CRT-D Offers Persistent Survival Benefit in Long-term RAFT Results

The survival benefit of a cardiac resynchronization therapy-defibrillator (CRT-D) lasts for several years in patients with mild-to-moderate symptoms of heart failure (HF), a reduced ejection fraction, and a wide QRS complex, according to extended follow-up of the RAFT trial.

Back when the main trial results were published back in 2010, investigators reported a 5.3% lower absolute rate of all-cause death among patients treated with a CRT-D versus an implantable cardioverter-defibrillator (ICD) alone, at a mean follow-up of 3.3 years.

Now, in an analysis that extends follow-up out to a median of 7.7 years overall and 13.9 years among survivors, the advantage for CRT-D in the rate of all-cause death remained roughly the same at 5.2%, John Sapp, MD (Dalhousie University, Halifax, Canada), and colleagues report in the January 18, 2024, issue of the New England Journal of Medicine.

That was a bit of a surprise, Sapp told TCTMD, because patients would have started crossing over to other treatments at the end of the trial, which would be expected to bring the survival curves together over time.

Having these long-term data on the magnitude of the expected benefit of CRT-D implantation will be useful when discussing treatment options with patients, Sapp indicated. “If you have to weigh that against risks of a procedure, for example, getting a really good understanding of the potential benefits is important.”

RAFT Long-Term Study

Across multiple trials, CRT has been shown to reduce mortality and HF outcomes among patients with symptomatic HF, a reduced LVEF, and a wide QRS interval, and it has since become standard in appropriately selected patients.

One of those trials was RAFT, which completed enrollment in February 2009. The main results showed that receipt of a CRT-D versus an ICD—both on top of optimal medical therapy—reduced the risk of death or hospitalization for HF (HR 0.75; 95% CI 0.64-0.87), as well as all-cause and CV death and hospitalization for HF alone.

Of the 1,798 patients in the trial, the RAFT Long-Term Study followed the 1,050 participants (mean age 66.5; 83.8% men) who were included at the eight highest-enrolling sites.

Through the extended follow-up, patients who received an CRT-D remained less likely to die from any cause (71.2% vs 76.4%; 0.80; 95% CI 0.69-0.92). They also had a slightly lower risk of a composite of all-cause death, heart transplantation, or implantation of a ventricular assist device (75.4% vs 77.7%; 0.85; 95% CI 0.74-0.98).

I think this really helps shift us into thinking about longer-term survival for people who still have relatively good functional capacity, and we want to invest in helping them stay alive for a long time. Lynne Warner Stevenson

“CRT has been shown to result in significant improvement in cardiac performance and to lead to reverse remodeling, a reduction in new-onset ventricular arrhythmias, and improved clinical outcomes,” Sapp et al write. “It is possible that these beneficial early effects may be associated with the much longer-term improvements in overall survival shown in our trial.”

They note, too, that the better outcomes in the CRT-D group were seen even though certain groups of patients who do not respond as well to the treatment—such as those with atrial fibrillation or without left bundle branch block (LBBB)—were included.

“Furthermore,” the investigators write, “the survival benefit remained despite the fact that the long-term nature of this trial limited the analysis of subtle variations in clinical occurrences during the trial period, such as worsening of heart failure, changes to pharmacologic management, crossover between the treatment groups, or a change in the function of implanted leads—all examples of nonfatal, yet important changes that may reduce the effectiveness of CRT.”

Eyeing Earlier Treatment With CRT

Speaking with TCTMD, Lynne Warner Stevenson, MD, who wrote an accompanying editorial with Jay Montgomery, MD (both from Vanderbilt University, Nashville, TN), said it’s important to have these longer-term data because the full impact of various treatments in patients who do not yet have advanced disease may not become apparent for many years.

She drew a parallel between these long-term RAFT results and those from a landmark analysis of the SOLVD trial of enalapril, which showed that treatment improved survival among asymptomatic patients with LV systolic dysfunction through 12 years of follow-up.

“I think this really helps shift us into thinking about longer-term survival for people who still have relatively good functional capacity, and we want to invest in helping them stay alive for a long time,” Stevenson said.

The idea is that “starting early has a benefit that you can’t necessarily catch up for if you wait until later in the disease,” she said. “The early starting of a therapy in order to get the longest benefit is a lot of the message that I got from this and the message that we tried to convey in the editorial—that we really want more good quality time, so we need to start early.”

A remaining question is whether CRT will continue to have the same impact in the setting of improved medical therapies for HF, which now include neprilysin inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Stevenson said it’s hard to predict how these agents my change disease trajectory, but pointed out that patients with LBBB (the usual indication for CRT) have been shown to have less improvement in LVEF with guideline-directed medical therapy than patients with other QRS morphologies.

Sapp also said the answer to that question is unknown, but added, “I would be surprised if [CRT] didn’t have an additive independent benefit” because it works via a different mechanism than the guideline-directed medical therapies for HF.

Regardless of how these drugs impact patients down the road, Stevenson underscored the call to consider earlier treatment with CRT to improve patient outcomes.

“This really makes me want to try to treat that left bundle branch block sooner in these patients even if they’re still pretty well compensated with their heart failure,” she said, adding that physicians should be aiming to treat the underlying disease rather than the associated symptoms.

“I think we should be looking at when the ejection fraction has started to fall in terms of CRT in those patients who have a left bundle branch block and think about doing CRT right away and not waiting until there’s evidence of more symptomatic heart failure.”