Table 5. Incidence of major bleeding, clinically relevant non major bleeding with distribution of bleeding based on sites (cranial and gastrointestinal), fatal bleeding, mortality from VTE and all cause mortalilty of novel anticoagulants in major VTE trials.

Trial	Fatal Bleeding (Number of Subjects)	Intracranial Bleeding (Number of Subjects)	GI Bleed (Number of Subjects)	Major Bleeding N Subjects; HR; (95% CI)	Clinically Relevant non Major Bleed (Number of Subjects)	Mortality from PE or Suspected PE (Number of Subjects)	Mortality (All Cause), HR; (95% CI) (Number of Subjects)
EINSTEIN-DVT	R 2 S 5	NS	NS	R 14 (0.8%) S 20 (1.2%) 0.65 (0.33-1.30) p 0.21	R 126 (7.3%) S 119 (7.0%)	R 4 S 6	R 38 (2.2%) S 49 (2.9%) 0.67 (0.44-1.02) p 0.06
EINSTEIN- PE	R 2 S 3	R 3 (2 fatal) S 12 (2 fatal)	NS	R 26 (1.1%) S 52 (2.2%) 0.49 (0.31-0.79) p 0.003	R 228 (9.5%) S 235 (9.8%)	R 11 S 7	R 58 (2.4%) S 50 (2.1%) 1.13 (0.77-1.65) p 0.53
EINSTEIN- EXT	R 0 Pb 0	R 0 Pb 0	R 3 major + 1 minor Pb 0	R 4 (0.7%) Pb 0 p 0.11	R 32 (5.4%) Pb 7 (1.2%)	R 1 (0.2%) Pb 1 (0.2%)	R 1 (0.2%) Pb 2 (0.3%)
EINSTEIN- pooled	R 6 (0.1%) S 9 (0.2%)	R 5 (2 fatal) S 13 (4 fatal)	R 15 S 26	R 40 (1.0%) S 72 (1.7%) 0.54 (0.37-0.79) p 0.002	R 354 (8.6%) S 346 (8.4%)	R 15 (0.4%) S 13 (0.3%)	R 96 (2.3%) S 99 (2.4%)
RECORD pooled	R 1 (before receiving rivaroxaban) E NS	R 0 E 0	NS	R 14 (0.3%) E 9 (0.2%) p 0.305	R 138 (3.0%) E 115 (2.5%)	R 0 E 3 (<0.1%)	R 7 (0.2%) E 19 (0.4%) p 0.03
RE-COVER	D 1* W 1*	D 0* W 3*	D 53* W 35*	D 20 (1.6%) W 24 (1.9%) 0.82 (0.45-1.48)	NS DeductionΩ D 51 W 87	D 1 (0.1%) W 3 (0.2%)	D 21 (1.6%) W 21 (1.7%) 0.98 (0.53-1.79)
RE-COVER II	D 0* W 1*	D 2* W 2*	D 48* W 33*	D 15 (1.2%) W 22 (1.7%) 0.69 (0.36-1.32)	NS DeductionΩ D 49 W 80	D 3 (0.2%)- 2 patients died before starting dabigatran W 0	D 25 (2.0%) W 25 (1.9%) 0.98 (0.56-1.71)
RE-COVER pooled	NS	D 2 (0.1%) W 5 (0.2%) Double dummy period only: D 2 (0.1%) W 4 (0.2%)	NS	D 37 (1.4% W 51 (2.0%) 0.73 (0.48-1.11) Double dummy period only: D 24 (1.0%) W 40 (1.6%) 0.6 (0.36-0.99)	NS DeductionΩ D 99 W 166 Double dummy period only: NS DeductionΩ D 85 W 149	D 2 (0.1%) W 3 (0.1%)	D 46 (1.8%) W 46 (1.8%) 1 (0.67-1.51)
RE-MEDY	D 0* W 1*	D 2* W 4* (3 cerebral, 1 subdural)	D 5* W 8*	D 13 (0.9%)* W 25 (1.8%)* 0.52 (0.27-1.02); p 0.06	NS DeductionΩ D 67* W 120*	D 1 (0.1%) W 1 (0.1%)	D 17 (1.2%) W 19 (1.3%) 0.90 (0.47-1.72) p 0.74
RE-SONATE	D 0 Pb 0	D 0 Pb 0	D 2* Pb 0*	D 2 (0.3%) * Pb 0* HR not estimable; p 1.0	NS DeductionΩ D 34* Pb 12*	D 0 Pb 0	NS
AMPLIFY	A 1 (<0.1%); GI W 2 (0.1%); 1 GI, 1 intramuscular	A 3 (0.1%) W 6 (0.2%)	A 7 (0.3%) W 18 (0.7%)	A 15 (0.6%) W 49 (1.8%) 0.31 (0.17-0.55); p<0.001 for superiority	A 103 (3.8%) W 215 (8%)	A 12 (0.4%) W 16 (0.6%)	A 41 (1.5%) W 52 (1.9%) 0.79 (0.53-1.19)
AMPLIFY- EXT	AH 0 AL 0 Pb 0	AH 0 AL 0 Pb 1 (hemorrhagic transformation of infarct)	AH 1 (0.1%) + 7 rectal bleeds AL 3 (0.4%) + 4 rectal Pb 2 (0.2%)+ 3 rectal	AH 1 (0.1%) RR 0.25 (0.03-2.24) vs Pb AL 2 (0.2%) RR 0.49 (0.09-2.64) vs Pb RR 1.93 (0.18-21.25) vs AH Pb 4 (0.5%)	AH 34 (4.2%) AL 25 (3%) Pb 19 (2.3%) RR 0.71 (0.43-1.18) for AL vs AH	AH 3 (0.4%) AL 2 (0.2%) Pb 7 (0.8%)	AH 4 (0.5%) AL 7 (0.8%) Pb 14 (1.7%)

NS Not specified; GI = gastrointestinal; HR = hazard ratio; RR = relative risk

R = rivaroxaban; S = standard therapy; Pb = placebo; p = p value; E = enoxaparin; AH = apixaban high dose 5 mg twice daily; AL = apixaban low dose 2.5 mg twice daily; D = dabigatran; W = Warfarin; A = Apixaban; RR = Relative risk

deductionΩ = deduction from the table in the article (Number of subjects with clinically relevant non major bleeding = number of subjects with major or clinically relevant nonmajor bleeding events – number of subjects with major bleeding events)

*Number of bleeding events (rather than number of subjects with bleeding).

VTE treatment in April 2014 due to four landmark clinical trials (RE-COVER, RE-COVER II, RE-MEDY and RE-SONATE).