Antithrombotic therapy in AFib care post procedures
Investigators in four trials presented findings in Saturday’s Late-Breaking Science session, “Dilemmas in Antithrombotic Therapy in AFib Care Post Procedures.” They found:
- NOAC monotherapy beats combination therapy for AFib patients after DES implantation.
- One month of dual antithrombotic therapy is noninferior to 12 months for patients with AFib after PCI.
- Medical care beats left atrial appendage closure for older patients at high risk for stroke, bleeding.
- There is no stroke benefit from continuing anticoagulation beyond 12 months after catheter ablation for AFib.
Monotherapy with a single nonvitamin K antagonist oral anticoagulant (NOAC) is superior to NOAC + clopidogrel combination therapy for atrial fibrillation (AFib) patients who are clinically stable one year after drug-eluting stent (DES) implantation. NOAC monotherapy reduced the risk of net adverse clinical events by 46% and the risk of major or clinically relevant bleeding by 62% compared with combination therapy with no significant difference in ischemic events.
Jung-Sun Kim, MD, PhD
ADAPT AF-DES enrolled 960 patients with AFib, who had been clinically stable following DES implantation for at least 12 months across 32 centers in South Korea. Patients were randomized to NOAC monotherapy (482) or NOAC + clopidogrel (478). Patients had a mean age of 71.1 years, and 21.4% were women.
The primary outcome was net adverse clinical events, a composite of all-cause mortality, myocardial infarction, stent thrombosis, stroke, systemic embolism or major/clinically relevant nonmajor bleeding. The trial was designed as a noninferiority study, with superiority testing planned if noninferiority was shown.
After 12 months of follow-up, the primary endpoint had occurred in 9.6% of the NOAC monotherapy arm vs. 17.2% in the combination arm, a mean difference of -7.6% for a hazard ratio of 0.54 (95% CI: 0.37 to 0.77, p<0.001). Major or clinically relevant nonmajor bleeding occurred in 5.3% and 13.3% of the monotherapy and combination arms respectively for HR 0.38 (95% CI: 0.24 to 0.60).
The incidence of major adverse cardiovascular events, a combination of cardiovascular death, myocardial infarction, stent thrombosis, ischemic stroke, or systemic embolism, was similar between the arms, HR 0.84 (95% CI: 0.43 to 1.63).
“In the patient with AFib who is stable beyond one year of drug-eluting stent implantation, NOAC monotherapy provides a simpler and safer long-term strategy than combination therapy,” Kim said. “The superiority of monotherapy is driven by significant reductions in bleeding without increasing ischemic events. In real-world practice, we can deescalate to monotherapy and thereby minimize bleeding while maintaining protection against thrombotic events.”
Patients in ADAPT AF-DES are being followed for an additional two years, Kim said. Longer term data will be reported at a later date.
30 days antithrombotic therapy not inferior to one year after PCI for patients with AFib
What may be the first trial of short-term antithrombotic therapy for patients with AFib following percutaneous coronary intervention (PCI) found that one month of dual therapy is not inferior to 12 months of therapy for mortality or thrombotic events. The shorter intervention was superior for bleeding outcomes.
Yohei Sotomi, MD, PhD
The OPTIMA-AF trial randomized 1,088 patients with AFib undergoing PCI. Patients received either one month of dual therapy with a direct oral anticoagulant (DOAC) plus a P2Y12 inhibitor followed by DOAC monotherapy (542 patients) or to 12 months of dual therapy (537 patients). The open label trial was conducted across 75 sites in Japan between October 2019 and September 2024.
The primary efficacy endpoint was a composite of all-cause mortality or thromboembolic events, including myocardial infarction, stroke or systemic embolism, at 12 months.
The primary safety endpoint was major or clinically relevant nonmajor bleeding at 12 months.
The primary efficacy endpoint occurred in 5.4% of the 1-month arm vs. 4.5% of the 12-month arm for an absolute difference of 0.9%, p=0.002 for noninferiority and p=0.597 for superiority.
The primary safety endpoint occurred in 4.8% of the 1-month arm vs. 9.5% of the 12-month arm (p=0.004 for superiority).
