A randomized titrate-To-Target study comparing fixed-dose combinations of azilsartanmedoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension

William Cushman, George L. Bakris, William B. White, Michael A. Weber, Domenic Sica, Andrew Roberts, Eric Lloyd, Stuart Kupfer

Research output: Contribution to journalArticle

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 20/12.5mg once daily titrated to 40/25mg if needed or AZL-M/CTD 40/12.5mg once daily titrated to 80/25mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5mg FDC once daily titrated to 40/25mg if needed in a randomized, doubleblind, 8-week study of 1085 participants with clinic SBP 160-190mmHg and DBP 119mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/ 90mmHg (≥130/80mmHg 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 165mmHg 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. Keywords: Angiotensin II receptor blocker, antihypertensive therapy, azilsartan medoxomil, chlorthalidone, fixed-dose combination, hypertension, thiazide-like diuretic Abbreviations: ABPM, ambulatory blood pressure monitoring; ANCOVA, analysis of covariance; ARB, angiotensin II receptor blocker; AZL-M, azilsartan medoxomil; AZL-M/CTD, azilsartan medoxomil/ chlorthalidone; CKD, chronic kidney disease; CTD, chlorthalidone; EGFR, estimated glomerular filtration rate; FDC, fixed dose combination; HCTZ, hydrochlorothiazide; OLM, olmesartan medoxomil; OLM/HCTZ, olmesartan medoxomil/hydrochlorothiazide; SPRINT, Systolic Blood Pressure Intervention Trial; UACR, urine albumin-Tocreatinine ratio; ULN, upper limit of normal.

Original languageEnglish (US)
Pages (from-to)947-956
Number of pages10
JournalJournal of Hypertension
Volume36
Issue number4
DOIs
StatePublished - Apr 1 2018

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Chlorthalidone
Hydrochlorothiazide
Hypertension
Angiotensin Receptor Antagonists
Chronic Renal Insufficiency
olmesartan
azilsartan medoxomil
Antihypertensive Agents
Olmesartan Medoxomil
Blood Pressure
Sodium Chloride Symporter Inhibitors
Ambulatory Monitoring
Ambulatory Blood Pressure Monitoring
Glomerular Filtration Rate

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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A randomized titrate-To-Target study comparing fixed-dose combinations of azilsartanmedoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension. / Cushman, William; Bakris, George L.; White, William B.; Weber, Michael A.; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart.

In: Journal of Hypertension, Vol. 36, No. 4, 01.04.2018, p. 947-956.

Research output: Contribution to journalArticle

Cushman, William ; Bakris, George L. ; White, William B. ; Weber, Michael A. ; Sica, Domenic ; Roberts, Andrew ; Lloyd, Eric ; Kupfer, Stuart. / A randomized titrate-To-Target study comparing fixed-dose combinations of azilsartanmedoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension. In: Journal of Hypertension. 2018 ; Vol. 36, No. 4. pp. 947-956.
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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 20/12.5mg once daily titrated to 40/25mg if needed or AZL-M/CTD 40/12.5mg once daily titrated to 80/25mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5mg FDC once daily titrated to 40/25mg if needed in a randomized, doubleblind, 8-week study of 1085 participants with clinic SBP 160-190mmHg and DBP 119mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/ 90mmHg (≥130/80mmHg 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 165mmHg 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. Keywords: Angiotensin II receptor blocker, antihypertensive therapy, azilsartan medoxomil, chlorthalidone, fixed-dose combination, hypertension, thiazide-like diuretic Abbreviations: ABPM, ambulatory blood pressure monitoring; ANCOVA, analysis of covariance; ARB, angiotensin II receptor blocker; AZL-M, azilsartan medoxomil; AZL-M/CTD, azilsartan medoxomil/ chlorthalidone; CKD, chronic kidney disease; CTD, chlorthalidone; EGFR, estimated glomerular filtration rate; FDC, fixed dose combination; HCTZ, hydrochlorothiazide; OLM, olmesartan medoxomil; OLM/HCTZ, olmesartan medoxomil/hydrochlorothiazide; SPRINT, Systolic Blood Pressure Intervention Trial; UACR, urine albumin-Tocreatinine ratio; ULN, upper limit of normal.",
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TY - JOUR

T1 - A randomized titrate-To-Target study comparing fixed-dose combinations of azilsartanmedoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension

AU - Cushman, William

AU - Bakris, George L.

AU - White, William B.

AU - Weber, Michael A.

AU - Sica, Domenic

AU - Roberts, Andrew

AU - Lloyd, Eric

AU - Kupfer, Stuart

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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 20/12.5mg once daily titrated to 40/25mg if needed or AZL-M/CTD 40/12.5mg once daily titrated to 80/25mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5mg FDC once daily titrated to 40/25mg if needed in a randomized, doubleblind, 8-week study of 1085 participants with clinic SBP 160-190mmHg and DBP 119mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/ 90mmHg (≥130/80mmHg 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 165mmHg 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. Keywords: Angiotensin II receptor blocker, antihypertensive therapy, azilsartan medoxomil, chlorthalidone, fixed-dose combination, hypertension, thiazide-like diuretic Abbreviations: ABPM, ambulatory blood pressure monitoring; ANCOVA, analysis of covariance; ARB, angiotensin II receptor blocker; AZL-M, azilsartan medoxomil; AZL-M/CTD, azilsartan medoxomil/ chlorthalidone; CKD, chronic kidney disease; CTD, chlorthalidone; EGFR, estimated glomerular filtration rate; FDC, fixed dose combination; HCTZ, hydrochlorothiazide; OLM, olmesartan medoxomil; OLM/HCTZ, olmesartan medoxomil/hydrochlorothiazide; SPRINT, Systolic Blood Pressure Intervention Trial; UACR, urine albumin-Tocreatinine ratio; ULN, upper limit of normal.

AB - 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 20/12.5mg once daily titrated to 40/25mg if needed or AZL-M/CTD 40/12.5mg once daily titrated to 80/25mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5mg FDC once daily titrated to 40/25mg if needed in a randomized, doubleblind, 8-week study of 1085 participants with clinic SBP 160-190mmHg and DBP 119mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/ 90mmHg (≥130/80mmHg 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 165mmHg 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. Keywords: Angiotensin II receptor blocker, antihypertensive therapy, azilsartan medoxomil, chlorthalidone, fixed-dose combination, hypertension, thiazide-like diuretic Abbreviations: ABPM, ambulatory blood pressure monitoring; ANCOVA, analysis of covariance; ARB, angiotensin II receptor blocker; AZL-M, azilsartan medoxomil; AZL-M/CTD, azilsartan medoxomil/ chlorthalidone; CKD, chronic kidney disease; CTD, chlorthalidone; EGFR, estimated glomerular filtration rate; FDC, fixed dose combination; HCTZ, hydrochlorothiazide; OLM, olmesartan medoxomil; OLM/HCTZ, olmesartan medoxomil/hydrochlorothiazide; SPRINT, Systolic Blood Pressure Intervention Trial; UACR, urine albumin-Tocreatinine ratio; ULN, upper limit of normal.

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