Signs Point to Half-Dose DOAC Route After Watchman Procedure

Use of half-dose direct oral anticoagulants (DOACs) showed promise as a long-term prophylactic strategy after successful percutaneous left atrial appendage (LAA) occlusion, according to an observational study.

Patients following this regimen (n=198) saw fewer combined clotting and major bleeding events in the first 13 months after Watchman device placement compared with peers getting standard antiplatelet therapy (n=357; 9.5% with standard vs 1.0% with half-dose DOAC; HR 9.8, 95% CI 2.3-40.7), reported Domenico Della Rocca, MD, of Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, and colleagues.

Notably, half-dose DOACs — apixaban (Eliquis; 87.9%) or rivaroxaban (Xarelto; 12.1%) in this study — were associated with reductions in thrombotic events as well as major bleeding:

• Device-related thrombosis (DRT): 3.4% vs 0% (log-rank P=0.009)
• Thromboembolic events (TEs; ischemic stroke, transient ischemic attack, peripheral thromboembolism): 3.1% vs 0.5% (log-rank P=0.046)
• Nonprocedural major bleeding: 3.9% vs 0.5% (log-rank P=0.018)

Based on the bleeding results, adoption of half-dose DOACs may offer a safety profile that beats those of full-dose DOACs or antiplatelet therapy for people with atrial fibrillation (Afib), Della Rocca’s group suggested in JACC: Cardiovascular Interventions.

Study results are “remarkable” and have potentially important clinical implications, wrote Jens Erik Nielsen-Kudsk, MD, DMSc, of Aarhus University Hospital in Denmark, in an accompanying editorial.

The half-dose DOAC strategy has patients take the usual full-dose DOAC plus aspirin in the first 45 days after LAA closure before switching to half-dose DOAC monotherapy thereafter.

The standard approach is similar in the beginning, but has Watchman patients switch to 4.5 months of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (Plavix) if the 45-day transesophageal echocardiogram is clear of device leaks or DRT, followed by aspirin monotherapy thereafter.

DRT is the major challenge of LAA occlusion. Newer devices are being designed to bring DRT down from the 3%-4% rates seen historically with the Watchman, which may present an opportunity to reduce the use of antithrombotic medications that can cause bleeding.

For instance, a newer LAA occluder, the Amplatzer Amulet, allowed the majority of patients to be discharged on DAPT.

With the second-generation Watchman FLX device, patients are recommended a full-dose DOAC plus aspirin (or DAPT) for the first 3 months and then aspirin alone for another 12 months, Nielsen-Kudsk noted.

The small FADE-DRT randomized trial is underway comparing three antithrombotic strategies after a Watchman FLX procedure.

“In the future, we will probably see new LAA closure device iterations with antithrombotic efficacy [built] into the membrane material of the devices. A local time-limited antithrombotic drug delivery until endothelialization has [been] ensured seems attractive,” the editorialist wrote.

Della Rocca and colleagues conducted a prospective study of Watchman recipients at three centers. These were 555 consecutive non-valvular Afib patients undergoing LAA closure to prevent thromboembolic events.

The cohort averaged 75 and 63% were men. Median CHA₂DS₂-VASc and HAS-BLED scores were 4 and 3, respectively. Baseline characteristics were similar between the antiplatelet and half-dose DOAC groups, the investigators said.

Transesophageal echocardiography studies were performed at 45 days, 180 days, and 365 days post-procedure. Resulting images were analyzed by two blinded physicians in each participating center.

Study authors cautioned that the non-randomized nature of their study left room for biases.

“Patients who had a high coronary risk and required long-term antiplatelet therapy and patients with renal failure or another requirement for NOAC [DOAC] dose alteration were excluded from the study. This introduces bias, as renal failure represents an independent risk factor for DRT. Also, high coronary risk patients might be particularly suitable for a DAPT based regimen,” according to Nielsen-Kudsk.

Moreover, the study’s sample was too small to compare half-dose rivaroxaban versus apixaban. Additionally, the results cannot be generalized to other occlusion devices or DOACs, Della Rocca’s group warned.

Nielsen-Kudsk recalled the safety issues with dabigatran (Pradaxa) in the RE-ALIGN trial and rivaroxaban in GALILEO.

“These NOAC studies in heart valve patients should teach us to cautiously evaluate NOACs when administered to patients with newly implanted devices in the heart,” he urged.

Moreover, the study sample was too small to compare half-dose rivaroxaban versus apixaban. Additionally, the results cannot be generalized to other occlusion devices or other DOACs, Della Rocca’s group warned.