RAFT: CRT, ICD plus medical therapy beneficial in patients with mild-to-moderate HF
American Heart Association Scientific Sessions 2010
CHICAGO — Rates of mortality and hospitalization were lower in patients with mild-to-moderate HF who were treated with cardiac resynchronization therapy, implantable cardioverter defibrillators and medical therapy compared with those treated with implantable cardioverter defibrillators and medical therapy alone, new study data suggested.
The RAFT was a parallel, randomized control trial featuring patients with NYHA class II or III HF, left ventricular ejection fraction ¡Ü30% and wide QRS duration. In addition to medical therapy, patients received either an ICD (n=904) or an ICD with cardiac resynchronization therapy (CRT; n=894).
After a mean follow-up of 40 months, the primary outcome of composite of all-cause mortality or hospitalization for HF was observed in 33.2% of patients in the ICD-CRT arm and 40.3% of those in the ICD arm (ICD-CRT HR=0.75; 95% CI, 0.64-0.87). The secondary outcomes all favored the ICD-CRT group, including rates of death from any cause (6.1% vs. 20.8%; P=.003), death from CV cause (17.9% vs. 14.5%; P=.019) and rates of hospitalization for HF (26.1% vs. 19.5; P¡Ü.0001).
Among patients in this study, Anthony S.L. Tang, MD, with the Royal Jubilee Hospital, Victoria, British Columbia, Canada, and trial researcher concluded in a news conference, ¡°The addition of CRT to ICD reduces death and hospitalization for HF, and reduces all-cause mortality with an absolute reduction of 6% over a treatment period of 5 years. This translates to 14 patients needing to be treated for 5 years to prevent one death. We also demonstrated that [CRT plus ICD] reduces hospitalization for HF, translating to 11 patients needing to be treated for 5 years to prevent one hospitalization for HF.¡±
Dr. Tang has received research support MedTronic, St. Jude Medical and Boston Scientific. - by Brian Ellis
For more information:
Tang ASL. LBCT I, Abstract 21768 . Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
The first statement that can be made is that there is no longer any need for equipoise. It is very clearly evident that the ICD-CRT combination works and works well in patients with mild-to-moderate HF.
The next thing that represents a take home [message] is that we will have to revisit our clinical practice guidelines and understand that we will need to expand the indications from those with class III or ambulatoryclass IV HF to those that have lesser degrees of HF with regards to severity. Importantly, we should then anticipate that to a certain extent clinical practice should change. But we also need to be somewhat circumspect. We¡¯re waiting for the cost-effectiveness data from this investigation. We have to understand there is a finite risk of certain morbid events that are important to patients, and we increasingly struggle with how be best characterize the phenotype of patient that responds to CRT.
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ASCEND-HF: Nesiritide did not improve outcomes in decompensated HF
American Heart Association Scientific Sessions 2010
CHICAGO – Nesiritide was not associated with a statistically significant reduction in dyspnea, rehospitalization or death among patients with acute decompensated HF, according to late-breaking data from the ASCEND-HF trial.
Researchers enrolled 7,141 patients with severe HF to determine whether nesiritide (Natrecor, Scios) was superior to placebo in reducing the HF-related hospitalization rate or all-cause mortality at 30 days and improvement in dyspnea at six or 24 hours. Safety endpoints included all-cause mortality, renal function and both symptomatic and asymptomatic hypotension.
Patients were randomly assigned to continuous intravenous nesiritide or placebo plus standard treatment for 30 days.
Compared with placebo, nesiritide was not associated with a reduction in 30-day death or HF rehospitalization (10.1% vs. 9.4%; P=.31). Nesiritide improved dyspnea at 6 hours (15.0% vs. 13.4%; P=.030) and at 24 hours compared vs. placebo (30.4% vs. 27.5%; P=.007), but the differences did not meet the study’s protocol criteria for statistical significance.
“No evidence of a major benefit lead us to a situation as an executive committee to say that, in terms of clinical implications, we need to show people the data and they can make their decisions about the value of the effect of this drug on dyspnea,” Robert M. Califf, MD, researcher and vice chancellor for clinical research at Duke University School of Medicine in Durham, said during a press conference. “It certainly does not have a long-term effect on clinical outcomes one way or the other.”
Data from previous meta-analyses linked nesiritide with reduced renal function. However, data from ASCEND-HF showed no association between the two. According to Califf, there was an expected increase in hypotension among patients in the treatment arm vs. placebo (26.6% vs. 15.3%; P<.001).
“[W]hat I think is most important about this trial [is that] we constantly put drugs on the market without doing the right outcome trials,” Califf said. “If this outcome trial had been done earlier, clinicians and patients would’ve had a much better idea of the potential, very limited role of this treatment but they also would’ve known that it was not harmful.”
Dr. Braunwald reports receiving research support from Johnson and Johnson and is a member of the Cardiorentis Scientific Advisory Board. - by Stacey L. Fisher
For more information:
Califf R. LBCT I, Abstract 21828. Presented at: American Heart Association Scientific Sessions 2010; Nov. 13-17; Chicago.
The good news for nesiritide from the ASCEND-HF trial [is that] it does not support the concerns raised by Sackner-Bernstein and colleagues in their two meta-analyses. [There is] no evidence of nesiritide being associated with an increased risk for mortality and renal dysfunction. This really joins the FUSION II trial conducted by Yancy and colleagues. The less good news for nesiritide is that the trial provides very little evidence that its addition would improve the outcome of patients with acute decompensated HF who are receiving excellent standard care. The economic implications for widespread use of a drug with these effects are self evident. ASCEND-HF joins a large number of other trials conducted with a variety of agents since the 1970s in acute HF who have not shown clinical benefit. How to improve outcomes in this very common condition remains a serious challenge.