Thank you very much. As Jackie said, I'm going to be talking about antithrombotic regimen after left atrial appendage occlusion. This is, I think, probably an under-recognized but really important opportunity to improve the morbidity and mortality after this procedure and the effectiveness in terms of mitigating bleeding risk over the long term. We know that there's good data showing that rates of bleeding are very commonly the indication for placement of a left atrial appendage occlusion device and that the rates of bleeding after this procedure remain not insubstantial. But we need some kind of antithrombotic therapy to prevent device-related thrombus in the first few months. So we'll talk about the data for what to do. The Watchman trials included a pretty complex discharge antithrombotic protocol. So patients were to be discharged on morphine and aspirin. They had to have a follow-up visit of 45 days for the transencephalogelic cardiogram at that time. If they had a residual leak of zero to five millimeters and no left atrial appendage thrombus, they discontinued warfarin and initiated dual antiplatelet therapy. If there was a leak greater than five millimeters or an atrial thrombus, they continued warfarin through six months and had repeat imaging. For those that were transitioned to DAPT, they stayed on that for another four and a half months through the six-month mark and then went down to aspirin only. So a pretty complex regimen. We did a study using the NCDR LAO registry. This is a registry of the vast majority of procedures performed in the United States. What we found is that only about 12% of patients were treated with the full FDA-approved discharge treatment protocol. By far the most common deviation from this protocol was the discharge medication regimen. At that time, which was during the first-generation Watchman 2.5 era, it was pretty common for patients to be on warfarin and aspirin, about 35% of patients. But the rest of patients were on other strategies, including anticoagulation only, DOAC plus aspirin, DOAC alone, or DAPT. We then went on to look at these different antithrombotic strategies and the association of that with adverse events through the 45-day to eight-week mark. What we found actually was that anticoagulation alone without aspirin was associated with the lowest risk of major adverse events or any adverse event, and this was largely driven by a decreased risk of bleeding. DOAC and aspirin or warfarin and aspirin were very comparable. I think that opened everyone's eyes to the notion that DOAC was, in fact, a very reasonable alternative to warfarin. Then in our study, dual antiplatelet therapy again looked fairly comparable to anticoagulation plus aspirin. I think this was kind of a first insight into different strategies that are being utilized in the real world, and that in general these are fairly comparable, though maybe a potential safety advantage to using anticoagulation alone, at least through that first two-month period. The pinnacle FLEX study, which then was looking at the Watchman FLEX, the second-generation device, had a protocol where patients were discharged on DOAC and aspirin for 45 days and then transitioned to DAPT for four and a half months. This showed favorable outcomes compared with prior randomized trials. I think, again, confirmed this notion that DOAC and aspirin was at least as good as warfarin and aspirin and a viable alternative to warfarin and aspirin on discharge. In terms of dual antiplatelet therapy, as I said, initial study in the Watchman 2.5 era looked favorable for DAPT relative to anticoagulation plus aspirin. A dedicated DAPT NCDR-LAO registry study in the FLEX era showed comparable results of DAPT versus anticoagulation plus aspirin, with most patients actually having DOAC plus aspirin. I think this really confirmed those findings over two different devices and over a long period of time that DAPT was a reasonable alternative. Based on this, the indications for using DAPT after Watchman FLEX implant were included, so it became acceptable to use anticoagulation plus aspirin or DAPT with the Watchman FLEX device. The pivotal amulet IDE study included most patients who were discharged on dual antiplatelet therapy after amulet. The outcomes were comparable to Watchman with most of the Watchman patients being discharged on anticoagulation plus aspirin. So I think, again, this confirmed our initial findings from the NCDR-LAO registry that DAPT is probably very comparable to anticoagulation plus aspirin, and that's the data we have thus far for amulet. There are a number of ongoing left atrial appendage closure randomized trials with different post-procedural anti-thrombotic regimen, and the first of those is the OPTION trial. It's a study of patients who are status post AFib ablation and left atrial appendage occlusion with the Watchman FLEX device, and patients in this study were discharged on Doac or Warfarin and aspirin, and now, though, just for three months, and then after the three-month period are transitioned to aspirin. So this dramatically simplifies the regimen, and I think it raises the issue that not only do we need to think about what anti-thrombotic drugs we're using, but the duration of those drugs that's optimal to kind of mitigate the risk of DRT and ischemic events in the brain and thrombotic events, but also mitigate the risk of bleeding. The CHAMPION trial, which was a trial of Watchman FLEX versus Doac, included a discharge treatment strategy of Doac plus aspirin or DAPT, and then actually, midway through the study, they allowed for Doac alone based on our initial findings, and so I think that will also offer a lot of insight into these three different discharge treatment strategies. Again, they went for a three-month time horizon rather than the six-week time horizon with then a transition to DAPT at six weeks based on TE and anti-thrombotics that were intensive through the six-month time horizon, so I think trying to shorten up to that three-month time horizon, I think, is the theme here. Similarly, CATALYST was Amulet versus Doac, and that's another large trial with a discharge treatment strategy of dual antipollutant therapy for three months, so again, shorten things up to three months. A number of smaller trials as well that I probably won't get into the details of today, but I think we have a number of trials that are coming down the pipeline that will offer a great deal of insight in this space. So, in conclusion, studies to date are insufficient to define the optimal post-procedure anti-thrombotic strategy, but what we know is that anticoagulation plus aspirin is well-established for WATCHMIN, and that includes either Doac plus aspirin or Warfarin plus aspirin, with Doac plus aspirin being far more common in use, at least in the United States right now. There's increasing evidence for DAPT and Doac alone for WATCHMIN, and actually decent data, and we are just about to present more data at HRS on the notion that anticoagulation alone with a Doac may be the optimal strategy for mitigating bleeding risk. DAPT for Amulet is very well-established, and future studies will provide more insight on optimal treatment regimen, and then, importantly, the duration of therapies that are safe, with a lot of studies looking to shorten up the time arising for intensive antithrombotics to three months. Thank you very much.

antithrombotic regimen

left atrial appendage occlusion

device-related thrombus

anticoagulation

dual antiplatelet therapy