Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study)

PLoS One. 2015 Jun 1;10(6):e0126882. doi: 10.1371/journal.pone.0126882. eCollection 2015.

Abstract

Background and aim: Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan.

Design: Randomized, double-blind, placebo-controlled, one-year intervention trial.

Setting and participants: Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.

Intervention: Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients.

Outcomes and measurements: Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.

Results: At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters.

Conclusion: Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen.

Trial registration: Clinicaltrials.gov NCT00791830.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Biphenyl Compounds / pharmacology*
  • Blood Pressure / drug effects
  • Double-Blind Method
  • Female
  • Hemodynamics / drug effects*
  • Humans
  • Hypotension / drug therapy
  • Hypotension / physiopathology
  • Irbesartan
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Placebos
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Renal Dialysis*
  • Tetrazoles / pharmacology*
  • Time Factors

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Placebos
  • Receptor, Angiotensin, Type 2
  • Tetrazoles
  • Irbesartan

Associated data

  • ClinicalTrials.gov/NCT00791830

Grants and funding

The SAFIR study was primarily supported by The Danish Council for Independent Research Medical Sciences, but also by (in alphabetical order): Aase og Ejnar Danielsens Fond, Beckett-Fonden, Civilingeniør Frode Nygaard og Hustrus Fond, The Danish Society of Hypertension, The Danish Society of Nephrology, Direktør Kurt Bønnelycke & Hustru Grethe Bønnelyckes Fond, Fabrikant Karl G Andersens Fond, Fausbølls Helsefond, Fonden til udvikling og uddannelse ved Nyremedicinsk Afdeling ved Aarhus Universitetshospital, Fresenius Medical Care Denmark, Frimodt-Heineke Fonden, Helen & Ejnar Bjørnows Fond, The Institute of Clinical Medicine at Aarhus University, Kirsten Anthonius’ Fond, Leo Pharmas Hypertensionslegat, Nyreforeningens Forskningsfond, Overlæge Poul M Christiansen & Hustrus Fond, Region Midtjyllands Sundhedsvidenskabelige Forskningsfond, Snedkermester Sophus Jacobsen and Hustru Astrid Jacobsens Fond. Sanofi Denmark provided original study medication (placebo and active tablets) free of charge and financially supported some meeting activity. NorDiaTech Denmark provided one Transonic Flow-QC Hemodialysis Monitor for three years including yearly calibration. The funders including Sanofi Denmark and NorDiaTech Denmark had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.