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
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
“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-McLaughlin Heart and 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.