title: 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).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, one-year intervention trial.
  
  
  METHODS
  Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00791830.
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christian Daugaard
authors.initials: CD
authors.lastname: Peters
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Krista Dybtved
authors.initials: KD
authors.lastname: Kjaergaard
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jens Dam
authors.initials: JD
authors.lastname: Jensen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kent Lodberg
authors.initials: KL
authors.lastname: Christensen
authors.affiliation: Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Strandhave
authors.affiliation: Department of Medicine, Viborg Regional Hospital, Viborg, Denmark.
authors.forename: Ida Noerager
authors.initials: IN
authors.lastname: Tietze
authors.affiliation: Department of Medicine, Fredericia Hospital, Fredericia, Denmark.
authors.forename: Marija Kristina
authors.initials: MK
authors.lastname: Novosel
authors.affiliation: Department of Biostatistics, Aarhus University, Aarhus, Denmark.
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D000077405:Irbesartan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010919:Placebos; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D006435:Renal Dialysis; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D010919:Placebos; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000077405:Irbesartan