Key Points:
- In the PRAGUE-17 study, patients with non-valvular atrial fibrillation were treated with either oral anticoagulants or left atrial appendage closure devices and followed over a median of 3.5 years of follow-up. The primary endpoint was a composite of stroke or TIA, systemic embolism, clinically relevant bleeding, CV death, or peri-procedural/device complication.
- Treatment with left atrial appendage closure was noninferior to NOAC treatment at long-term follow-up and was associated with significantly less non-procedural bleeding.
Patients with atrial fibrillation (AF) are at elevated risk of cardioembolic stroke, and they are therefore traditionally treated with anticoagulation to ameliorate this risk. However, anticoagulation poses a considerable challenge for patients with elevated bleeding risk; in these patients, left atrial appendage closure (LAAC) devices have been used to decrease the risk of thrombus formation and decrease the necessity for anticoagulation therapy. The short-term outcomes of the PRAGUE-17 study, which compared LAAC devices with novel oral anticoagulants (NOACs), were published in 2019. At this short-term time point (with a median timepoint of 19.9 months), LAAC devices were demonstrated to be noninferior to NOACs in preventing AF-related cardiovascular, neurologic, and bleeding events. However, the long-term outcomes have yet to be determined. In a breaking presentation at the 2021 Transcatheter Cardiovascular Therapeutics (TCT) Conference today, Dr. Pavel Osmancik (Charles University and University Hospital, Prague) and his team presented the results of the PRAGUE-17 trial.
The PRAGUE-17 study (NCT02426944) was an investigator-initiated, multicenter randomized non-inferiority trial, conducted at 10 centers across the Czech Republic. Patients were treated with either a LAAC device or a NOAC. All recruited patients were required to have non-valvular atrial fibrillation and at least ONE of the following features: history of bleeding requiring hospitalization or intervention, history of cardioembolic event on anticoagulation, or CHADS-VASC score >3 and HAS-BLED score >2. Some relevant exclusion criteria included other non-AF indications for anticoagulation, presence of LA thrombus (if in LAAC group), pericardial effusion >1cm, recent bleeding or stroke (<30 days), recent ACS (<90 days), or creatinine clearance <30mL/min.
A total of 402 patients were randomized, 201 in each group. Rivaroxaban, Apixaban, or Dabigatran could be used as the NOAC, with a preference given for apixaban. Either Amulet or Watchman devices could be utilized in the LAAC arm. In the LAAC group, the default anticoagulation strategy was to receive 3 months of DAPT, followed by a TEE and de-escalation to aspirin if negative for thrombus. In high bleeding risk patients, the period of DAPT could be shortened to 6 weeks.
The primary outcome (analyzed in a modified intention-to-treat analysis) was a composite of stroke or TIA, systemic embolism, clinically relevant bleeding, CV death, or peri-procedural/device complication. Secondary analyses included analysis of each individual outcome of the composite in the primary outcome. Patients were followed for a median of 3.5 years. LAAC was noninferior for the primary outcome (8.6 vs 11.9 events per 100 patient-years, p<0.001 for noninferiority). LAAC was similarly noninferior for the secondary analyses of CV death and stroke/TIA. Non-procedural bleeding was significantly lower in the LAAC group 3.4 vs 5.9 events per 100 patient-years, p=0.038).
When discussing the implications of the study and his next steps with the Cardiology Now News team, Dr. Osmancik stated: “The question we had is whether left atrial appendage closure devices still have a role in the market and in stroke prevention…and the long-term outcomes are much more important than the short-term outcomes, because only over the long-term can you see if there is any benefit to the patient. We would like to continue to follow-up [even longer]….for another 1-2 years. Our goal is to reduce stroke rate, and I think the combination of appendage closure and NOACs would be a great trial for the future as well.”