PROTECT AF BACKGROUND
The WATCHMAN Left Atrial Appendage Closure (LAAC) Device for Embolic PROTECTion in Patients with Atrial Fibrillation (PROTECT AF) trial was a multicenter, prospective, randomized clinical trial designed to demonstrate that WATCHMAN is non-inferior to warfarin for the combined endpoint of stroke, systemic embolism and cardiovascular or unexplained death in patients with non-valvular AF who were eligible for warfarin therapy and had a CHADS2 score of ≥1
- A total of 707 patients from 59 centers were randomized 2:1 device vs. warfarin control (an additional 93 non-randomized roll-in patients were enrolled to total 800 patients).
- 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.
The primary endpoints were as follows:
- 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*
PROTECT AF DEMOGRAPHICS
PROTECT AF RESULTS
- Previously published 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.1,2
- Previously published data from the PROTECT AF trial and CAP (Continued Access Protocol) registry documented a learning curve associated with the LAAC procedure3. Subsequent trials (PREVAIL) have shown an improved implant profile in both new and experienced operators, demonstrating the success of our physician training program4.
The PROTECT AF trial results below reflect WATCHMAN and warfarin performance at a mean follow-up of 3.8 years or 2621 patient years. These results have been published in the peer-reviewed Journal of American Medical Association (JAMA).
- PROTECT AF five year results (2717 patient years) were presented by Dr. Vivek Reddy at the 2014 TCT Conference and can be accessed via TCTMD here.
Primary Efficacy Endpoint: the WATCHMAN group was superior to warfarin: 2.3% for WATCHMAN and 3.8% for warfarin annually, demonstrating a 40% relative risk reduction for the composite endpoint of all stroke, cardiovascular or unexplained death and systemic embolism (RR=0.60, posterior probability of superiority 96%**)
HR indicates hazardous ratio; RR indicates rate ratio.
Additional 4-Year Results:
- All Stroke: the WATCHMAN group was non-inferior to warfarin: 1.5% for WATCHMAN and 2.2% for warfarin annually, demonstrating a relative risk reduction of 32% of all stroke in the WATCHMAN group (RR=0.68, posterior probability of non-inferiority = 99%**)
- Cardiovascular Mortality: the WATCHMAN group was superior to warfarin: 1.0% for WATCHMAN and 2.4% for warfarin annually, demonstrating a 60% relative risk reduction in cardiovascular death in the WATCHMAN group (RR= 0.40, posterior probability of superiority = 99%**, p=0.0045).
- All-Cause Mortality: the WATCHMAN group was superior to warfarin**: 3.2% v. 4.8% annually in favor of WATCHMAN, demonstrating a 34% relative risk reduction in all-cause mortality in the WATCHMAN group (HR=0.66, p=0.04).
- Hemorrhagic Stroke: the WATCHMAN group was superior to warfarin: 0.2% for WATCHMAN and 1.1% for warfarin annually, demonstrating a relative risk reduction of 85% of hemorrhagic stroke in the WATCHMAN group (RR=0.15, posterior probability of superiority = 99%**)
- Disabling Stroke: the WATCHMAN group was superior to warfarin: 0.5% for WATCHMAN and 1.2% for warfarin annually demonstrating a relative risk reduction of 63% of disabling strokes in the WATCHMAN group (RR=0.37, posterior probability of superiority = 98%**)
*For Bayesian analysis, a posterior probability of 97.5% represents non-inferiority; ≥95% represents superiority
**Statistical superiority of all-cause mortality was not maintained out to the PROTECT AF 5 year follow-up, as presented by Dr. Vivek Reddy at TCT 2014