Withdrawal of GDMT for HF After AF Ablation not Tied to Significant Deterioration of Symptoms: JAMA
China: Researchers have found that in a pilot randomized clinical trial of carefully selected patients with atrial fibrillation who achieved normalized cardiac function and maintained sinus rhythm after catheter ablation, withdrawal of guideline-directed medical therapy (GDMT) was associated with heart failure (HF) deterioration in 13% of patients. However, the study did not find a statistically significant increase in HF worsening compared with patients who continued GDMT.
Drug-related adverse effects were more common among patients who remained on therapy. These findings suggest that, in selected patients, discontinuation of GDMT may be feasible, but larger studies are needed to determine whether GDMT can be safely withdrawn without increasing the risk of recurrent heart failure.
Published in JAMA Network Open, the DEFINITION-AF pilot randomized clinical trial by Sitong Li from the Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China, and colleagues assessed the feasibility and safety of phased withdrawal of guideline-directed medical therapy (GDMT) after successful catheter ablation in patients with atrial fibrillation (AF) and recovered cardiac function.
The open-label trial enrolled 50 adults with suspected AF-mediated cardiomyopathy who had restored sinus rhythm, normalized left ventricular ejection fraction (≥55%), normal left ventricular size, NT-proBNP levels below 250 ng/L, and no heart failure symptoms three months after ablation. Participants were randomized to either phased GDMT withdrawal or continued GDMT, with 47 completing the six-month follow-up.
The primary outcome was heart failure deterioration based on worsening cardiac function, elevated NT-proBNP, structural cardiac changes, or recurrent heart failure symptoms.
Key findings
- Heart failure deterioration occurred in 3 of 23 patients (13%) in the GDMT withdrawal group, while no patients in the continuation group experienced deterioration; however, the difference was not statistically significant.
- Reintroduction of GDMT in all three patients with heart failure deterioration resulted in recovery of left ventricular function or normalization of NT-proBNP levels.
- No cardiovascular events occurred in either treatment group during the six-month follow-up.
- Changes in left ventricular function, cardiac magnetic resonance findings, quality-of-life scores, and atrial arrhythmia recurrence were similar between the withdrawal and continuation groups.
- NT-proBNP levels decreased more in patients who continued GDMT than in those who discontinued therapy.
- Drug-related adverse events were reported only in the continuation group (20.8%) and were absent among patients who underwent GDMT withdrawal.
The researchers noted that the pilot design, small sample size, and six-month follow-up limit the strength of the findings. They also acknowledged that some patients in the withdrawal group remained on certain GDMT components, and genetic testing and detailed assessment of irreversible atrial remodeling were not performed.
Overall, the findings suggest that phased GDMT withdrawal may be feasible in carefully selected patients with AF who recover cardiac function after catheter ablation. However, the authors stress that larger, long-term randomized trials are needed before routine discontinuation of heart failure medications can be recommended.
Reference:
Li S, Sun Y, Lai Y, et al. Heart Failure Medication Withdrawal in Patients With Improved Cardiac Function After Atrial Fibrillation Ablation: The DEFINITION-AF Pilot Randomized Clinical Trial. JAMA Netw Open. 2026;9(6):e2620145. doi:10.1001/jamanetworkopen.2026.20145
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