Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial

Abstract

Background: We conducted this study to examine the effect of taking versus holding BP medications before hemodialysis on intradialytic hypotension (IDH).

Methods: In this cluster randomized trial, each dialysis unit was randomly designated as TAKE or HOLD units. Participants within a TAKE unit were instructed to take all BP medications as prescribed, whereas participants within a HOLD unit were instructed to hold medications dosed more than once daily before hemodialysis. The intervention lasted for 4 weeks. We hypothesized that TAKE would be noninferior to HOLD on the primary outcome of asymptomatic IDH, defined as ≥30% of sessions with nadir systolic BP <90 mm Hg and on the following secondary outcomes: uncontrolled hypertension (predialysis systolic BP >160 mm Hg), failure to achieve dry weight, and shortened dialysis sessions.

Results: We randomized 10 dialysis units in a 1:1 ratio to TAKE or HOLD, which included 65 participants in TAKE and 66 participants in HOLD. We did not show that TAKE was noninferior to HOLD for the primary IDH outcome (mean unadjusted difference of 8%; 95% CI, -3% to 19%). TAKE was superior to HOLD for the outcome of uncontrolled hypertension (mean unadjusted difference of -15%, 95% CI, -28% to -1%). TAKE was noninferior to HOLD for the outcomes of failure to achieve dry weight and shortened dialysis sessions.

Conclusions: In this cluster randomized trial that randomized patients to either taking or holding BP medications before hemodialysis, a strategy of taking BP medications dosed more than once daily was not noninferior to holding BP medications for the primary outcome of IDH, but did reduce the occurrence of uncontrolled hypertension. Whether any potential benefit of holding BP medications on reducing IDH is offset by any potential harm related to higher predialysis BP remains to be seen.

Trial registration: ClinicalTrials.gov NCT03327909.

Keywords: blood pressure; clinical trial; dialysis; end stage kidney disease; hemodialysis.

Conflict of interest statement

G.M. Chertow reports serving on the Board of Directors for Satellite Healthcare, a nonprofit dialysis provider; reports serving as a consultant to Akebia, Ardelyx, AstraZeneca, Baxter, CloudCath, Cricket, Durect, Gilead, Miromatrix, Outset, Reata, Sanifit, and Vertex; and reports serving on data safety monitoring boards for Angion, Bayer, National Institute of Diabetes and Digestive and Kidney Diseases, and ReCor. T.I. Chang reports receiving funding from Janssen Pharmaceuticals to Stanford University for serving as a national leader for CREDENCE; and reports serving as a consultant for AstraZeneca, Bayer, Fresenius Medical Care, Gilead, Janssen Pharmaceuticals, Novo Nordisk, and Tricida. All remaining authors have nothing to disclose.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Dialysis unit and participant flow diagram for the Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis study.

Figure 2.

Effect of TAKE versus HOLD on the specified outcomes, defined as the proportion of participants with ≥30% of sessions with that outcome during the 4-week intervention period. Adjusted values include the baseline proportion of the specified outcomes in the models. 95% CI, 95% confidence interval.