Li (2018)

Retrospective Cohort

(n = 80,279)

Apixaban 2.5, 5 mg vs. warfarin respectively

Apixaban 5 mg

68.6 + 11

Apixaban 2.5 mg 82.5 + 9.5

Apixaban 5 mg BID associated with lower risk of major bleeding (HR: 0.59, 95% CI: 0.53 - 0.66). Apixaban 2.5 mg BID is also associated with a lower risk of major bleeding (HR: 0.59, 95% CI: 0.49 - 0.71) [14] .

Siontis (2019)

Retrospective Cohort

(n = 25,523)

NVAF and ESKD

Apixaban vs. warfarin

68.22 + 11.89

Apixaban was associated with significantly less bleeding (HR 0.72, 95% CI 0.59 - 0.87; P < 0.001) [15]

Janssen Scientific Affairs, LLC

(2016)

PIONEER AF-PCI

RCT

(n = 2,124)

Group 1: Rivaroxaban 15 mg daily plus P2Y12

Group 2: Rivaroxaban 2.5 mg twice daily followed by rivaroxaban 15 mg daily plus low-dose aspirin.

Group 3: Warfarin plus DAPT followed by warfarin plus low-dose aspirin.

70.1 ± 8.97

Incidence of clinically significant bleeding: 16.8% of group 1 vs. 18.0% of group 2 vs. 26.7% of group 3 (HR 0.59, 95% CI 0.47 to 0.76; P < 0.001 for group 1 vs. 3; HR 0.63, 95% CI 0.5 to 0.8; P < 0.001 for group 2 vs. 3).

Incidence of major bleeding (secondary outcome):

2.1% of group 1 vs. 1.9% of group 2 vs. 3.3% of group 3 (HR 0.66, 95% CI 0.33 to 1.31; P = 0.234 for group 1 vs. 3; HR 0.57, 95% CI 0.28 to 1.16; P = 0.114 for group 2 vs. 3)

Janssen Scientific Affairs, LLC

(2010)

NCT00403767

RCT

(n = 14,269)

Rivaroxabanvswarfarin

71.2 ± 9.42

Composite event of major/non-major bleeding events of rivaroxaban vs. warfarin were similar: 0.21% vs. 0.20% (HR 1.03; 95% CI 0.96 to 1.11, P = 0.442).

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

Major Bleeding:

Group 1: 2.99%/YR (HR 0.80; 95% CI 0.70 to 0.93, P = 0.0026)

Group 2: 3.55%/YR (HR 0.93; 95% CI 0.81 to 1.07, P = 0.3146)

Group 3: 3.81%/YR.

Bristol-Myers Squibb (2011)

ARISTOTLE

NCT00412984

RCT

(n = 18,201)

Apixaban (2.5, 5 mg) vs warfarin (INR 2 - 3)

69.1 ± 9.68

Rate of major bleeding for apixaban was 2.13%/yr compared to warfarin, 3.09% (HR 0.69; 95% CI 0.80 to 0.99, P < 0.001).

Bristol-Myers Squibb (2018)

NCT02415400

RCT

(n = 4,614)

Apixaban + ASA or placebo vs warfarin + ASA or placebo

69.9 ± 9.17

Major or clinically relevant bleeding:

Apixaban 24.66%/yr demonstrated superiority vs warfarin 35.79%/yr (HR 0.69; 95% CI 0.58 to 0.82, P < 0.0001).

ASA as adjuvant showed increase bleeding risk: 40.51%/yrvs placebo matching ASA 21.03% (HR 1.88; 95% CI 1.58 to 2.23, P < 0.0001).