The results are in from the first long-running, randomized study to assess the relative benefits of catheter ablation vs. drug therapy to treat patients with heart failure and atrial fibrillation. The data in the eight-year trial show that ablation roundly bests drug treatment in the prevention of death, stroke and hospitalization.
The study, known as CASTLE-AF, was reported in the latest issue of The New England Journal of Medicine, along with an editorial that suggests it offers a "paradigm shift." Those results could – along with data from two other long-term studies that are due to report soon – prove sufficient to alter treatment guidelines for that population to make ablation the first-line option, rather than drugs.
Up to half of patients who present with new-onset congestive heart failure have atrial fibrillation.
"We got more than we expected," the study's lead author, Nassir Marrouche, professor in internal medicine and executive director of the Comprehensive Arrhythmia Research and Management (CARMA) Center at University of Utah Health, told BioWorld.
"We proved that we improved the LVEF [left ventricular ejection fraction] function. We proved that six-minute walk [test results] improve. We proved that the afib burden is way lower; we cut it by more than 50 percent between these two groups. It's very important that the mortality benefit gets into effect in 2.5 to three years after they were ablated, with the initial effect within three to four or six months after the initial treatment," he added.
"What we know now is that if you ablate people with low systolic ejection fraction, we can save lives, prolong lives and keep people alive in the hospital," concluded Marrouche.
The CASTLE-AF trial randomized 363 patients with heart failure, symptomatic atrial fibrillation and heart function at less than 35 percent capacity to two arms: radiofrequency catheter ablation with 179 patients or a conventional drug therapy with 184.
The patients were all either nonresponders to – or unable or unwilling to take – antiarrhythmic drugs. The drug treatment arm had treatment optimized to the current standards for rhythm and rate control. They each also had a Biotronik implanted cardioverter-defibrillator (ICD) device or a cardiac resynchronization therapy defibrillator (CRT-D) in order to include automatic daily remote monitoring capabilities. The private, Berlin-based company was also the sponsor of the study.
Ablation patients in the study had lower overall mortality at 28 percent vs. 45 percent in the medication group. They also had lower cardiovascular mortality at 13 percent, with 25 percent reported in the drug group. The rate of hospitalization for worsening heart failure was 21 percent in the ablation arm, and 26 percent in the medication arm. The risk of stroke was also cut almost in half in the ablation arm, although that result was not significant given the size of the study.
"For the first time in a randomized study, the strategy of catheter ablation for atrial fibrillation may be better than the current approach for these patients," said James Fang, chief of cardiovascular medicine at the University of Utah Health. "The CASTLE-AF clinical trial represents a landmark in the history of cardiovascular medicine because of its potential impact on our patients who are suffering from heart failure."
Added Marrouche, "This clinical trial is the first time we can show with hard data that ablation is saving more lives than arrhythmia medications. It also lowers the cost of treating patients by keeping them out of hospitals due to lower incidence of worsening heart failure."
EAST to CABANA
The study could be a first step in altering treatment guidelines that currently put drugs first. Marrouche expects that if two other long-term studies comparing ablation and drugs offer similar results, treatment guidelines will soon shift.
Those are the CABANA (Catheter Ablation vs. Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) and EAST (Early Therapy of Atrial Fibrillation for Stroke Prevention Trial) studies, which are slated to complete in June 2018 and November 2019, respectively, according to Clinicaltrials.gov.
CABANA is led by the Mayo Clinic and is designed to determine in untreated and incompletely treated afib patients if left atrial catheter ablation is superior to treatment with rate or rhythm control drugs on endpoints including total mortality, disabling stroke, serious bleeding and cardiac arrest.
EAST is being conducted by the research group Atrial Fibrillation Network. That study is designed to assess early intervention with ablation vs. antiarrhythmic drug therapy to determine which is most effective in preventing atrial fibrillation complications better than standard care.
"After all the existing studies have been published, we know a lot that ablation doesn't harm but improves function, improves quality of life and improves mortality. And now you have evidence that mortality has been improved. As you put it all together, this has to change the guidelines to recommend ablation," said Marrouche. He noted that he has already made that change for his own patients.
Ablation procedure aim to isolate pulmonary veins and restore regular heart rhythm. It is administered via a catheter into the heart to treat abnormal cells. Scarring in the heart can limit the efficacy of ablation. In this study, the ablation lesions were made at the discretion of the operators with their preferred system.
While ablation is a common option for treat drug-resistant, symptomatic atrial fibrillation in heart failure patients, the study could prove a first step in outlining it as a superior option to drug treatment. Marrouche said a large, follow-up study should aim to determine which kinds of patient benefit most from ablation.
The newly published NEJM study is unambiguous in its conclusion: "Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy."
"This is very important for millions of people who suffer from the disease, now we have a straightforward solution. Ablation has now been adopted everywhere in the world," said Marrouche, who noted that there wasn't variation in outcome due to the particular approaches to individual ablation procedures. "This can be done everywhere, and it's safe."