Signals of bleeding among direct-acting oral anticoagulant users compared to those among warfarin users: analyses of the post-marketing FDA Adverse Event Reporting System (FAERS) database, 2010–2015

Figures & data

Table 1 Safety and efficacy endpoints for landmark clinical trials for studied drugs

Trials	Study drug(s)	Primary outcome	Bleeding
RE-LY^Citation16	Dabigatran 110 mg (N = 6,015), dabigatran 150 mg (N = 6,076) vs warfarin (N = 6,022)	Stroke or systemic embolism (rate per year); dabigatran (D110 [1.53%, N = 182], D150 [1.11%, N = 134]), warfarin (1.69%, N = 199)	Major bleeding (rate per year); warfarin (3.36%, N = 404), dabigatran (D110 [2.71%, N = 326], D150 [3.11%, N = 378]) Intracranial bleeding (rate per year); warfarin (0.74%, N = 89), dabigatran (D110 [0.23%, N = 28], D150 [0.30%, N = 36])
ROCKET-AF^Citation20	Rivaroxiban (N = 7,131) vs warfarin (N = 7,133)	Stroke or systemic embolism (intention-to-treat population) (rate per year); rivaroxiban (1.7%, N = 188), warfarin (2.2%, N = 240)	Major and non-major (rate per year); rivaroxiban (14.9%, N = 1,475), warfarin (14.5%, N = 1,449)
RE-MEDY^Citation42	Dabigatran 150 mg (N = 1,430) vs warfarin (N = 1,426)	Recurrent VTE; dabigatran (N = 26, 1.8%), warfarin (N = 18, 1.3%)	Major bleeding; dabigatran (N = 13, 0.9%), warfarin (N = 25, 1.8%)
RECORD I^Citation43	Rivaroxiban vs enoxaparin	DVT, pulmonary embolism; rivaroxiban (18 of 1,595, 1.1%), enoxaparin (58 of 1,558, 3.7%)	Major bleeding; rivaroxiban (6 of 2,209, 0.3%), enoxaparin (2 of 2,224, 0.1%)
RE-NOVATE (I, II)^Citation44	Dabigatran vs enoxaparin	VTE; dabigatran (114 of 1,672, 6.8%), enoxaparin (129 of 1,682, 7.7%)	Major bleeding; dabigatran (37 of 2,156, 1.7%), enoxaparin (27 of 2,157, 1.3%)
RE-COVER^Citation45	Dabigatran (N = 1,274) vs warfarin (N = 1,265)	VTE; dabigatran (N = 30, 2.4%), warfarin (N = 27, 2.1%)	Major bleeding; dabigatran (N = 20, 1.6%), warfarin (N = 24, 1.9%)
RE-MODEL^Citation46	Dabigatran (150 mg, 220 mg) vs enoxaparin 40 mg	VTE; dabigatran (D150 [213 of 526, 40.5%], D220 [183 of 503, 36.4%]), enoxaparin (193 of 512, 37.7%)	Major bleeding; dabigatran (D150 [1.3%], D220 [1.5%]), enoxaparin (1.3%)
RE-MOBILIZE^Citation47	Dabigatran (150 mg, 220 mg) vs enoxaparin 30 mg	VTE (%); dabigatran (D150 [33.7%], D220 [31.1%]), enoxaparin (25.3%)	Major bleeding; dabigatran (D150 [0.6%], D220 [0.6%]), enoxaparin (1.4%)

Abbreviations: DVT, deep vein thrombosis; VTE, venous thromboembolism.

Table 2 Demographic distribution of reports

Characteristics	Dabigatran	Rivaroxaban	Warfarin
Male	51.63%	78.05%	70.47%
Female	48.37%	21.95%	29.53%
FDA year1	2014	2015	2014
Reporting country2	US, France and Canada	US, UK and Japan	US, UK and Italy
Source of the report3	Consumers	Pharmacists	Consumers

Notes:

1 Year with the highest number of reports;

2 Countries with the highest number of reports, listed in descending order;

3 Most frequent reporting party.

Abbreviation: FDA, the US Food and Drug Administration.

Table 3 The ROR and associated 95% CIs for bleeding following dabigatran, rivaroxaban or warfarin use

Drug	Bleeding events	All ADRs	ROR	95% CI
Dabigatran	1,518	56,039	12.30	11.65–12.97
Warfarin	654	18,231	15.61	14.42–16.90
Rivaroxaban	93	2,095	18.86	15.31–23.23

Abbreviations: ADR, adverse drug reactions; ROR, reporting odds ratio.

Figure 1 Number of bleeding reports associated with each drug stratified by year.

Figure 2 Number of bleeding reports associated with each drug stratified by reporter.

Abbreviations: CN, consumer; MD, medical doctor; OT, others; PH, pharmacist.

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