Introduction
Methods
Definitions
Data sources and eligibility criteria
Abstract screening
Full-text screening, data extraction and quality review
Data synthesis
Results
Study type, country and comparator population
Patient age and common health outcomes
Authors and publication year | Objective/aim | Study type | Country/study time frame | DOAC (s) examined (number of patients by drug) | Comparison population(s) | Population and sample size |
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Bruckbauer et al. 2019 [48] | To assess the impact of DOAC intake compared with coumadin (COU) in hip fracture (HF) patients | Retrospective cohort | Salzburg, Austria Jan 2015–May 2017 | Any DOAC (n = 13 dabigatran, n = 34 rivaroxaban, n = 7 apixaban) | 1. COU 2. no antithrombotic therapy (no-ATT) | Patients ≥ 65 years with a median age of 83.5 years [range 76–89] n = 54 DOAC; n = 59 COU; n = 207 no-ATT |
Cafaro et al. 2019 [49] | To establish TTS among non-anticoagulated and anticoagulated patients taking either vitamin K antagonist (VKA) or DOACs | Retrospective cohort | Canada, 1 July 2016–31 Dec 2017 | Any DOAC (n = 6 dabigatran, n = 21 apixaban, n = 4 rivaroxaban) | 1. VKA 2. no anticoagulant | Patient inclusion was age ≥ 18 years, but mean age was 84 years [range 29–98] n = 31 DOAC; n = 28 VKA; n = 413 no anticoagulant |
Creeper et al. 2020 [50] | To investigate the effect of DOAC therapy on time to surgery and patient outcomes, and to explore the impact of different pre-operative protocols on surgical delay | Retrospective cohort | Australia, 1 Jan 2017–31 Dec 2017 | Any DOAC (n = 8 dabigatran, n = 44 apixaban, n = 29 rivaroxaban, n = 1 edoxaban) | 1. Warfarin 2. antiplatelets 3. dual anticoagulation and antiplatelet 4. no anticoagulation or antiplatelet | Patient inclusion age was not specific, but median age was 84 years [interquartile range: 76–89] n = 82 DOACs; n = 63 warfarin; n = 366 antiplatelets; n = 13 dual anticoagulation and antiplatelet; n = 714 no anticoagulation or antiplatelets |
Daugaard et al. 2019 [47] | To examine if pre-operative antithrombotic treatment was associated with increased use of blood transfusion and 30-day mortality following hip fracture surgery | Retrospective cohort | Denmark, 1 Jan 2005–31 Dec 2016 | Any DOAC—both current (i.e., at least one prescription ≤ 90 days prior to surgery) and former (i.e., redemption of one prescription 91–365 days prior to surgery) users (unspecified number by DOAC type) | 1. VKA; 2. antiplatelets including acetylsalicylic acid; 3. non-user of DOACs in the year prior to surgery | Patients ≥ 65 years. Mean age not specified n = 1063 DOAC, n = 4162 VKA, n = 24,567 antiplatelets; n = 73,507 non-DOACs |
Franklin et al. 2018 [37] | To evaluate the pre-hospital use of DOACs on the outcomes of early surgical fixation of geriatric HF | Retrospective case–control | US, 2010–2015 | Any DOAC (n = 6 rivaroxaban, n = 5 apixaban n = 8 dabigatran) | 1. Controls (unspecified criteria, but excluded patients on plavix or coumadin or > 81 mg of daily aspirin) matched on age ± 3 years, sex, and operation type (i.e., hemiarthroplasty, cephalomedullary nail (CMN), sliding hip screw | Patients aged 60–89 years who underwent HF surgery within 48 h of admission. Mean age not specified n = 19 DOACs n = 76; controls |
Frenkel Rutenberg et al. 2018 [51] | To assess outcomes of patients treated with VKAs or DOACs undergoing surgical treatment for fragility HF | Retrospective cohort | US, Jan 2012–Jun 2016 | Any DOAC (n = 18 dabigatran, n = 16 rivaroxaban, n = 13, apixaban) | 1. VKAs 2. no-anticoagulation | Patients > 65 years with a mean age ~ 82 years n = 47 DOACs; n = 103 VKAs; n = 646 no anticoagulation |
Gosch et al. 2020 [52] | To compare the short-term outcome of older hip fracture patients without oral anticoagulation, VKAs and DOACs | Retrospective case–control | Germany, Feb 2017–Jun 2018 | Any DOAC (unspecified DOAC type) | 1. No anticoagulants 2. VKA | Patients > 70 years Patient mean age was 83.9 years n = 26 DOACs, n = 15 VKA; n = 61 no anticoagulants |
Hourston et al. 2020 [42] | To assess whether HF patients admitted on Warfarin or DOACs were at risk of operative delay, prolonged LOS, or increased mortality | Retrospective cohort | UK, Oct 2014–Dec 2016 | Any DOAC (n = 19 rivaroxaban, n = 8 apixaban, n = 5, dabigatran) | 1. No anticoagulants 2. Warfarin | Inclusion age unspecified Patient mean age was 85 years n = 32 DOAC, n = 83 warfarin, n = 729 no anticoagulants |
