Experience with Azilsartan and Azilsartan Combined with Chlorthalidone in a Preventive Cardiology Center. Fighting the Therapeutic Inertia with a Program Based on Evidence, Personalization, and Empowerment

Main Article Content

Enrique C. Morales-Villegas Luis A. Alcocer-Diaz-Barreiro Gualberto Moreno-Virgen

Abstract

In patients with hypertension (HT), cardiovascular risk reduction is directly proportional to the reduction in blood pressure sustained over time. However, in “real life,” blood pressure control is often insufficient or not sustained over time to achieve optimal cardiovascular risk reduction. In this article, we comment on the multiple reasons which explain this common therapeutic failure.


Also, in this article, we summarize the amazing basic and clinical phase III evidence of azilsartan (AZL) and azilsartan combined with chlortalidone (CLD), two excellent therapeutic options for HT control. With such evidence as scientific background, we communicate our results with almost 300 HT patients treated with azilsartan and azilsartan/chlortalidone in "real life." In brief, our findings were the following:


  1. a) In HT patients with blood pressure (BP) <150/90 mmHg, AZL 40 mg as monotherapy provides practically 100% success to achieve a target BP <140/90 and <130/80 mmHg, in a subpopulation that we have called “hyper-responders”

  2. b) In HT patients with BP <150/90 mmHg (naive or with another treatment failure), AZL/CLD 40/12.5 mg provides practically 100% success to achieve a target BP <140/90 mmHg and 90% to achieve a target BP <130/80 mmHg;

  3. c) In HT patients with BP >150/90 mmHg (generally with another treatment failure), AZL/CLD 80/12.5 mg gives women a success rate greater than 60% to achieve a target BP <140/90 mmHg and greater than 50% to achieve a target BP <130/80 mmHg. The success rates were higher in men, greater than 75% to achieve a target BP <140/90 mmHg and greater than 60% to achieve a target BP <130/80 mmHg. In both cases, the use of amlodipine (2.5, 5, or 10 mg) made it possible to achieve a target BP <140/90 mmHg in 100% of the cases and <130/80 mmHg in 80% of the cases.

Finally, according to our results, we propose a simple three-step strategy based on evidence, personalization, and empowerment which allows reaching a target BP <140/90 mmHg in more than 90% of cases and a target BP <130/80 mmHg in more than 75% of cases in 4 to 12 weeks.

Article Details

How to Cite
MORALES-VILLEGAS, Enrique C.; ALCOCER-DIAZ-BARREIRO, Luis A.; MORENO-VIRGEN, Gualberto. Experience with Azilsartan and Azilsartan Combined with Chlorthalidone in a Preventive Cardiology Center. Fighting the Therapeutic Inertia with a Program Based on Evidence, Personalization, and Empowerment. Medical Research Archives, [S.l.], v. 9, n. 10, oct. 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2555>. Date accessed: 28 nov. 2021. doi: https://doi.org/10.18103/mra.v9i10.2555.
Section
Research Articles

