• Aspirin-Free Anticoagulant Regimens Post-LAAO with Watchman Carry Less Risk – Large-Scale Registry

    Study also finds US practitioners ‘rarely’ adhere to FDA-approved antithrombotic protocol

    Patients undergoing left atrial appendage occlusion (LAAO) with the Watchman device had lower risk of adverse outcomes when discharged on warfarin or direct oral anticoagulant (DOAC) without concomitant aspirin – a step away from the U.S. approved regimen.

    This is according to a new study of the LAAO Registry, within the National Cardiovascular Data Registry (NCDR), which set out to evaluate real world postprocedural care patterns after implantation with the Watchman device, and to compare risks for different antithrombotic discharge strategies.

    The findings were published online Monday ahead of the May 10 issue of the Journal of the American College of Cardiology.

    The U.S. Food and Drug Administration (FDA) approved the Watchman LAAO device for atrial fibrillation patients (AF) in March 2015 based on two pivotal randomized controlled trials.

    LAAO is known to lower the risk of atrial fibrillation (AF)-related stroke by mechanically excluding the LAA from the systemic circulation, said the authors, led by James V. Freeman, MD, MPH, MS, from Yale University School of Medicine and Yale New Haven Health Services Corporation.

    The FDA approval included the 45-day warfarin-plus-aspirin antithrombotic regimen (maintained if a peridevice leak >5mm was found at follow-up) that had been included in the trials to minimize risk of device-related thrombosis, thromboembolism and stroke.

    The authorized regimen states that patients with no peridevice leak, or leaks of 5 mm or less at follow-up, should be switched to a dual antiplatelet therapy (DAPT) with clopidogrel and aspirin until reaching 6 months post-implantation, followed by aspirin thereafter.

    However, the authors noted several factors that lead clinicians to deviate from the standardized protocols, including data from the first 3 years of the LAAO Registry showing that U.S. patients were, in practice, “substantially older” and had higher clinically significant bleeding event rates than the trial cohorts.

    “In addition, most individuals with AF receive [DOACs], which were not approved for use at the time that the randomized trials of LAAO were designed,” said the researchers, adding that DOACs are favored for AF stroke prevention because of better safety and effectiveness vs. warfarin.

    Variation from full postprocedure treatment protocols, and the effects thereof, were previously undescribed, said the researchers.

    The current study, therefore, evaluated data from 31,994 patients who underwent successful LAAO with the Watchman device between 2016 and 2018 in the LAAO Registry, assessing adherence to the full postprocedure trial protocol, which also included standardized follow-up and imaging.

    The mean age of the cohort was 76 years, 41% were female, the mean CHA2DS2-VASc score was 4.6 and the mean HAS-BLED score was 3. Median follow-up time at first visit was 47 days, and 183 days at the second follow-up visit.

    US doctors ‘rarely’ adhere to approved anticoagulation

    U.S. practitioners “rarely” stick to the FDA-approved postprocedure treatment protocols, the researchers found – in fact, only 12.2% received the full protocol, most commonly because of deviation from antithrombotic medications.

    Still, two key components of the approved protocol – warfarin and aspirin – constituted the most common medication strategy (36.9%).

    DOAC and aspirin was the next most common (20.8%), followed by warfarin only (13.5%), DOAC only (12.3%) and DAPT (5%).

    Almost all (98.2%) were discharged on an anticoagulant and/or antiplatelet therapy. Individually, the most common discharge medications used in any regimen were aspirin (67.9%), warfarin (55.6%), DOAC (36.4%) and P2Y12 inhibitors (13.2%).

    “Although there were statistically significant differences between patients treated with the 5 mutually exclusive discharge medication regimens, owing to the size of the cohort, the absolute differences were modest except for patients treated with DAPT, who were generally older and had higher rates of comorbidities, particularly previous bleeding,” the researchers noted.

    Aspirin-free regimens carry less risk

    The adjusted risk of any adverse event through the 45-day follow-up period was significantly lower when patients were discharged without concomitant aspirin – warfarin alone (hazard ratio [HR]: 0.692; 95% confidence interval [CI]: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) vs. warfarin and aspirin.

    However, risk of readmission was higher for both warfarin (HR: 1.405; 95% CI: 1.167-1.692) and DOAC alone (HR: 1.257; 95% CI: 1.004-1.617) vs. warfarin and aspirin.

    The rates and risk of adverse events at 45 days and 6 months were compared between the most commonly used antithrombotic strategies by means of multivariable Cox frailty regression.

    Warfarin alone also retained a lower risk at the 6-month follow-up (HR: 0.814; 95% CI: 0.712-0.931) compared to warfarin and aspirin, though there were no differences among the other medication groups.

    The rate of any unadjusted major adverse event was highest among those discharged on warfarin and aspirin (4.4%), followed by DOAC and aspirin (4.3%), DAPT (4.3%), warfarin (3.3%) and DOAC (3.2%), with adverse event differences largely driven by bleeding rates.

    There were no significant differences in rates of readmission or any stroke or transient ischemic attack (TIA), or in the rate of peridevice leaks above 5 mm.

    The rate of any adverse event from discharge through 6-month follow-up was highest in those treated with warfarin and aspirin (10.3%), followed by DAPT (9.1%), DOAC and aspirin (9.1%), warfarin alone (8.5%) and DOAC (8.3%). A similar pattern was seen for any major adverse event (9.7%, 9.3%, 8.9%, 8.6% and 8%, respectively), again, largely accounted for by differences in bleeding rates.

    “Compared with the trial-studied regimen of warfarin and aspirin, discharge on anticoagulation without aspirin was associated with a lower risk of adverse events, particularly bleeding events, without evidence of increased risk of stroke/TIA or atrial or device-related thrombus,” said the researchers.

    “As LAAO devices iterate and new devices are approved, ongoing study of postprocedure antithrombotic therapy will be vital to optimize patient outcomes,” the researchers said.

    The authors list various affiliations with the Watchman device’s manufacturer, Boston Scientific.

    Continued pursual of DAPT

    In an accompanying editorial, David R. Holmes Jr, MD, from Mayo Clinic, added that a DAPT treatment approach continues to be “actively pursued” following the recent Amulet trial, and due to use of DAPT in LAAO patients in Europe and Asia, where the “indication for LAAO is a contraindication to any oral anticoagulant”.

    Although any conclusions on DAPT use from the current study would be “soft” since it was dosed infrequently during the period, the EWOLUTION registry on Watchman outcomes in real-life utilization for 1,020 patients undergoing LAAO have shown “excellent” 2-year results for DAPT, he noted.

    “These results with DAPT or even single antiplatelet agents will need to be confirmed in [randomized controlled trials].”

    Sources:

    Freeman JV, Higgins AY, Wang Y, et al. Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation. J Am Coll Cardiol 2022;79:1785-1798.

    Holmes DR, Jr. Antithrombotic Therapy After Left Atrial Appendage Occlusion: Cornucopia and Gertrude Stein. J Am Coll Cardiol 2022;79:1799-1801.

    Image Credit: Ocskay Mark – stock.adobe.com

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies. Review our Privacy Policy for more details