“These results may help doctors feel more confident in using shorter duration of dual antithrombotic therapy in selected patients with AFib after PCI, Sotomi said. “One of the limitations of our study is that it mainly included patients with stable coronary syndrome, stable angina or silent myocardial ischemia. Our next step is to evaluate short duration antithrombotic therapy in acute coronary syndrome.”
Medical care better than device closure for AFib patients at increased risk of stroke, bleeding
The largest clinical trial to date comparing catheter-based left atrial appendage closure (LAA) to physician-directed medical care for patients with atrial fibrillation (AFib) support current guidelines recommending medical care for patients at high risk of stroke and major bleeding. LAA was not noninferior to physician-directed medical care for a combined primary endpoint of stroke, systemic embolism, cardiovascular/unexplained death or major bleeding in a group of older, high-risk patients.
Ulf Landmesser, MD
Current guidelines in the U.S. and Europe recommend oral anticoagulation for patients with AFib at high risk of stroke and major bleeding. But the recommendations are weak, Landmesser noted, clearly indicating the need for more evidence.
The CLOSURE-AF trial was designed to compare LAA to physician-directed best usual medical care, including direct oral anticoagulation (DOAC) for eligible patients, in older adults with AFib who are at high risk for both stroke and bleeding. The trial was conducted across 46 sites in Germany.
A total of 446 patients were randomized to LAA and 442 to physician-recommended medical care. Patients had a mean age of 79.1 years, 38.6% were female, and most, 93.6%, were Caucasian because study sites were all in Germany. The mean CHA2DS2-VASc Score was 2, and the mean HAS-BLED score was 3.0.
The primary endpoint was a composite of stroke, systemic embolism, cardiovascular or unexplained death, or major bleeding over three years. Secondary endpoints included individual components of the primary endpoint and all-cause mortality over three years.
LAA closure did not outperform medical care as expected, with
an adjusted hazard ratio of 1.28 (95% CI; 1.01 to 1.62) for the combined primary endpoint on an intent-to-treat analysis and HR 1.34 (95% CI: 1.04 to 1.72) based on per protocol analysis.
There were no statistically significant differences in any of the secondary endpoints between the groups.
Dr. Landmesser concluded that the findings suggest standard physician-directed medical care, including blood thinners for eligible patients, remains a valid management option for those older patients with irregular heartbeat who are at very high risk for stroke and bleeding.
No benefit to continued oral coagulation for stroke in moderate risk patients after successful catheter ablation for AFib
A major trial of oral anticoagulation to reduce stroke following successful catheter ablation for AFib was halted early for futility. The rate of stroke was so low the data safety monitoring board judged it would be impossible to show a difference in stroke risk between ongoing anticoagulation and discontinuation.
Atul Verma, MD
There has been little solid evidence on the rates of stroke and recurrent AFib following catheter ablation for AFib, Verma said, so guidelines take a cautious approach. Patients with known risk factors for stroke are routinely advised to continue oral anticoagulation beyond the first year following catheter ablation. OCEAN was designed to assess the need for oral anticoagulation in the presence of risk factors for stroke one year after successful catheter ablation.
Patients who were at least 12 months after successful catheter ablation for AFib were randomized to either rivaroxaban or aspirin. All patients had at least one Holter monitor assessment showing normal sinus rhythm during both the first and second six months after ablation and a third 48-hour assessment before enrollment. All had a CHA2DS2-VASc score of at least one for males and at least two for females. There was no upper limit to CHA2DS2-VASc score.
OCEAN had a planned enrollment of 1,572, Varma said, but enrollment was stopped at 1,283, 641 in the rivaroxaban arm and 642 in the aspirin arm. The relative risk for rivaroxaban was 0.72 (95% CI: 0.23 to 2.25). There was a numerical increase in major bleeding in the rivaroxaban arm and a statistically significant increase in minor or clinically relevant bleeding compared to the aspirin arm.
“We were unable to detect any benefit of rivaroxaban over aspirin in this patient population,” Varma said. “Our mean CHA2DS2-VASc score was 2.2, and we had about 30% of patients with a CHA2DS2-VASc score of three or more, and 10% with a score of four or more. For moderate risk patients with a CHA2DS2-VASc score of one to four, our results are applicable. But our results should probably not be applied to very high-risk patients.”
