PERIPROCEDURAL ANTITHROMBOTIC RECOMMENDATIONS













  • ✝Top number is overall risk. Bottom number is risk among subgroup of patients who underwent high-bleeding-risk procedure.
  • Outcomes were measured for 30 days after the procedure
  • Reference [15]
Outcomes in Patients with A fib using Simple Anticoagulant Protocol
Drug Major bleeding✝ Arterial thromboembolism
Apixaban 1.35%
2.96%		 0.16%
Dabigatran 0.90%
0.88%		 0.60%
Rivaroxaban 1.85%
2.95%		 0.37%



Procedure Bleeding Risk Categories Used in Study
High risk procedures/surgery
  • Any surgery requiring neuraxial anesthesia
    • neuraxial anesthesia/injection
    • epidural anesthesia/injection
  • Major intracranial or neuraxial surgery
    • brain cancer resection
    • laminectomy or neuraxial tumour resection
    • intracranial (subdural, epidural) bleed evacuation
  • Major cardiac surgery
    • coronary artery bypass
    • valve replacement or repair
  • Major vascular surgery
    • aortic aneurysm repair
    • aortobifemoral bypass, popliteal bypass
    • carotid endarterectomy
  • Major orthopedic surgery
    • hip arthroplasty or hip fracture repair
    • knee arthroplasty or tibial osteotomy
    • shoulder arthroplasty
    • metatarsal osteotomy
  • Major thoracic surgery
    • lobectomy, pneumonectomy
    • esophagectomy
  • Major abdominopelvic surgery
    • hepatobiliary cancer resection
    • pancreatic cancer or pseudocyst resection
    • colorectal and gastric cancer resection
    • diverticular disease resection
    • inflammatory bowel disease resection
    • renal cancer resection
    • bladder cancer resection
    • endometrial cancer resection
    • ovarian cancer resection
    • radical prostatectomy
  • Other major cancer or reconstructive surgery
    • head and neck cancer surgery
    • reconstructive facial, abdominal, limb surgery
Low Bleeding Risk Surgery/Procedures
  • Gastrointestinal procedures
    • colonoscopy
    • gastroscopy
    • sigmoidoscopy
    • endoscopic retrograde pancreaticocholangiography
    • capsule endoscopy
    • push enteroscopy
    • Barrett’s esophagus ablation
  • Cardiac procedures
    • permanent pacemaker implantation or battery change
    • internal cardiac defibrillator implantation or battery change
    • arterioventricular node ablation
    • coronary artery angiography (radial approach)
  • Dental procedures
    • tooth extraction (up to two extractions)
    • endodontic (root canal) procedure
  • Skin procedures
    • skin biopsy
  • Eye procedures
    • phacoemulsification (cataract)



  • Reference [1]
ACCP 2012 Periprocedural Aspirin Recommendations
Minor dental procedures, minor dermatological procedures, and cataract surgery
  • Continue aspirin
Noncardiac surgery
  • Patients at moderate to high risk for cardiovascular events
    • Continue aspirin
    • NOTE: A large, randomized controlled trial published in 2014 found that aspirin had no benefit in high-risk patients undergoing noncardiac surgery. See POISE-2 study for more.
      • Moderate to high risk defined as one or more of the following:
        • Patients with ischemic heart disease
        • Compensated or prior congestive heart failure
        • Diabetes mellitus
        • Kidney disease
        • Cerebrovascular disease
      • Other considerations:
        • If the surgery is associated with an increased risk for perioperative cardiovascular events, such as carotid endarterectomy and peripheral artery bypass surgery, then continuing aspirin may be beneficial
        • For surgeries that are associated with an increased risk of bleeding (ex. prostate and intracranial surgery), then the risk/benefit ratio of continuing aspirin should be considered

  • Patients at low risk for cardiovascular events
    • Stop aspirin 7 - 10 days before surgery
Coronary artery bypass graft surgery (CABG)
  • Continue aspirin
  • NOTE: A large, randomized controlled trial published in 2016 found that preoperative aspirin had no benefit in high-risk patients who were undergoing CABG. See ATACAS trial for more.