King et al. 2020 [38] | To investigate the effect of DOACs on patient outcomes receiving early (< 48 h) versus delayed (> 48 h) HF surgery | Retrospective cohort | Queensland, Australia; Jan 2012–Dec 2017 | Any DOAC (n = 5 apixaban, n = 8 dabigatran, n = 15 rivaroxaban) | 1.No DOACs matched to TTS < 48 h on age, ASA grade, sex, surgery type (i.e., arthroplasty vs. other fixation), time to surgery (< 48 h) and dementia status | Inclusion age unspecified Mean age ~ 84 years n = 28 DOAC (n = 17 early surgery and n = 11 late surgery), n = 56 no DOACs |
Leer Salvesen et al. 2020 [43] | To determine whether DOAC users have delayed HF surgery compared to non-DOAC users and whether hospital LOS, mortality, re-operations and bleeding complications were influenced by use of DOACs | Retrospective cohort | Norway, Dec 2016–Dec 2017 | Any DOAC (unspecified number by DOAC type) | 1. No anticoagulants | Patients aged > 60 years, with a mean age of 82.1 years n = 47 DOACs; n = 267 no anticoagulants |
Lott et al. 2019 [12] | To evaluate whether patients with HFs receiving platelet aggregation inhibitors (PAI) and DOACs treated within 48 h of admission had worse surgical and clinical outcomes than those whose surgery was delayed > 48 h | Retrospective cohort | US, Oct 2014–Sep 2016 | Any DOAC (n = 4 dabigatran, n = 10 rivaroxaban, n = 15 apixaban) | 1. PAI including clopidogrel and aspirin | Patients ≥ 55 years. However, mean age was ~ 83 years n = 29 DOACs; n = 49 PAI (n = 38 clopidogrel; n = 11 aspirin) |
Mahmood et al. 2021 [40] | Review whether taking PAIs or anticoagulants was associated with increased mortality for HF patients; and to evaluate the mortality and complication rates for patients taking these agents who underwent early (< 24 h) surgery | Retrospective cohort | UK, Jan 2016–Jan 2019 | Any DOAC (unspecified number by DOAC type) | 1. Control group (no PAI or anticoagulants 2. PAI (i.e., aspirin or clopidogrel) 3. Warfarin | Patients aged ≥ 60 years with a mean age of 82.1 years n = 69 DOACs; n = 617 controls; n = 260 PAI; n = 92 warfarin |
Mullins et al. 2018 [26] | To determine whether not waiting for the elimination of DOACS has an effect on the amount of peri-operative bleeding in HF patients | Retrospective case–control | UK, Jan 2015–March 2017 | Any DOAC (n = 14 apixaban, n = 5 dabigatran, n = 44 rivaroxaban) | 1. Patients not taking DOACs or warfarin (matched on age ± 5 years, sex, operation, American Society of Anesthesiologists (ASA) grade | Patients aged ≥ 60 years with a mean age of 85 years n = 63 DOACs; n = 62 no DOACs |
Rostagno et al. 2021 [41] | To investigate the effects of ongoing treatment with DOACs on TTS and on in-hospital clinical outcomes in patients with HF | Retrospective case–control | Italy, Jan 2016–Jan 2019 | Any DOAC (n = 28 dabigatran, n = 19 rivaroxaban, n = 24 apixaban, n = 3 edoxaban) | 1. Patients not taking anticoagulants (matched on age, sex, fracture type, ASA grade | Elderly patients, age unspecified. Mean age was ~ 84 years n = 74 DOACs; n = 206 no-anticoagulants |
Saliba et al. 2020 [44] | Assess the association between pre-operative DOACs use and adverse outcomes in elderly patients with HF | Retrospective cohort | Israel, 1 Jan 2014–31 Dec 2018 | Any DOACs (n = 129 apixaban, n = 71 rivaroxaban, n = 47 dabigatran) | 1. VKAs 2. no anticoagulants | Patients ≥ 65 years with a mean age of 82.2 years n = 247 DOACs; n = 163 VKAs; n = 3,008 no anticoagulants |
Scherman et al. 2019 [45] | To compare estimates of peri-operative blood loss and mortality between HF patients taking DOACs and no anticoagulation | Retrospective cohort | Israel, 2011–2016 | Any DOAC (apixaban, rivaroxaban and dabigatran, unspecified number by DOAC type) Could have concurrent use of aspirin and PAI (clopidogrel, prasugrel, ticagrelor) | 1. control with no anticoagulant use 2. Coumadin | Patients ≥ 65 years who had closed reduction internal fixation (CRIF) or hemiarthroplasty (HA) with a mean age ~ 82 years n = 89 DOACs; n = 1,466 no anticoagulation; n = 159 coumadin (n = 18 DOACs taking aspirin and n = 5 taking clopidogrel) |
Schuetze et al. 2019 [46] | To determine the effect of DOACs on HF patients which received a proximal femur nail anti-rotation (PFNA) within 24 h after trauma | Retrospective cohort | Germany, Jan 2013– Dec 2017 | Any DOACs (unspecified number by DOAC type) | (1) no anticoagulation; (2) acetylsalicylic acid (ASS); (3) PAI; (4) VKA | Patients of all ages, but mean age was 80.7 years n = 52 DOACs; n = 146 no anticoagulation; n = 74 ASS; n = 30 PAI; n = 25 VKA |
