Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease

Abstract

An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability.

Trial registration: ClinicalTrials.gov NCT01309828.

Keywords: cardiovascular; hypertension; kidney; nephropathy; outcomes; renal.

Conflict of interest statement

GLB has received grant or research support from Bayer and is a consultant for AbbVie, Janssen, Bayer, and Merck. LZ, SK, and AJ were employees of Takeda during the time of the study. MH and EL are employees of Takeda Development Center Americas, Inc. GLB was a consultant to Takeda at the time of the study. SO has received research grant support or support/reimbursement for travel to meetings or other from AstraZeneca AB/Duke, Bayer, NIH/NHLBI, NHLBI, NIH/NIAMS, Novartis, Actelion, Rox Medical, Medtronic Ardian, and Merck and has consulted for Actelion, Lundbeck, and Novo Nordisk. SO was an investigator in SPRINT for which Takeda and Arbor Pharmaceuticals donated 5% of medication used.

©2018 Wiley Periodicals, Inc.

Figures

Figure 1

Treatment and titration schedule. aEligible subjects were instructed via the telephone to discontinue their current antihypertensive medications on Days −2 and −1 before they came to the clinic for the Day 1 visit. bEligible subjects who were enrolled in the study were administered study drug in the clinic on Day 1. cEach subject returned to the clinic approximately 2 wk after any dose titration for an unscheduled visit to have vital signs assessed, to undergo a subpanel of clinical laboratory tests (serum creatinine, BUN, chloride, bicarbonate, potassium, and sodium), and to receive study drug. Subjects also returned to the clinic approximately 2 wk after any dose decrease for an unscheduled visit to have vital signs assessed, receive study drug, and repeat clinical laboratory tests, if necessary. The investigator could have requested an unscheduled visit for reasons other than dose titration at any time; the procedures performed at this visit were at the discretion of the investigator. Note: Study drug was titrated according to a titration‐to‐target blood pressure approach

Figure 2

Participant disposition. aSpecific reasons given for discontinuation of study drug were noncompliance with study procedures and blood pressure out of range. bProtocol deviation was related to concomitant medications; subject persistently failed to take add‐on antihypertensive medication per the protocol

Figure 3

Mean (+/SD) systolic and diastolic BP over 52 wk with AZL‐M/CLD vs OLM/HCTZ (observed values)

Figure 4

Mean creatinine and sitting clinic systolic blood pressure value over time by creatinine elevation in all participants: safety analysis set