ACCP 2012 Periprocedural Warfarin Recommendations
Minor dental procedures
  • Two options
    • 1. Continue warfarin and administer oral prohemostatic agent (ex. tranexamic acid)
    • 2. Stop warfarin 2-3 days before the procedure (if INR is between 2 - 3, it should drop to 1.6 - 1.9 at time of procedure)
Minor dermatological procedures and cataract surgery
  • Continue warfarin and optimize local hemostasis
Other surgeries
  • Patients at high risk for thromboembolism (see risk categories below)
    • Stop warfarin 5 days before surgery
    • Administer bridging therapy (typically with SQ Low Molecular Weight Heparin (LMWH), ex. Lovenox®)
    • Restart warfarin 12 - 24 hours after surgery and when there is adequate hemostasis

  • Patients at moderate risk for thromboembolism (see risk categories below)
    • The decision to administer bridging therapy should be made on an individual basis

  • Patients at low risk for thromboembolism (see risk categories below)
    • Stop warfarin 5 days before surgery
    • Do not administer bridging anticoagulation therapy
    • Restart warfarin 12 - 24 hours after surgery and when there is adequate hemostasis [1]

ACCP 2012 Thromboembolism Risk Categories
Atrial fibrillation
  • High risk
    • CHADS2 score of 5 or 6
    • Recent (within 3 months) stroke or TIA
    • Rheumatic valvular heart disease
  • Moderate risk
    • CHADS2 score of 3 or 4
  • Low risk
    • CHADS2 score of 0 - 2, assuming no prior stroke or TIA
    • NOTE: A recent study found no benefit of bridging therapy in patients with an average CHADS2 score of 2.3 (see BRIDGE study for more)
  • Other considerations (these factors may affect decision for bridging therapy)
    • High risk surgeries - certain surgeries carry a higher risk for stroke and thromboembolism (ex. heart valve replacement, carotid endarterectomy, and major vascular surgery)
    • Prior thromboembolism during warfarin interruption
    • Any history of stroke or TIA [1]
Venous thromboembolism
  • High risk
    • Recent (within 3 months) DVT or PE
    • Severe hypercoagulable disorder (Protein C and S deficiency, antithrombin deficiency, antiphospholipid antibodies, multiple abnormalities)
  • Moderate risk
    • DVT or PE within past 3 - 12 months
    • Non-severe hypercoagulable disorder (heterozygous Factor V Leiden or prothrombin gene mutation)
    • Recurrent DVT or PE
    • Active cancer (treated within 6 months or palliative)
  • Low risk
    • DVT or PE greater than 12 months ago and no other risk factors
  • Other considerations (these factors may affect decision for bridging therapy)
    • High risk surgeries - certain surgeries carry a higher risk for stroke and thromboembolism (ex. heart valve replacement, carotid endarterectomy, and major vascular surgery)
    • Prior thromboembolism during warfarin interruption
    • Any history of stroke or TIA [1]
Mechanical heart valve
  • High risk
    • Any mitral valve prosthesis
    • Any caged-ball or tilting disc aortic valve prosthesis
    • Recent (within 6 months) stroke or TIA
  • Moderate risk
    • Bileaflet aortic valve prosthesis and one or more of the following risk factors:
      • Atrial fibrillation
      • Prior stroke or TIA
      • Hypertension
      • Diabetes
      • Congestive heart failure
      • Age > 75 years
  • Low risk
    • Bileaflet aortic valve prosthesis without atrial fibrillation and no other risk factors for stroke
  • Other considerations (these factors may affect decision for bridging therapy)
    • High risk surgeries - certain surgeries carry a higher risk for stroke and thromboembolism (ex. heart valve replacement, carotid endarterectomy, and major vascular surgery)
    • Prior thromboembolism during warfarin interruption
    • Any history of stroke or TIA [1]


AHA 2016 Periprocedural Recommendations for DAPT
Elective, noncardiac surgery
  • Drug-eluting stents (DES)
    • < 3 months since DES implantation
      • Delay surgery
    • 3 - 6 months since DES implantation
      • Proceeding with surgery may be considered
      • If having surgery, discontinue DAPT before surgery (aspirin should be continued if possible)
      • After surgery, restart DAPT as soon as possible if still indicated
      • There is no convincing evidence that "bridging therapy" with parenteral antiplatelet/anticoagulant agents is beneficial
    • ≥ 6 months since DES implantation
      • Proceed with surgery
      • Discontinue DAPT before surgery (aspirin should be continued if possible)
      • After surgery, restart DAPT as soon as possible if still indicated
      • There is no convincing evidence that "bridging therapy" with parenteral antiplatelet/anticoagulant agents is beneficial [11]

