Findings from the AFFIRM trial found increased risks after stopping oral anticoagulant therapy after rhythm control, and the same is true for stopping treatment with oral anticoagulants after successful ablation.
Although much of the literature advocates for either stopping treatment with oral anticoagulants (OACs) after successful ablation or continuing long-term OAC therapy, experts in a session at the American College of Cardiology 2023 Scientific Session suggested that there may be a middle road.
In his presentation, panelist Rod S. Passman, MD, director of the Center for Arrhythmia Research at the Northwestern Feinberg School of Medicine, said monitoring heart rhythm and taking a “pill-in-pocket” approach could both minimize costs and avoid the negative effects of lifelong OAC therapy.
Findings from the AFFIRM trial found increased risks after stopping OAC therapy after rhythm control, and the same is true for stopping treatment with OACs after successful ablation. One study Passman cited found a 2.5-fold increased risk of stroke. Continuing therapy with OACs also has significant risks, with between a 2.1% and 3.6% increased risk of major bleeds each year, and an increased risk of minor bleeds up to 18% per year.
“While they’d be minor bleeds to you, this is a common reason why people stop taking oral anticoagulation,” Passman said, noting that approximately half of patients in one study had stopped OAC therapy within 2 years of starting.
Instead, a pill-in-pocket approach would give patients OACs only as needed for a few weeks and only in response to a prolonged episode of atrial fibrillation (AF). To convince clinicians to do this, however, Passman noted that he would need to prove several factors, including whether AF is the cause or a marker for stroke.
The atrial myopathy model believes that patients have a source of stroke from non-atrial mechanisms as well as an abnormal atrial substrate, leading to stroke even when eliminating AF. Some studies, including the TRENDS, ASSERT, and IMPACT trials, have shown that many strokes occur temporarily disassociated from the AF; however, Passman noted several issues with these findings.
“All of these patients had multiple other risk factors for stroke…[and] no effort was made to adjudicate the mechanism of the stroke,” Passman said. “So how do we know these are cardioembolic events?”
Instead of the atrial myopathy model, Passman argued for a case-crossover approach. In one study that he was involved in, Passman said researchers combined 2 large databases and found approximately 891 patients with a clearly documented stroke.
The study found that the odds of having a prolonged episode of AF in the months prior to the stroke was nearly 4-fold, and the association between stroke and AF was strong. Notably, the risk of stroke increases by 5-fold in the first week after a prolonged AF episode, according to the study findings.
Based on these findings, Passman argued that there is a clear causal relationship between AF and stroke risk. With that established, 2 pilot studies—REACT.COM and TACTIC-AF—have investigated the pill-in-pocket approach.
Together, the 2 studies enrolled 96 patients and had 112 patient-years of follow-up. According to the results, the approach led to a 94% and 75% respective reduction in time on OACs and no strokes occurred in the patient population. These findings suggest that the pill-in-pocket approach is feasible, according to Passman, who added that the next obstacle will be proving that it is safe.
“Can we leverage these advances in both pharmacology and technology to envision a pill-in-pocket approach using a wearable device?” he asked.
To that end, the REACT-AF study is about to be launched to investigate this further. Passman concluded that the pill-in-pocket approach reduces time on anticoagulation, as well as reduces bleeding events and costs, and improves patients’ quality of life. If adopted, the approach would also change indications for rhythm control, limiting patients’ exposure to lifelong anticoagulation.
Presenter Atul Verma, MD, head of the Heart Rhythm Program at Southlake Regional Health Center, discussed similar issues as well as an upcoming trial comparing OAC strategies. Verma noted that guidelines currently say that decisions regarding continuing systemic OACs more than 2 months after ablation should be based on stroke risk profile and whether the ablation was successful, but, importantly, the evidence for this recommendation is grade C.
Patients frequently wish to discontinue treatment with OACs after ablation, but late recurrence of AF does continue. Even if the procedure seems successful at 1 year, there is a slight decline year-over-year in the paroxysmal AF population, and a more significant decline in the non-paroxysmal AF population. Researchers have also found that prior to ablation, most episodes of AF were symptomatic, whereas they tend to be more asymptomatic after ablation.
“Just because we think we have cured the patient doesn’t necessarily mean that they’re not having further AF,” Verma said.
Although there are studies investigating OAC use post-ablation, Verma said most of these data are older and not good quality, necessitating new, better research. To that aim, the OCEAN trial will be comparing a strategy of OAC to aspirin alone for reducing the risk of stroke, systemic embolism, or silent cerebral infarction post-successful ablation of AF in patients with a CHADS (Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke history) score of 1 or more.
The primary outcome of the trial is a composite of stroke, systemic embolism, and covert embolic stroke, which is defined as large cerebral lesions >15 mm. Verma said covert embolic stroke was specifically chosen because it tends to occur between 2 and 7 times more frequently than clinical stroke and is increasingly used as a surrogate in trials.
The trial has an estimated sample size of 1572 patients and includes patients considered “successful” at least 1 year after ablation, regardless of the number of previous ablation procedures they have received. Patients were randomized to either aspirin or rivaroxaban and followed for up for 36 months, with a repeated cerebral MRI at 12 and 36 months. A subset of patients was also implanted with a loop recorder (ILR) to look for asymptomatic AF.
The Data and Safety Monitoring Board recommended early trial termination at 1284 patients enrolled, approximately 200 of whom received an ILR. The participants will be followed for 36 months and Verma said there are still approximately 18 months to go, but he looks forward to presenting the results in the future.
Verma A, Passman RS. Oral Anticoagulants Before and After AF Rhythm Control Strategies. Presented at American College of Cardiology 2023 Scientific Session. March 4, 2023.