A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension.

Abstract

BACKGROUND:

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).

OBJECTIVE/METHODS:

We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured.

RESULTS:

Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively.

CONCLUSION:

This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.

• Authors: William C Cushman, George L Bakris, William B White, Michael A Weber, Domenic Sica, Andrew Roberts, Eric Lloyd, Stuart Kupfer
• Journal: Journal of hypertension (J Hypertens) Vol. 36 Issue 4 Pg. 947-956 (04 2018) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 29334491 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Antihypertensive Agents
• Benzimidazoles
• Diuretics
• Drug Combinations
• Imidazoles
• Oxadiazoles
• Tetrazoles
• Hydrochlorothiazide
• olmesartan
• azilsartan medoxomil
• Chlorthalidone

Topics

• Aged
• Antihypertensive Agents (administration & dosage)
• Benzimidazoles (administration & dosage)
• Blood Pressure (drug effects)
• Chlorthalidone (administration & dosage)
• Diuretics (administration & dosage)
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Hydrochlorothiazide (administration & dosage)
• Hypertension (drug therapy, physiopathology)
• Imidazoles (administration & dosage)
• Male
• Middle Aged
• Oxadiazoles (administration & dosage)
• Tetrazoles (administration & dosage)