Shani et al. 2021 [53] | To investigate if patients treated with DOACs have delayed HF surgical compared to patients on no anticoagulants or Warfarin, and if there is an impact on TTS, LOS and mortality | Retrospective cohort | Israel, 1 Jan 2014–31 Dec 2017 | Any DOAC (unspecified number by DOAC type) | 1. No oral anticoagulant; 2. warfarin | Patients > 65 years with a mean age of ~ 83 years n = 415 DOACs; n = 5,102 no anticoagulants; and n = 311 warfarin |
Tarrant et al. 2020 [39] | To investigate how DOACs affect surgical timing and peri-operative outcomes | Retrospective case–control | Australia; 2011–2018 | Any DOACs (n = 56 apixaban, n = 18 dabigatran, n = 38 rivaroxaban) | 1. control group not taking antithrombotic medication and matched on age, sex, and year of admission | Patients aged ≥ 65 years, with a mean age of 84.3 years n = 112 DOACs; n = 112 controls |
Tran et al. 2015 [54] | To determine how anticoagulation with VKA or DOAC affects TTS | Case–control | Canada, 1 Jan 2010–24 March 2014 | Any DOAC (n = 22 dabigatran, n = 4 rivaroxaban, n = 1 apixaban) | 1. VKAs 2. no anticoagulants matched on age and sex | Age inclusion criteria not specified, but median age 86 years n = 27 DOACs; n = 260 no anticoagulants; n = 233 VKAs |
Viktil et al. 2019 [55] | To determine serum concentrations and elimination rates of DOACs in HF patients and TTS | Prospective cohort pilot study | Oslo, Norway (6-month period, dates unspecified) | Any DOAC (n = 2 dabigatran, n = 3 rivaroxaban, n = 6 apixaban) | 1. Warfarin 2. PAI | Patients ≥ 65 years, with a median age 84 years (n = 11 DOACs; n = 14 warfarin; n = 50 PAI) |
Authors and publication year | Blood loss definition | Time to surgery definition | Type of anaesthesia | Hours prior to surgery DOACs ceased | Use of reversal agents | Health outcome(s) examined (primary and secondary outcomes) | Study findings (primary and secondary) |
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Bruckbauer et al. 2019 [48] | Drainages from intensive care unit (ICU) admission to discharge | Time from admission to surgery | NR | NR | Specified in secondary study findings | Primary: (1) transfusion requirements; (2) post-operative bleeding rate Secondary: (1) time to surgery (TTS); (2) use of reversal agents; (3) intensive care unit (ICU) length of stay (LOS); (4) mortality | Primary: (1 and 2) no difference in blood less through drainages for DOAC or COU Secondary: (1) TTS longer for DOAC group: 37% on DOACs, 51% on COU, and 55% no-ATT had surgery within 24 h (2) Reversal agents: 78% on COU received vitamin K and 4 patients received PCC One patient on DOAC received prothrombin complex concentrate (PCC) and one patient on dabigatran received idarucizumab (3) No differences in ICU LOS (4) No differences for in-hospital mortality |
Cafaro et al. 2019 [49] | International Society on Thrombosis and Haemostasis (ISTH) Any major bleeding from presentation to discharge including surgical bleeding Pre-operative major bleeding limited to the pre-operative period | Time from hospital admission to surgery | NR | NR | Peri-operative use of PCC, vitamin K, idarucizumab and/or plasma, unspecified further | Primary: (1) TTS Secondary: (1) surgical delay; (2) hospital LOS; (3) acute venous thromboembolism (VTE), pulmonary embolism PE); (4) any major bleeding and pre-operative major bleeding; (5) stroke; (6) in-hospital mortality | Primary: (1) Median TTS was longer in VKA (64 h) and DOAC (61 h) vs. no anticoagulant (44 h). No difference in TTS for VKA (64 h) vs. DOAC (61 h) Secondary: (1) No VKA and 39% of DOACs had surgery within 48 h vs. 60% no anticoagulant (2) Similar LOS for VKA, DOAC and no anticoagulant; 15.6, 16.1, 16.6 days, respectively (3) No difference in VTE or PE for no anticoagulant, VKA or DOAC (4) No difference in any major bleeding for DOAC (80.0%) vs. VKA (75.0%) vs. no anticoagulant (84.9%) Pre-operative major bleeding higher in DOAC (24.0%) vs. VKA (14.2%) vs. no anticoagulant (10.0%) (5) No difference in stroke between groups (6) No difference in in-hospital mortality for DOAC (6.5%), VKA (7.1%) and no anticoagulant (3.4%) |
