		Randomized cohort trial (n = 27,298)	Rivaroxaban vs. apixaban			Rivaroxaban 72.7 ± 11.08 Apixaban 72.7 ± 11.66	Rate of stroke/SE was 2.65/100 person-years for the apixaban group vs. 2.31/100 person-years for the rivaroxaban group (HR 1.00; 95% CI 0.89 - 1.14) [13] .
Li (2018)		Retrospective Cohort (n = 80,279)	Apixaban 2.5,5mg vs. warfarin respectively			Apixaban 5 mg 68.6 ± 11 Apixaban 2.5 mg 82.5 ± 9.5 Warfarin (5 mg matched) 69.2 ± 11.7 Warfarin (2.5 mg matched) 80.1 ± 8.5	Apixaban 5 mg BID associated with lower risk of stroke/SE ([HR]: 0.70, 95% [CI]: 0.60 - 0.81). Apixaban 2.5 mg BID is also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49 - 0.81) [14] .
Siontis (2019)		Retrospective Cohort (n = 25,523)	NVAF and ESKD Apixaban vs. warfarin			68.22 ± 11.89	No difference in risk of stroke (HR 0.88, 95% CI 0.69 - 1.12; P = 0.29) [15] .
Bristol-Myers Squibb (2017) AVERROES NCT00496769		RCT (n = 5,598)	Apixaban (2.5, 5 mg) vs ASA (81-324 mg)			69.9 ± 9.58	Apixaban demonstrated superiority vs ASA; 1.62%/Year vs 3.63%/Year (HR 0.45; 95% CI 0.32 to 0.62, P < 0.001) in stroke/systemic embolism prevention, respectively. Episodes of major bleeding: apixaban 1.4%/Year, and ASA 1.2%/Year (HR 1.13; 95% CI 0.74 to 1.75; P = 0.57).
Bristol-Myers Squibb (2018) NCT02415400		RCT (n = 4,614)	Apixaban + ASA Apixaban + placebo Warfarin + ASA Warfarin + placebo			69.9 ± 9.17	Apixaban (15.85%/yr) vs warfarin (17.17%/yr) with placebo were similar is stroke prevention (HR 0.92; 95% CI 0.75 to 1.13, P = 0.4370). Adjuvant therapy with ASA (15.28%/yr) vs placebo (17.73) did not show significance (HR 0.86; 95% CI 0.70 to 1.07, P = 0.1742).
Boehringer Ingelheim (2009) RE-LY NCT00262600		RCT (n = 5,883)	Group 1: Dabigatran 110 mg PO BID Group 2: Dabigatran 150 mg PO BID Group 3: Warfarin (INR 2 - 3)			71.5 ± 8.7	Group 1 NI vs. group 3 (HR 0.90; 95% CI 0.74 to 1.10, P < 0.0001) in stroke prevention. Group 2 NI vs. group 3 (HR 0.65; 95% CI 0.52 to 0.81, P < 0.0001) in stroke prevention. Group 2 met superiority vs. group 3 in reducing stroke or systemic embolism (HR 0.83; 95% CI 0.74 to 0.93, P = 0.0015).
Watchman^TM Device and incidence of stroke
Holmes, D. R. et al. (2015) (PROTECT AF) (PREVAIL) (CAP) (CAP2)		Meta-Analysis (n = 2,406) (PROTECT AF n = 707) (PREVAIL n = 407) (CAP n = 566) (CAP2 n = 579)		Watchman vs Warfarin		PROTECT AF 72.0 ± 8.9 PREVAIL 74.3 ± 7.4 CAP 74.0 ± 8.3 CAP2 75.3 ± 8.0	NVAF at increased risk for stroke or bleeding. LAAC resulted in improved rates of hemorrhagic stroke, cardiovascular/unexplained death, and nonprocedural bleeding compared to warfarin. Watchman device had fewer hemorrhagic strokes (0.15 vs. 0.96 events/100 patient-years [PY]; hazard ratio [HR]: 0.22; 95% CI: 0.08 to 0.61; P = 0.004), cardiovascular/unexplained death (1.1 vs. 2.3 events/100 PY; HR: 0.48; 95% CI: 0.28 to 0.81; P = 0.006), and nonprocedural bleeding (6.0% vs. 11.3%; HR: 0.51; 95% CI: 0.33 to 0.77; P = 0.006) compared with warfarin. All-cause stroke or systemic embolism was similar between both strategies (1.75 vs. 1.87 events/100 PY; HR: 1.02; 95% CI: 0.62 to 1.7; P = 0.94). There were more ischemic strokes in the device group (1.6 vs. 0.9 and 0.2 vs. 1.0 events/100 PY; HR: 1.95 and 0.22, respectively; P = 0.05 and 0.004, respectively) [16] .
Koifman, E. et al. (2016)		RCT (n = 212)		Watchman Device vs Warfarin Therapy		75 ± 8	14 studies with 246,005 patients were included in the analysis, among which 124,823 were treated with warfarin, 120,450 were treated with NOACs and 732 had Watchman implanted. Mean age was 72 ± 9 years, 53% were male, and mean CHADS2 score was 2.1 ± 1.6. Both NOACs and Watchman were superior to warfarin in hemorrhagic stroke prevention (OR = 0.46 [0.30 - 0.82] and OR = 0.21 [0.05 - 0.99], respectively). NOACs significantly reduced total stroke (OR = 0.78 [0.58 - 0.96]) and major bleeding (OR = 0.78 [0.65 - 0.91]) compared with warfarin. Indirect comparison between NOAC and Watchman revealed no significant differences in outcomes, though there was a trend toward higher rates of ischemic stroke with Watchman compared with NOAC (OR 2.60 [0.60 - 13.96]) with the opposite findings with hemorrhagic stroke (OR = 0.44 [0.09 - 2.14]) [17] .
Pahlajani, Dev et al. (2016)	Meta Analysis (n = 2406)		Watchman Device vs Warfarin Therapy		71.2 + 9.42		With mean follow-up of 2.69 years, patients receiving LAAC with the Watchman device had significantly fewer hemorrhagic strokes (0.15 vs. 0.96 events/100 patient-years [PY]; hazard ratio [HR]: 0.22; P = 0.004), cardiovascular/unexplained death (1.1 vs. 2.3 events/100 PY; HR: 0.48; P = 0.006), and nonprocedural bleeding (6.0% vs. 11.3%; HR: 0.51; P = 0.006) compared with warfarin. All-cause stroke or systemic embolism was similar between both strategies (1.75 vs. 1.87 events/100 PY; HR: 1.02; 95% CI: 0.62 to 1.7; P = 0.94). There were more ischemic strokes in the device group (1.6 vs. 0.9 and 0.2 vs. 1.0 events/100 PY; HR: 1.95 and 0.22, respectively; P = 0.05 and 0.004, respectively). Both trials and registries identified similar event rates and consistent device effect in multiple subsets (refer to Figure 5) [16] .