References

1. Whelton PK, Carey RM, Aronow WS, et al. 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. JACC (2017), doi: 10.1016/j.jacc.2017.11.006.
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 (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018; 00:1.98
3. Ojima M, Igata H, Tanaka M et al. In vitro antagonistic properties of a new angiotensin type 1 receptor blocker, Azilsartan, in receptor binding and function studies. J Pharmacol and Exp Ther. 2011; 336:801-808.
4. Kusumoto K, Igata H, Ojima M et al. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. Eur J Pharmacol. 2011; 669:84-93.
5. Iwai M, Imura Y, Horiuchi M. TAK-536, a new AT1 receptor blocker, improves glucose intolerance and adipocyte differentiation. Am J Hypertens. 2007; 20:579-586.
6. Zhao M, Li Y, Wang J, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletzky rats. Diab Obes and Metab. 2011; 13: published online 12 July 2011. Doi.org/10.1111/j.1463-1326.2011. 01471.x
7. Kajiya T, Ho C, Wang J, et al. Molecular and cellular effects of azilsartan: a new generation angiotensin II receptor blocker. J Hypertens. 2011; 29:2476-2483.
8. Naruse M, Koike Y, Kamei N, et al. Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: an open-label randomized clinical trial. PLoS ONE 14(4): e0214727. Doi.org/10.1371/journalpone.021427.
9. White WB, Weber MA, 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; 57:413-420.
10. Sica D, White WB, Weber MA, et al. Comparison of a novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. J Clin Hypertens (Greenwich). 2011; 13:467-472.
11. Bakris GL, 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; 13:81-88.
12. Rakugi H, Enya K, Sugiura K, et al. 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; 35:552-558.
13. Staessen JA, Wang JG, Thijs L, et al. Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until March 2003. J Hypertens. 2003; 21:1055-1076.
14. Carter BL, Ernst M, Cohen JD. Hydrochlorothiazide versus chlortalidone: Evidence supporting their interchangeability. Hypertension. 2004; 43:4-9.
15. Khosla N, Chua DY, Elliot WJ, et al. Are chlortalidone and hydrochlorothiazide equivalent blood-pressure-lowering medications? J Clin Hypertens. 2005; 7:354-356.
16. Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlortalidone on ambulatory and office blood pressure. Hypertension. 2006; 46:352-358.
17. Sica DA. Chlortalidone: Has it always been the best thiazide-type diuretic? Hypertension. 2006; 47:321-322.
18. Flack JM, Sica DA, Nesbitt S. Chlortalidone versus hydrochlorothiazide as the preferred diuretic: Is there a verdict yet? Hypertension. 2011; 57:665-666
19. Kaplan N. Chlortalidone versus hydrochlorothiazide: A tale of tortoises and a hare. Hypertension. 2011; 58:994-995
20. Peterzan MA, Hardy R, Chaturvedi N, et al. Meta-analysis of dose-response relationships for hydrochlorothiazide, chlortalidone, and Bendroflumethiazide on blood pressure, serum potassium and urate. Hypertension. 2012; 59:1104-1109.
21. Weir MR, Agarwal R. Thiazide, and thiazide-like diuretics: Perspectives on individualization of drug and dose based on therapeutic index. Hypertension. 2012; 59:1089-1090.
22. Ernst ME, Neaton JD, Grimm RH, et al. Long-term effects of chlortalidone versus hydrochlorothiazide on electrocardiographic left ventricular hypertrophy in the Multiple Risk Factor Intervention Trial. Hypertension. 2011; 58:1001-1007.
23. MRFIT Research Group. Mortality after 10 ½ years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation. 199; 82:1616-1628.
24. Dorsh MP, Gillespie BW, Erickson SR, et al. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: A retrospective cohort analysis. Hypertension. 2011; 57:689-694.
25. Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: Systematic review and network meta-analysis. Hypertension. 2012; 59:1110-1117.
26. Jennings GLR. Recent clinical trials of hypertension management. Hypertension. 2013; 62:3-7.
27. Engberick RHGO, Frenkel WJ, van den Bogaard B, et al. Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: Systematic review and meta-analysis. Hypertension. 2015; 65:1033-1040.
28. Sica D, Bakris GL, White WB, et al. Blood pressure lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlortalidone: A factorial study. J Clin Hypertens (Greenwich). 2012; 14:284-292.
29. Bakris GL, Sica D, White WB, et al. Antihypertensive efficacy with hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012; 125:1129. e1-1229.e10.
30. Cushman WC, Bakris GL, White WB, et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012; 60:310-318.
31. Takagi H, Misuno Y, Niwa M, et al. A meta-analysis of randomized controlled Trials of azilsartan therapy for blood pressure. Hypertens Res. 2014; 37:432-437.
32. Bakris GL, Zhao L, Kupfer S, et al. Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorotiazide in chronic kidney disease. J Clin Hypertens. 2018:1-9