Creeper et al. 2020 [50] | Change in haemoglobin (Hb) (g/L) defined as the difference between the maximum recorded Hb level up to 48 h pre-operatively to the minimum level recorded within 72 h post-operatively | Time of first presentation to any hospital (regardless of location and ability to perform correctional surgery) to the time of operation | NR | NR | NR | Primary: (1) TTS Secondary: (1) post-operative change in haemoglobin; (2) transfused packed red blood cell units 2 days pre-operatively to 3 days post-operatively; (3) 30-day mortality | Primary: (1) median TTS was longer for DOAC (43.9 h) vs. warfarin (27.9 h) and TTS for DOACs vs. other comparator populations was not conducted Secondary: (1) there was no difference in change in haemoglobin between DOAC vs. warfarin and change in haemoglobin for DOACs vs. other comparator populations was not conducted (2) There was no difference in transfusion requirements between DOAC vs. warfarin and transfusion requirements for DOACs vs. other comparator populations was not conducted (3) There was no difference in 30-day mortality for DOAC vs. warfarin and comparison of 30-day mortality for DOACs vs. other comparator populations was not conducted |
Daugaard et al. 2019 [47] | NR | Time from hip fracture admission to surgical procedure | NR | NR | NR | Primary: (1) red blood cell transfusion within 7 days (2) 30-day mortality Secondary: (1) transfusion and TTS; (2) 30-day mortality and TTS | Primary: (1) compared to non-DOAC users, current DOAC users had a 7% higher adjusted relative risk of a blood transfusion and former DOAC users had no higher transfusion risk (2) Compared to non-DOAC users, both current and former DOAC users had no higher risk of mortality Secondary: (1) compared to non-DOAC users, current DOAC users who had surgery < 24 h had a 14% higher risk of a blood transfusion, and there was no difference for current DOAC users who had surgery between 24 and 36 h or > 36 h. There was no difference for former DOAC users that had surgery < 24 h, between 24-36 h or > 36 h compared to non-DOAC users (2) Compared to non-DOAC users, current and former DOAC users who had surgery < 24 h, between 24 and 36 h or > 36 h. Did not have a higher 30-day mortality compared to non-DOAC users |
Franklin et al. 2018 [37] | NR | NR | One DOAC and three controls received spinal anaesthesia as an adjunct to general endotracheal anaesthesia. One control received spinal anaesthesia with MAC sedation. Otherwise all had general endotracheal anaesthesia without adjuncts | Mean (SD) estimated time between most recent ingestion and surgery = 39.5 (14.7) hours | NR | Peri-operative outcomes: (1) estimated blood loss (EBL) (mL) (2) transfusion rate (3) TTS (h) Post-operative outcomes: (4) LOS (5) Peri-operative complications, including haematoma formation, persistent serous drainage, thromboembolic events, or need for re-operation (6) Readmission rate (7) in-patient, 30-day, 90-day, and 1-year survival | Peri-operative outcomes: (1 and 2) no difference for EBL, transfusion rates, or blood volume transfused (3) DOACs (28.9 h) within 48 h of admission had longer TTS than controls (21.4 h) Post-operative outcomes: (4, 5) No difference in LOS or peri-operative complication rates (6) DOACs (21%) readmitted at higher rate vs. controls (5.3%) (8) No difference in survival at in-patient, 30 days, 90 days, or at 1 year. Survival at 1 year was DOAC (70.6%) vs. controls (59.1%) |
Frenkel Rutenberg et al. 2018 [51] | Need for blood transfusion during hospitalisation | Time from admission to surgery | NR | NR | NR | Primary: (1) in-hospital and 1-year mortality Secondary: (1) TTS within 48 h; (2) complication (e.g. infection, cardiovascular, pulmonary, renal, neurological, thromboembolic); (3) blood transfusions; (4) readmission within 1 year | Primary: (1) No difference for in-hospital or 1-year mortality Secondary: (1) Lower proportion of DOAC (51%) and VKAs (59%) had TTS within 48 h vs. no-anticoagulation (92%) (2) No difference in-hospital complications (3) No difference in blood transfusions (4) No difference in readmissions |
Gosch et al. 2020 [52] | Major bleeding defined as decrease in haemoglobin level of 2 g per decilitre or more over a 24 h period, transfusion of ≥ 2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome or retroperitoneal) or fatal bleeding | NR | NR | NR | NR | Primary: (1) in-hospital mortality; (2) TTS; (3) LOS; (4) ICU and ICU LOS; (5) place of discharge; (6) mobility; (7) complications (incl revision surgery, wound infections, urinary tract infection, pneumonia, myocardial infarction, stroke, thromboembolic events, falls during hospital stay, minor and major bleeding, delirium); (8) blood loss; (9) need for packed red cells, thrombocytes, prothrombin complex concentrate, fresh frozen plasma | Primary: (1) no difference in in-hospital mortality for DOAC (3.8%) vs. VKA (20%) or no anticoagulants (9.8%) (2) TTS longer for DOAC (42.7 h) vs. no anticoagulants (30 h), but no difference to VKA (40.5 h); (3) LOS longer for DOAC (17.2 days) vs. no anticoagulants (12.6 days) but no difference to VKA (14.4 days); (4) no difference in ICU and ICU LOS between DOACs vs. VKA or no anticoagulants; (5) no difference in discharge location; (6) No difference in mobility at discharge; (7) no difference in any complications, except for minor bleeding, which was higher for VKA (33.3%) vs. no anticoagulants (6.6%), but no difference to DOAC (19.2%); (8) no difference in decrease of haemoglobin; (9) no difference in need for packed red cells |