  • Bare metal stents (BMS)
    • < 30 days since BMS implantation
      • Delay surgery
    • ≥ 30 days since BMS implantation
      • Proceed with surgery
      • If having surgery, discontinue DAPT before surgery (aspirin should be continued if possible)
      • After surgery, restart DAPT as soon as possible if still indicated
      • There is no convincing evidence that "bridging therapy" with parenteral antiplatelet/anticoagulant agents is beneficial [11]
Coronary artery bypass graft surgery (CABG)
  • Urgent on-pump CABG
    • Aspirin - do not stop aspirin before surgery
    • P2Y12 inhibitor:
      • Clopidogrel - stop clopidogrel 24 hours before surgery if possible
      • Ticagrelor - stop ticagrelor 24 hours before surgery if possible [7]

  • Elective CABG
    • Aspirin
      • Do not stop aspirin before surgery
    • P2Y12 inhibitor:
      • Clopidogrel - stop clopidogrel 5 days before surgery
      • Ticagrelor - stop ticagrelor 5 days before surgery
      • Prasugrel - stop prasugrel 7 days before surgery [3]

AHA 2017 Periprocedural Recommendations for Mechanical Heart Valves
Minor procedures (such as dental extractions or cataract removal) where bleeding is easily controlled
  • Continue warfarin [6]
Other invasive or surgical procedures
  • Patients with bileaflet mechanical aortic valve replacement (AVR) and no other risk factors for thrombosis
    • Temporary interruption of warfarin without bridging agents while the INR is subtherapeutic - warfarin is stopped 2 to 4 days before the procedure (so the INR falls to < 1.5 for major surgical procedures) and restarted as soon as bleeding risk allows, typically 12 to 24 hours after surgery [6]
  • Patients with any of the following:
    • Mechanical AVR and any thromboembolic risk factor
    • Older-generation mechanical AVR
    • Mechanical mitral valve replacement
      • Bridging therapy is reasonable. Risks of bleeding should be weighed against the benefits of thromboembolism prevention.




  • ✝Ticagrelor should be held for 3 - 5 days, and all other P2Y12 inhibitors should be held for 5 - 7 days
  • Reference [4]
ASGE 2016 Antiplatelet Recommendations for Elective GI Endoscopy
TE risk Procedure bleed risk Recommendation
Low Low
  • Continue ASA/NSAIDs
  • Continue P2Y12 inhibitor
Low High
  • Continue ASA/NSAIDs
  • Discontinue P2Y12 inhibitors at least 5 days before endoscopy or switch to ASA✝
  • For patients taking dual antiplatelet therapy, hold P2Y12 inhibitors for at least 5 days and continue ASA✝
High Low
  • Continue ASA/NSAIDs
  • Continue P2Y12 inhibitors
High High
  • Continue ASA/NSAIDs
  • Discontinue P2Y12 inhibitors at least 5 days before endoscopy or switch to ASA✝
  • For patients taking dual antiplatelet therapy, hold P2Y12 inhibitors for at least 5 days and continue ASA✝

  • Reference [4]
ASGE 2016 Anticoagulant Recommendations for Elective GI Endoscopy
TE risk Procedure bleed risk Recommendation
Low Low
  • Continue anticoagulation
Low High
  • Discontinue anticoagulation
  • Restart warfarin on same day as procedure
  • Restart Factor Xa inhibitors and direct thrombin inhibitors once adequate hemostasis is achieved
High Low
  • Continue anticoagulation
High High
  • Discontinue anticoagulation
  • Bridging therapy
  • Restart warfarin on same day as procedure
  • Restart Factor Xa inhibitors and direct thrombin inhibitors once adequate hemostasis is achieved

