PROTECT AF Long Term
Long Term Results of PROTECT AF: The Mortality Effects of Left Atrial Appendage Closure Versus Warfarin For Stroke Prophylaxis in AF
Boston Scientific’s WATCHMAN™ LAAC Device Provided Statistically Superior Outcomes Over Warfarin in Primary Efficacy and All-Cause Mortality in Patients with Non-Valvular Atrial Fibrillation (AF)
PROTECT AF TRIAL BACKGROUND
- PROTECT AF was a multicenter, prospective randomized clinical trial comparing the WATCHMAN Device to long-term warfarin therapy, designed to demonstrate the treatment arm was non-inferior to the control arm.
- All randomized study patients completed follow-up assessments at post-randomization intervals of 45 days, 6 months, 9 months, 12 months and thereafter annual office visits and semi-annual telephone visits for up to 5 years.
- Patients enrolled in PROTECT AF were warfarin eligible and had a CHADS2 score of ≥1
- A total of 707 patients from 59 centers were randomized 2:1 device vs. warfarin control in the PROTECT AF trial (an additional 93 non-randomized roll-in patients were enrolled to total 800 patients).
PROTECT AF PRIMARY ENDPOINTS
- Primary Efficacy Endpoint: All stroke (ischemic & hemorrhagic), cardiovascular death (limited to any cardiovascular & unexplained death), and systemic embolism.
- Primary Safety Endpoint: Life-threatening events as determined by the Clinical Events Committee which would include events such as device embolization requiring retrieval and bleeding events e.g., pericardial effusion requiring drainage, cranial bleeding events due to any source, gastrointestinal bleeds requiring transfusion, and any bleeding related to the device or procedure that necessitates an operation.
- Previously reported PROTECT AF trial data demonstrated that the WATCHMAN LAAC device was non-inferior to warfarin control for the primary endpoint of all stroke, cardiovascular or unexplained death and systemic embolism.1
- PROTECT AF and CAP (Continued Access Protocol), a nonrandomized registry that began at the conclusion of the PROTECT AF trial that was designed to allow continued access to the WATCHMAN Device for a subset of the PROTECT AF study investigators and to gain further safety and efficacy data on the device, documented there was a learning curve associated with the LAAC procedure and with increased operator experience and enhanced training the procedure can be done safely. 2
- The enhanced training program was tested in the PREVAIL trial, a multicenter, prospective randomized clinical trial designed to confirm the results of the PROTECT AF trial and validate the safety of the implant procedure. The rate of serious vascular complications dropped significantly in both CAP (4.1%) and PREVAIL (4.4%) compared to PROTECT AF (8.7%).3
- The current dataset evaluates the long term data from the PROTECT AF trial with 4 years of follow up (mean of 45 months) with an aggregate of 2621 patient-years of follow up.
PROTECT AF LONG TERM RESULTS (4)
Primary Efficacy Endpoint: The PROTECT AF trial achieved statistical superiority for the composite endpoint of all stroke, cardiovascular or unexplained death and systemic embolism.
- The observed adverse event rate was 2.3% and 3.8% in the WATCHMAN and Control groups, respectively (RR= 0.60, posterior probability of superiority = 96%*), demonstrating a 40% relative risk reduction in the WATCHMAN group.
- All-Cause Mortality: the WATCHMAN group rates were lower versus Control: a 34% relative risk reduction in all-cause mortality in the WATCHMAN group (HR = 0.66, p=0.0379).
- Cardiovascular Mortality: the WATCHMAN group rates were lower versus Control: 1.0 per 100 patient-years for WATCHMAN and 2.4 per 100 patient-years for Control, demonstrating a 60% relative risk reduction in cardiovascular death in the WATCHMAN group (HR= 0.40, p=0.0045).
*For Bayesian analysis, posterior probabilities are used to determine superiority; ≥95% represents superiority
PROTECT AF STUDY CONCLUSION
- PROTECT AF 4-year follow-up data showed that the WATCHMAN Left Atrial Appendage Closure (LAAC) Device was statistically superior to warfarin for reducing the relative risk of the composite primary endpoint of cardiovascular death, all stroke and systemic embolization.