Hourston et al. 2020 [42] | NR | Time from admission to theatre | NR | NR | None used | Primary: (1) TTS; (2) LOS; (3) 30-day; 6- and 12-month mortality | Primary: (1) TTS longer for DOAC (29 h) vs. warfarin (27 h) and no anticoagulants (22 h). DOAC not associated with increase in TTS > 48 h Subgroup analysis found apixaban and dabigatran associated with delay > 36 h, but not rivaroxaban. None were associated with a delay > 48 h (2) No difference for LOS (3) Warfarin (22%) lower 30-day survival, but not DOACs (6%) or no anticoagulation (4%). No difference for 6- or 12-month mortality |
King et al. 2020 [38] | Measured as greatest haemoglobin value minus lowest haemoglobin value from admission to post-operative day 2 | Time from hospital admission to surgery | NR | NR | NR | Primary: (1) Blood transfusion rates; (2) peri-operative blood loss; (3) acute and total LOS; (4) TTS; (5) 30- and 90-day mortality; (6) re-operation; (7) haematoma rates | Primary: (1) no difference in blood transfusion rates (2) No difference in peri-operative blood loss (3) No difference in acute or total LOS (4) TTS longer for early DOAC (32.2 h) than no DOAC (26.0 h) (5) No difference in 30-day mortality. However, late DOAC (36.4%) had higher 90-day mortality vs. early DOAC (0%) (6) No difference in re-operation (7) Nil haematomas |
Leer Salvesen et al. 2020 [43] | Intra-operative blood loss estimated by the surgical team Blood transfusions for patients with Hb < 9 g/dL and collected from medical records | Time from admission to surgery | General anaesthesia (n = 22 DOACs; n = 10 no anticoagulants). Spinal anaesthesia (n = 25 DOACs; unspecified for anticoagulants) | NR | NR | Primary: (1) TTS; (2) LOS Secondary: (1) in-hospital, 30-day and 6-month mortality; (2) readmission within 30 days and 6 months; (3) Blood loss during surgery; (4) blood transfusions; (5) wound ooze | Primary: (1) No difference TTS DOAC (28.9 h) vs. no anticoagulants (26.1 h) (2) No difference in LOS DOAC (6.6 days) vs. no anticoagulants (6.1 days) Secondary: (1) No difference in in-hospital (4.3% vs. 3.4%), 30-day (10.6% vs. 12.7%) or 6-month (23.4% vs. 22.1%) mortality for DOAC vs. no anticoagulants, respectively (2) No difference in 30-day or 6-month readmission (3) No difference in mean blood loss during surgery (4) No difference in transfusion rates (5) Wound ooze higher for DOACs (26%) vs. no anticoagulant (5.6%) |
Lott et al. 2019 [12] | Surgical blood loss | Early: surgery within 48 h of presentation; or delayed: surgery > 48 h of presentation | General anaesthesia; spinal anaesthesia, unspecified by DOAC or PAI group | NR | NR | Primary: (1) length of surgery; (2) blood loss during surgery (mL); (3) transfusion requirement; (4) complications (i.e., sepsis, pneumonia, DVT/PE, acute myocardial infarction, acute kidney injury, stroke, surgical site haematoma, decubitus ulcer, urinary tract infection, acute respiratory failure, acute anaemia, cardiac arrest, and inpatient mortality); (5) transfer to ICU/ step-down unit | Primary: (1) no difference for surgery length for DOACs or PAIs; (2) no difference for blood loss for DOACs or PAIs; (3) no difference for transfusions for DOACs or PAIs; (4) no difference for DOACs or PAIs for complications for those treated within 48 h or > 48 h of admission; (5) no difference for ICU transfers for patients treated within 48 h or > 48 h (unspecified ICU transfers by DOACs or PAIs) |
