Cardiology Today | November 18 2010
All-cause and CV mortality, as well as HF-associated hospital stays, were significantly lower in patients with hemodialysis and chronic HF who were treated with telmisartan, new data suggested.
“To the best of our knowledge, our results are the first to provide evidence that the addition of an [angiotensin II type 1 receptor blocker], namely telmisartan, to regimens, including various combination of ACE inhibitor, digitalis, and beta-blockers, is feasible and beneficial in end-stage renal disease patients with chronic HF receiving dialysis treatment,” the researchers wrote.
The 3-year, randomized, double blind, placebo-controlled, multicenter trial was performed in 30 Italian clinics featuring hemodialysis patients with chronic HF (NYHA Class II to III; left ventricular ejection fraction ≤40%). Besides ACE inhibitor therapy, patients were randomly assigned telmisartan (Micardis, Boehringer Ingelheim; n=165; target dose, 80 mg) or placebo (n=167).
During a mean follow-up of 35.5 ± 8.5 months, researchers reported a significant reduction for all three primary endpoints in patients taking telmisartan vs. placebo: all-cause mortality (35.1% vs. 54.4%; P<.001), CV death (30.3% vs. 43.7%; P<.001) and hospital admission for chronic HF (33.9% vs. 55.1%; P<.0001).
Additionally, Cox proportional hazards analysis revealed telmisartan to be an independent determinant of all-cause mortality (HR=0.51; 95% CI, 0.32-0.82), CV mortality (HR=0.42; 95% CI, 0.38-0.61) and hospital stay for chronic HF decompensation (HR=0.38; 95% CI, 0.19-0.51).
Such beneficial effects of telmisartan as seen in the trial, the researchers noted, “were evident within 6 months from the beginning of the treatment and persisted for the entire treatment period. … Although further larger trials in hemodialyzed patients with [chronic] HF are desirable, our experience could offer clinicians an opportunity to make additional improvements in the poor prognosis of end-stage renal disease patients with chronic HF.”
“Although the power calculations in the present study showed 90% power, this was to detect a 50% hazard reduction in death, not a commonly seen magnitude of benefit with most agents in any clinical trial setting,” Ilke Sipahi, MD, and James C. Fang, MD, of the Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, wrote in an accompanying editorial. “Given this aggressive target of event-reduction benefit and a modest total number of patients (which is comparable to a ‘pilot’ trial), it is not clear whether this trial provides enough power to be definitive.”
Despite this, the findings are important and should lead to further investigation. However, “For now, clinicians should carefully evaluate the choice of agents in the treatment of HF when it complicates dialysis and make sure that drugs that antagonize both the [renin-angiotensin system] and adrenergic axes are considered,” Sipahi and Fang said.