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

Background and AimLittle 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.DesignRandomized, double-blind, placebo-controlled, one-year intervention trial.Setting and ParticipantsEighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year.InterventionIrbesartan/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 MeasurementsCardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension.ResultsAt 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.ConclusionUse 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 registrationClinicaltrials.gov NCT00791830

One-year Serial Measurements of High-sensitivity Troponin T in Hemodialysis Patients A Randomized Placebo-controlled Sub-study Investigating Angiotensin-II-Blockade, Variation Over Time and Associations with Clinical Outcome

“…The study protocol and results on intermediate CV endpoints and residual renal function have previously been published (19)(20)(21)(22). Briefly, the SAFIR-study (acronym for "SAving residual renal Function in hemodialysis patients receiving IRbesartan) was designed as a double blind multicenter randomized placebo-controlled trial primarily focusing on residual renal function and intermediate CV endpoints.…”

“…All dialysis sessions in the study period were reviewed for episodes of intradialytic hypotension (IDH) defined as symptomatic hypotension requiring administration of intravenous fluid or preterm ending of the dialysis session as described previously (22). Cardiac output (CO) was measured in duplicate by injecting a bolus of 30 mL 37 °C isotonic saline into the venous blood line within the first and the last 30 minutes of the dialysis session using a previously validated method (Hemodialysis Monitor HD02/HD03, Flow-QC tubing sets, and clip on flow/dilution sensors Transonic Systems Inc., Ithaca, NY, USA) as previously described (22). The mean arterial blood pressure (MAP), total peripheral resistance (TPR), and stroke volume (SV) were derived by:…”

“…Improvement of cardiac performance via LV-regression due to blockade of the reninangiotensin-aldosterone system (RAAS) should thus potentially lower TnT-levels. The aim of the present study was therefore to investigate the effect of the ARB irbesartan on TnT-levels, short and long-term variation in TnT and associations with various clinical and dialysis related parameters in a cohort of newly started HD patients participating in the SAFIR study (19)(20)(21)(22).…”

High-sensitivity Troponin T in hemodialysis patients: a randomized placebo-controlled sub-study investigating angiotensin-II-blockade, variation over time and associations with clinical outcome

“…Primary results regarding residual renal function and intermediate CV endpoints have been published previously together with the study protocol [ 19 – 22 ]. Briefly, the SAFIR-study (acronym for” SAving residual renal Function in hemodialysis patients receiving IRbesartan) was designed as a randomized double-blind placebo-controlled multicenter trial.…”

“…Improvement of cardiac performance via LV-regression due to blockade of the renin-angiotensin-aldosterone system (RAAS) should thus potentially lower TnT-levels. The aim of the present study was therefore to investigate the effect of the ARB irbesartan on TnT-levels, short and long-term variation in TnT and associations with various clinical and dialysis related parameters in a cohort of newly started HD patients participating in the SAFIR study [ 19 – 22 ].…”