Mahmood et al. 2021 [40] | Hb levels on admission and the first post-operative day to calculate post-operative Hb drop | Early (i.e., within 24 h of admission) or late (> 24 h of admission) | NR | Aspirin, clopidogrel, DOACs were stopped on admission and surgery was advocated within 36 h, unless patient needed further optimisation or medical workup | Warfarin stopped on admission and 10 mg of intravenous vitamin K given; and INR checked at 6 h. If level > 1.5 further intravenous vitamin K given | Primary: (1) TTS; (2) mortality at 30-days and 1 year; (3) post-operative Hb drop; (4) transfusion rate; (5) wound ooze; (6) infection rate (i.e., prescribed antibiotics); (7) re-operation rate | Primary: (1) no difference in mean TTS (hrs): control (23.5); PAI (24.4); warfarin (29.6); DOAC (28.1) (2) Difference in 30-day mortality: control (4.8%); PAI (12.6%); Warfarin (7.0%); DOAC (9.5%) and 1-year mortality: control (22.4%); PAI (32.3%); warfarin (29.3%); DOAC (29.0%) (3) No difference in post-operative Hb. However sub-group analysis showed difference for DOAC group for TTS < 24 h (20.1 g/L) vs. TTS > 24 h (14.7 g/L) (4) Difference in transfusion rate: control (21.6%); PAI (32.3%); Warfarin (21.7%); DOAC (23.2%) (5) Difference in wound ooze: control (22.2%); PAI (26.9%); warfarin (40.2%); DOAC (24.6%). Sub-group analysis showed difference for PAI group for TTS < 24 h (30.4%) vs. TTS > 24 h (18.4%) and Warfarin group for TTS < 24 h (27.5%) vs. TTS > 24 h (50.0%) (6) No difference in infection rates: control (1.0%); PAI (0.8%); warfarin (0%); DOAC (2.9%) (7) No difference in re-operation rates: control (0.6%); PAI (0.8%); warfarin (0%); DOAC (2.9%) |
Mullins et al. 2018 [26] | Peri-operative blood loss and blood transfusions | NR | NR | NR | NR | Primary: (1) TTS; (2) peri-operative change in in Hb concentration; (3) blood transfusion; (4) re-operation; (5) 30-day mortality | Primary: (1) no difference in TTS: DOACs (19 h) v no-DOACs (19 h); (2) no difference in peri-operative change in Hb concentration: DOACs (23 g/L) vs. no-DOACs (23 g/L); (3) no difference in blood transfusion: DOACs (18%) vs. no-DOACs (10%); (4) no difference in re-operation: DOACs (5%) vs. no-DOACs (n = 0%) (5) No difference in 30-day mortality: DOACs (2%) vs. no-DOACs (8%) |
Rostagno et al. 2021 [41] | Need for blood transfusion | NR | NR | NR | High-risk elective surgery was allowed 48 h after last administration for apixaban, edoxaban and rivaroxaban. Dabigatran timing was related to renal function (creatinine clearance) | Primary: (1) TTS; (2) % treated within 48 h; (3) LOS; (4) % with blood transfusion; (5) in-hospital mortality; (6) intra-operative complication (type not specified); (7) post-operative complications (anaemia, respiratory failure, acute renal failure, pneumonia, sepsis, wound infection, PE, DVT, acute myocardial infarction, acute heart failure, delirium, stroke) | Primary: (1) TTS longer for DOACs (3.6 h) vs. no anticoagulants (2.2 h) (2) Less DOACs (47%) surgery < 48 h vs. no anticoagulants (80%) (3) No difference in LOS: DOAC (14 days) vs. no anticoagulants (14.6 days) (4) No difference for blood transfusion: DOAC (46%) vs. no anticoagulants (41%) (5) No difference in mortality: DOACs (1.5%) vs. no anticoagulants (3.4%) (6) No difference in intra-operative complications (7) No difference in post-operative complications, except for anaemia (Hb < 8.0 g/dl): DOACs (37%) vs. no anticoagulants (12%) |
Saliba et al. 2020 [44] | Intra-operative bleeding subjectively estimated by the surgeon | NR | Of the 1108 patients with TTS, 69.9% received general anaesthesia and 30.1% received regional anaesthesia | NR | NR | Primary: (1) all-cause in-hospital mortality and mortality at 30-day, 90-day and 1-year Secondary: (1) LOS; (2) TTS within 48 h; (3) blood transfusion; (4) intra-operative bleeding | Primary: (1) compared to no anticoagulant use, DOACs had lower odds of mortality at 30 and 90 days and at 1 year Secondary: (1) Compared to no anticoagulant use, DOACs and VKAs users had longer LOS (2) Compared to no anticoagulant use, DOAC and VKA users had lower odds of surgery within 48 h (3) Compared to no anticoagulant use, no difference in proportion of DOAC or VKA users who received a blood transfusion (4) Compared to no anticoagulant use, no difference in intra-operative moderate-severe bleeding for DOAC or VKA users |
Scherman et al. 2019 [45] | Peri-operative haemoglobin change as the difference between pre- and post-operative Hb levels divided by pre-operative Hb level multiplied by 100 Blood transfusions within 1 week from surgery | Time from admission to surgery | NR | NR | If patient had normal kidney function, patient taking rivaroxaban and apixaban were operated on after 24-36 h. Patients taking dabigatran were operated on 12-24 h after last tablet | Primary: (1) %Hb change; (2) blood transfusions; (3) 30-day and 1-year mortality Secondary: (1) TTS; (2) % of HF surgery within 48 h | Primary: (1) No difference in %Hb change between DOACs and no-anticoagulants: CRIF DOACs (22.6%) and no-anticoagulants (24.0%) and HA DOACs (21.7%) and no anticoagulants (21.0%) (2) No difference for CRIF or HA for blood