SAN DIEGO, CA—Patients undergoing left atrial appendage closure (LAAC) for stroke prevention appear to fare equally well postprocedure with just a single antithrombotic agent, according to a new study presented this week at TCT 2026.
Two different strategies—monotherapy with aspirin or a reduced-dose non-vitamin K oral anticoagulant (NOAC)—were both noninferior to dual antiplatelet therapy (DAPT) for the primary composite endpoint of death, stroke, systemic embolism, or major bleeding at 6 months post-LAAC.
“Overall, we can say that monotherapy is probably the way to go, simplified for most patients,” senior investigator Saibal Kar, MD (Los Robles Hospital and Medical Center, Thousand Oaks, CA), said during a media briefing. “Now, I have to caveat this: this study included patients who had an uncomplicated and complete closure at the time of procedure. This doesn’t take into consideration patients who had a complication.”
SIMPLAAFY was not designed to directly compare aspirin to reduced-dose NOAC therapy, although those treated with aspirin had the lowest overall rate of the study’s primary endpoint. Device-related thrombus (DRT) assessed at 45 days was lowest in those treated with the reduced-dose NOAC.
“Even though we didn’t do a prespecified analysis comparing the two monotherapy arms, it appeared in the study that aspirin had the lowest bleeding risk, and this is not surprising,” Kar told Cardiology Now News. “However, there was also a slightly increased rate of DRT at 45 days. So, we have to balance both, and that’s why we didn’t want to come out and stay that a single antiplatelet is the right way to go for all patients.”
In patients referred for LAAC because of a high risk for bleeding, Kar said he’d likely recommend low-dose aspirin as the postimplant antithrombotic regimen. On the other hand, if a patient arrived with a “history of stroke, ‘smoke’ in the left atrium, and an [ejection fraction] around 40%, I would go for low-dose NOACs for 3 months followed by baby aspirin.”
Pinak Shah, MD (Brigham and Women’s Hospital, Boston, MA), who spoke during the morning press conference, called SIMPLAAFY an important trial for the field.
“I think we now have very good data showing that monotherapy is appropriate,” he said. “I don’t know if I would say that aspirin is going to be the first way to go for most of these patients. I think if they are low bleeding risk, then it makes sense, but the higher risk of DRT is something to think about.”
Antithrombotic Therapy After Watchman
There is no consensus on the correct choice of antithrombotic therapy immediately following LAAC. While LAAC-eligible patients are typically at higher risk for bleeding, postimplant antithrombotic therapy is needed for device endothelialization and healing. In the past, different antithrombotic options have included a NOAC plus aspirin followed by DAPT, oral anticoagulation/NOAC alone, or DAPT alone, say investigators.
“The randomized evidence of simplified antithrombotic strategies are quite limited,” said Kar.
In SIMPLAAFY, researchers randomized patients within 24 hours of a successful and uncomplicated LAAC (Watchman FLX Pro; Boston Scientific) to one of three treatment arms: 1) aspirin 81 to 100 mg/day (n = 613) for the entire 12-month study period; 2) reduced-dose NOAC, (n =620) for 3 months followed by aspirin; and 3) DAPT with clopidogrel 75 mg/day and aspirin (n = 624) for 6 months followed by aspirin alone.
The majority of patients (83.9%) in the reduced-dose NOAC arm were treated with apixaban 2.5 mg twice daily and 13.5% received rivaroxaban 10 mg daily. Baseline characteristics were well- balanced across the three groups. Most patients (62.2%) were 75 years or older and 42.9% were female. The mean CHA2DS2-VASc score was 4.2; the mean HAS-BLED bleeding score was 2.6.
It appeared in the study that aspirin had the lowest bleeding risk, and this is not surprising.
Saibal Kar
At 6 months, the primary composite endpoint of death, stroke, systemic embolism, or major bleeding occurred in 3.3% of the aspirin-treated patients versus 6.9% of those treated with DAPT. The absolute rate difference between treatments fell below the prespecified noninferiority margin of 7.2% (P < 0.001).
In the reduced-dose NOAC group, the primary composite endpoint occurred in 5.1%. Compared with the rate of 6.9% in the DAPT group, the absolute rate difference also fell within the prespecified noninferiority margin of 7.2% (P < 0.001).
There was no significant difference in stroke risk, including ischemic and hemorrhagic events, with aspirin or reduced-dose NOAC compared with DAPT.
In exploratory analyses, the rate of major or clinically relevant nonmajor bleeding was 12.8% in those treated with DAPT, 7.3% in those treated with reduced-dose NOAC, and 5.5% in those randomized to aspirin. Both comparisons to DAPT were statistically significant. Major bleeding was significantly lower with aspirin, but not with reduced-dose NOAC, compared with DAPT.
At 45 days, DRT was seen in 3.4% of patients treated with DAPT, in 2.7% of those who received aspirin alone, and 0.9% of those treated with a reduced-dose NOAC.
Follow-up will continue until 12 months.
No Consensus on Optimal Treatment
Mohamad Alkhouli, MD (Mayo Clinic, Rochester, MN), said “there are few things” more confusing in structural heart interventions than antithrombotic therapy after LAAC. “If you survey physicians globally, you’ll find heterogenous practices, mostly emerging from the lack of any legitimate evidence to guide our approaches,” he said following the late-breaking trial presentation.
While SIMPLAAFY has limitations, including a substantially lower than anticipated event rate in the DAPT arm, Alkhouli said that if focusing only on outcomes in the three study arms, “aspirin seems to emerge as the winner.” He acknowledged, however, that the jury remains out.
Bernard Prendergast, MD (St. Thomas’ Hospital and Cleveland Clinic London, UK), a member of the panel, expressed concern about the risks of thrombus after LAAC, and questioned why operators don’t opt for reduced-dose NOAC as the default option given the low risk of bleeding and better DRT outcomes.
Kar, for his part, pointed to the ANDES trial, a study presented earlier in the TCT meeting and published as a research letter in JACC. In that study, patients were treated with a direct oral anticoagulant or DAPT for 60 days and then switched to single antiplatelet therapy. There was no difference in the risk of death, ischemic stroke, or systemic embolism at 1 year in the treatment arms, but bleeding, specifically minor bleeding, was lower in the DOAC-treated patients. DRT rates were numerically higher with oral anticoagulation.
“That’s the reason I keep things open,” said Kar. “Now, having said that, [SIMPLAAFY] did show that low-dose NOACs are not innocent. The bleeding was higher in the low-dose NOAC group compared with baby aspirin.”
When it comes to antithrombotic therapy post-LAAC, Alkhouli said a personalized approach is likely best over standardized recommendations. He also thinks more basic research is needed to better understand endothelialization and risks of DRT. The Watchman FLX Pro used in this study is the latest, best-in-class device and yet DRT remains an issue, he said.
“It’s a coated device, it’s been shown to be safe, and yet we still haven’t been able to get rid of DRT,” he said. “Is this something that will stick with us for life and how are we going to approach it?”
Source:
Reddy VY, Saliba WI, Waggoner T, et al. Antithrombotic therapy after left atrial appendage occlusion: the SIMPLAAFY randomized clinical trial. JAMA. Published online November 2, 2026.
Disclosures:
Kar reports research support and consulting fees from Abbott and research support from Boston Scientific.
Alkhouli reports consulting fees/honoraria/grant from Boston Scientific and Abbott and grant/research support from Boston Scientific.
Prendergast reports consulting fees/honoraria from Edwards Lifesciences.