W.C., Bakris G.L., White W.B., et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012; 60: 310–8.
47. Jin C., O’Boyle S., Kleven D.T., Pollock J.S., Pollock D. M., White J.J. Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet. Clinical and Experimental Pharmacology and Physiology. 2014; 41 (8): 579–88. DOI: https://www.doi.org/10.1111/1440-1681.12250
48. Khan A.H., Neckář J., Haines J., Imig J.D. Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats. American Journal of Hypertension. 2014; 27 (8): 1087–95. DOI: https://doi.org/10.1093/ajh/hpu016
49. Calhoun D.A., Jones D., Textor S., et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American heart association professional education committee of the council for high blood pressure research. Hypertension. 2008; 51: 1403–19.
50. Sheppard J.P., Martin U., McManus R.J. Diagnosis and management of resistant hypertension. Heart. 2017; 103: 1295–302.
51. Shuster J.E., Bleske B.E., Dorsch M.P. Clinical utility of azilsartanchlorthalidone fixed combination in the management of hypertension. Vasc Health Risk Manag. 2012; 8: 381–7.