Page 195 - Haematologica-April 2018

Major bleeding associated with oral anticoagulants
of atrial fibrillation7 and the incidence of venous throm- boembolism8 both increase with age.
The foremost complication of OAC therapy is the development of major bleeding. In the phase III random- ized clinical trials which compared warfarin and direct OAC – namely dabigatran etexilate, rivaroxaban, apixa- ban and edoxaban (DOAC hereafter) – in patients with atrial fibrillation and venous thromboembolism, this risk was reported to be 1-3% per year.9 In clinical practice some studies have reported similar risks of major bleed- ing,10-12 while others have found that it may be consider- ably higher.13,14
When DOAC were first introduced into clinical practice there was concern among clinicians that the lack of specif- ic antidotes could be detrimental to patients’ outcomes in the event of major bleeding. Recently, ‘post-approval’ observational studies have reported on the safety profile of DOAC; however, these studies have primarily focused
Table 1. Baseline characteristics by type of oral anticoagulanta.
on patients with atrial fibrillation, using patients’ clinical data obtained from national registries/databases which were designed for different purposes.15 Moreover, these studies lacked detail on the acute management of the bleeds. The burden (with respect to in-hospital mortality, morbidity and duration of hospitalization) of major bleed- ing associated with all OAC, for any clinical indications, remains largely unknown. This dearth of knowledge is true even in the case of warfarin, which has been the mainstay of OAC therapy for more than 60 years. Moreover, the widespread and increasing use of OAC, particularly in the frail elderly, underscores the urgency of comparative studies to assess the burden of major bleed- ing events associated with warfarin and DOAC. Such information should be incorporated into the clinical assessment and counseling of patients prescribed OAC, as well as the optimization of strategies for the management of OAC-associated major bleeding events.
Total patients
Female
Age (years), median[IQR] <65
65-74 75-84 ≥85
Indicationsc
Atrial fibrillation
Venous thromboembolism Mechanical heart valve Other
Prescribed anti-thrombotics Single antiplatelet therapy Dual antiplatelet therapy LMWH/UFH
Co-morbidities (type)
Congestive heart failure Hypertension
Previous stroke/TIA Liver failured
Cancer
Diabetes
Peripheral vascular disease Ischemic heart disease Chronic kidney diseased Alcohol dependence Dementia
Recurrent falls
Previous major bleeding Intracranial hemorrhagee Gastrointestinal bleed Other bleeds
Bleed history unknown
Total number (%)
2,192 (100)
1,028 (47)
80 [72-86] 284 (13) 408 (19) 863 (39) 637 (29)
1,575 (72) 456 (21) 212 (10) 184 (8)
193 (9) 27 (1) 53 (2)
342 (16) 1,181 (54) 432 (20) 35 (2) 334 (15) 494 (23) 66 (3) 570 (26) 339 (15) 48 (2) 144 (7) 128 (6)
81 (4) 87 (4) 38 (2) 626 (29)
Warfarin
1,771 (81)
814 (46)
79 [71-85] 246 (14) 348 (20) 714 (40) 463 (26)
1,265 (71) 352 (20) 211 (12) 143 (8)
144 (8) 23 (1) 47 (3)
278 (16) 949 (54) 334 (19) 28 (2) 258 (15) 402 (23) 49 (3) 456 (26) 282 (16) 39 (2) 97 (5) 94 (5)
64 (4) 71 (4) 29 (2) 513 (29)
Dabigatran
46 (2)
24 (52)
85 [79-88] 2 (4)
6 (13) 12 (26) 26 (57)
38 (83) 3 (7) --- 11 (24)
3 (7) --- 1 (2)
4 (9) 28 (61) 17 (37) 1 (2) 6 (13) 9 (20) 2 (4) 15 (33) 2 (4) 1 (2) 2 (4) 4 (9)
2 (4) 2 (4) 3 (7) 11 (24)
Rivaroxaban
283 (13)
153 (54)
82 [74-88] 29 (10) 42 (15) 96 (34) 116 (41)
193 (68) 89 (31) 1 (<1) 18 (6)
35 (12) 1 (<1) 5 (2)
46 (16) 154 (54) 56 (20) 6 (2) 55 (19) 62 (22) 13 (5) 69 (24) 49 (17) 7 (2) 35 (12) 24 (8)
11 (4) 10 (4) 6 (2) 73 (26)
Apixaban
89 (4)
35 (39)
81 [76-86] 7 (8) 12 (13) 39 (44) 31 (35)
76 (85) 11(12) --- 12 (13)
11 (13) 3 (3) ---
14 (16) 50 (56) 23 (26) ---
14 (16) 21 (24) 2 (2) 29 (33) 6 (7) 1 (1) 8 (9) 6 (7)
4 (4) 4 (4) --- 28 (31)
LMWH: low molecular weight heparin; UFH: unfractionated heparin; TIA: transient ischemic attack; aEdoxaban patients not shown separately (n=3). c10% of patients had more than one indication. dSee appendix for definitions of liver and renal failure. eIncludes two with additional non-intracranial previous bleeds
haematologica | 2018; 103(4)
739