transfusion rates for DOACs (8.3% & 10.3%, respectively) and no anticoagulants (7.9% & 7.4%, respectively) (3) No difference for CRIF or HA for blood 30-day mortality for DOACs (6.7% & 6.9%, respectively) and no anticoagulants (4.4% & 6.1%, respectively) 1-year mortality was higher for CRIF for DOACs (26.7%) compared to no-anticoagulants (16.1%), but not for HA for DOACs (13.8%) compared to no anticoagulants (21.1%) Secondary: (1) TTS longer for CRIF for DOACs (40.2 h ± 26.9) compared to no anticoagulants (31.2 h ± 22.2) and no difference for HA (DOACs 42.3 h ± 27.3 and no-anticoagulants 36.6 h ± 25.8) (2) No difference in % of HF surgery within 48 h between DOACs and no anticoagulants: CRIF DOACs (74%) and no anticoagulants (82%) and HA DOACs (74%) and no anticoagulants (78%) |
Schuetze et al. 2019 [46] | Decision for blood transfusion based on Hb < 8 g/dl with accompanying hypertension, tachycardia or dizziness | NR | NR | NR | NR | Primary: (1) rate of transfusion; (2) pre- to 24 h post-operative Hb difference; (3) post-operative haematoma requiring revision surgery Secondary: (1) 1-year mortality; (2) post-operative complications (i.e., DVT, cardiac infarction, stroke, pneumonia, urinary tract infection, acute renal failure, deep tissue infection; (3) mean TTS | Primary: (1) Increased need for blood transfusion for DOACs (38.5%) compared to no anticoagulation (16.4%), ASS (21.6%), PAI (26.7%) or VKA (24.0%) (2) No difference for ASS, PAI, DOAC, no anticoagulation for Hb-difference. Patients on VKA had lower post-operative Hb difference (3) No difference for PAI, DOAC, ASS, VKA, no anticoagulation for post-operative haematoma Secondary: (1) No difference for PAI, DOAC, ASS, VKA, no anticoagulation for 1-year mortality (2) No post-operative complications identified (3) No difference for PAI (8.5 h), DOAC (9.5 h), ASS (7.4 h), VKA (10.0 h), no anticoagulation (8.2 h) for TTS |
Shani et al. 2021 [53] | NR | Time from arrival in hospital emergency room until surgery | NR | NR | NR | Primary: (1) TTS < 48 h Secondary: (1) TTS; (2) LOS; (3) unadjusted and adjusted 30-day and 6-month mortality | Primary: (1) Lower proportion of DOACs (69.7%) had TTS < 48 h (warfarin: 69.8%) compared to patients not on anticoagulants (89.3%) Secondary: (1) Unadjusted TTS longer for DOACs (1.9 ± 1.6 days) and warfarin (2.0 ± 2.2 days) compared to no anticoagulants (1.3 ± 1.8 days). TSS remained longer for DOACs after adjusting for age, gender and Charlson score (2) LOS longer for DOACs (9.9 ± 9.0 days) and warfarin (9.5 ± 9.3 days) compared to no anticoagulants (8.8 ± 8.6 days) (3) Unadjusted 30-day mortality higher for DOACs (6.0%) and warfarin (10.0%) compared to no anticoagulants (4.2%). Unadjusted 6-month mortality higher for DOACs (16.9%) and warfarin (25.1%) compared to no anticoagulants (13.1%) After adjusting for age, gender and Charlson score, 30-day and 6-month mortality were similar for DOACs vs. no anticoagulants and higher for warfarin compared to DOACs or no anticoagulants |
Tarrant et al. 2020 [39] | Peri-operative Hb and admission estimate glomerular filtration rate (eGFR) | TTS from admission and TTS after last DOAC dose (Ts) | General (n = 96 DOACs and n = 55 controls) Neuraxial (n = 15 DOACs and n = 56 controls) | NR | NR | Primary: (1) 30-day mortality Secondary: (1) Number of packed cells transfused; (2) Post-operative day (POD) 1 Hb; (3) Serious adverse events (SAE) including myocardial infarction, acute renal failure, respiratory failure, cerebrovascular accident, DVT, PE, pneumonia, bacteraemia/sepsis, surgical site infection, post-operative haemorrhage; (4) TTS from admission; (5) Median LOS (Q1-Q3); (6) inpatient mortality | Primary: (1) No difference in 30-day mortality between DOACs (14%) and controls (6.3%) Secondary: (1) Transfusion not reported by DOACs vs. controls (2) POD1 Hb not reported by DOACs vs. controls (3) SAEs not reported by DOACs vs. controls (4) DOACs higher TTS (1.8 ± 1.3 days) vs. controls (1.2 ± 0.7 days) (5) Longer LOS for DOACs [11 (6.5–18) days] vs. controls [6.9 (4.2–11) days] (6) Higher inpatient mortality for DOAC (7.1%) vs. controls (0.9%) |
Tran et al. 2015 [54] | Estimated intra-operative blood loss from anaesthesia record. Blood transfusions Bleeding events as defined by ISTH criteria | Time from admission to surgery | NR | NR | NR | Primary: (1) TTS Secondary: (1) Intra-operative blood loss; (2) blood transfusion; (3) bleeding events; (4) DVT or PE; (5) stroke; (6) in-hospital mortality | Primary: (1) Median TTS longer for DOAC and VKA vs. controls (40 h vs. 26.2 h). Longer TTS for DOAC vs. VKA (66.9 h vs. 39 h) Secondary: (1, 2, 3) No difference in major bleeding episodes for DOAC and VKA vs. controls (4) No difference in DVT or PE for DOAC and VKA vs. controls (5) No difference in stroke for DOAC and VKA vs. controls (6) No difference in in-hospital mortality for DOAC and VKA vs. controls |
Viktil et al. 2019 [55] | Difference between last Hb measurement before surgery and the first after surgery | Time from admission to surgery | NR | NR | NR | Primary: (1) serum concentrations; (2) elimination half-life Secondary: (1) TTS; (2) difference in Hb | Primary: (1) 50% of DOAC users had serum concentrations above reference ranges at admission (2) DOACs prolonged elimination half-life (possibly due to reduced renal function and low drug clearance) Secondary: (1) TTS longer for DOAC vs. Warfarin vs. PAI (median 44 vs. 25 vs. 22 h) (2) Hb lower for Warfarin vs. DOACs vs. PAIs. (median 1.1 vs. 2.2 vs. 1.9) |
Time to surgery
Blood loss and transfusions
Post-operative complications and hospital LOS
Mortality
Quality assessment
Authors and publication year | Q1 | Q2 | Q3 | Q4 | Q5a | Q5b | Q6a | Q6b | Q8 | Q9 | Q10 | Q11 | Q12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bruckbauer et al. 2019 [48] | Y | Y | Y | Y | C | C | NA | NA | Y | Y | Y | Y | Y |
Cafaro et al. 2019 [49] | Y | Y | Y | Y | C | C | NA | NA | Y | Y | Y | Y | Y |
Creeper et al. 2020 [50] | Y | Y | Y | Y | C | N | Y | Y | Y | Y | Y | Y | Y |
Daugaard et al. 2019 [47] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Frenkel Rutenberg et al. 2018 [51] | Y | Y | Y | Y | C | C | Y | Y | Y | Y | Y | Y | Y |
Hourston et al. 2020 [42] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
King et al. 2020 [38] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Leer-Salvesen et al. 2020 [43] | Y | Y | Y | Y | N | N | Y | Y | Y | Y | Y | Y | Y |
Lott et al. 2019 [12] | Y | Y | Y | Y | N | N | NA | NA | Y | Y | Y | Y | Y |
Mahmood et al. 2021 [40] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Saliba et al. 2020 [44] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Scherman et al. 2019 [45] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Schuetze et a. 2019 [46] | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y |
Shani et al. 2021 [53] | Y | Y | Y | Y | C | C | Y | Y | Y | Y | Y | Y | Y |
Viktil et al. 2019 [55] | Y | Y | Y | Y | C | C | NA | NA | N | C | Y | Y | Y |
1. Did the study address a clearly focussed issue? | 6b. Was the follow-up of subjects long enough? |
2. Was the cohort recruited in an acceptable way? | 7. What are the results of this study? |
3. Was the exposure accurately measured to minimise bias? | 8. How precise are the results? |
4. Was the outcome accurately measured to minimise bias? | 9. Do you believe the results? |
5a. Have the authors identified all important confounding factors? | 10. Can the results be applied to the local population? |
5b. Have they taken into account the confounding factors in the design and/or analysis? | 11. Do the results of this study fit with other available evidence? |
6a. Was the follow-up of the subjects complete enough? | 12. Does the study have implications for practice? |
Authors and publication year | Q1 | Q2 | Q3 | Q4 | Q5 | Q6a | Q6b | Q7 | Q8 | Q9 | Q10 | Q11 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Franklin et al. 2018 [37] | Y | Y | Y | C | Y | Y | Y | C | Y | Y | Y | Y |
Gosch et al. 2020 [52] | Y | Y | Y | C | Y | Y | C | C | C | Y | Y | Y |
Mullins et al. 2018 [26] | Y | Y | Y | C | Y | Y | Y | C | Y | Y | Y | Y |
Rostagno et al. 2021 [41] | Y | Y | Y | Y | Y | Y | C | C | C | Y | Y | Y |
Tarrant et al. 2020 [39] | Y | Y | Y | Y | Y | Y | Y | C | Y | Y | Y | Y |
Tran et al. 2015 [54] | Y | Y | Y | Y | Y | Y | C | C | C | Y | Y | Y |
1. Did the study address a clearly focussed issue? | 6b. Have the authors taken account of the potential confounding factors in the design and/or in their analysis? |
2. Did the authors use an appropriate method to answer their question? | 7. How large was the treatment effect? |
3. Were the cases recruited in an acceptable way? | 8. How precise was the estimate of the treatment effect? |
4. Were the controls selected in an acceptable way? | 9. Do you believe the results? |
5. Was the exposure accurately measured to minimise bias? | 10. Can the results be applied to the local population? |
6a. Aside from the experimental intervention, were the groups treated equally? | 11. Do the results of this study fit with other available evidence? |