  • Reference [4]
ASGE Thromboembolism Risk Categories
Nonvalvular atrial fibrillation
Venous thromboembolism (VTE)
  • High risk
    • Recent (within 3 months) VTE
    • Severe thrombophilia (deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; multiple abnormalities)
  • Medium risk
    • VTE within the past 3 - 12 months
    • Nonsevere thrombophilia (heterozygous factor V Leiden or prothrombin gene mutation)
    • Recurrent VTE
    • Active cancer (treated within 6 months or palliative)
  • Low risk
    • VTE > 12 months previous and no other risk factors
Mechanical heart valve
  • High risk
    • Any mitral valve prosthesis
    • Any caged-ball or tilting disc aortic valve prosthesis
    • Recent (within 6 months) CVA or TIA
  • Medium risk
    • Bileaflet aortic valve prosthesis and one or more of the following risk factors: A fib, prior CVA or TIA, hypertension, diabetes, congestive heart failure, age ≥ 75 years
  • Low risk
    • Bileaflet aortic valve prosthesis without A fib and no other risk factors for CVA
Recent cardiac stent (antiplatelet therapy)
  • High risk
    • Placement of drug-eluting stent ≤ 12 months
    • Placement of bare metal stent ≤ 1 month
    • Placement of bare metal stent after acute coronary syndrome ≤ 12 months
  • Other conditions that can raise cardiovascular risk include:
    • Prior history of stent occlusion
    • History of acute coronary syndrome or ST-elevation MI
    • Multivessel PCI
    • Diabetes
    • Kidney failure



  • Reference [12]
SEC 2018 Recommendations for Antiplatelet Therapy
TE risk Procedure bleed risk Recommendation
Low Low / Moderate
  • Continue ASA
  • Stop P2Y12 inhibitor✝ and replace with ASA if possible
Low High
  • Continue ASA except when contraindicated (e.g. neurosurgery)*
  • Stop P2Y12 inhibitor✝ and replace with ASA if possible
Moderate / High Low
  • Continue ASA
  • Continue P2Y12 inhibitors
Moderate / High Moderate
  • Individualize therapy based on patient risk factors
  • Continue ASA
  • Assess withdrawal of P2Y12 inhibitor
Moderate / High High
  • Individualize therapy based on patient risk factors
  • Continue ASA unless contraindicated*
  • Stop P2Y12 inhibitor✝ and replace with ASA if possible
  • Assess bridging therapy
  • ✝Stop clopidogrel 5 days before surgery; Stop ticagrelor 3 - 5 days before surgery; Stop prasugrel 7 days before surgery
  • *If necessary, withdraw ASA 3 days before surgery
  • Restart antiplatelet therapy within 24 hours of surgery if bleeding risk is low or moderate. Restart 48 - 72 hours when bleeding risk is high
  • NOTE: A large, randomized controlled trial published in 2014 found that aspirin had no benefit in high-risk patients undergoing noncardiac surgery. (see POISE-2 study). Also, a large, randomized controlled trial published in 2016 found that preoperative aspirin had no benefit in high-risk patients who were undergoing CABG (see ATACAS trial for more).

  • Reference [12]
SEC 2018 Recommendations for Anticoagulant Therapy
TE risk Procedure bleed risk Recommendation
Low / Moderate / High Low✝
  • Continue anticoagulation
Low / Moderate Low / Moderate / High
  • Discontinue anticoagulation
  • Do not use bridging therapy
High Low / Moderate / High
  • ✝Guidelines do not state specifically which procedures are okay to continue anticoagulation. Other guidelines state minor procedures such as dental extractions, minor derm procedures, and cataract surgery are okay for continued anticoagulation.
  • For procedures with a low or moderate bleeding risk, restart anticoagulation 24 hours after surgery and consider bridging therapy in patients taking warfarin with high thromboembolic risk
  • For procedures with a high bleeding risk, restart anticoagulation 48 - 72 hours after surgery without bridge therapy

  • Reference [12]
SEC Thromboembolism Risk Categories for Antiplatelet Therapy
Heart disease
Cerebrovascular disease
  • High risk
    • Ischemic stroke within 3 months
    • Carotid stent placement within 3 months
  • Moderate risk
    • Ischemic stroke within 3 - 6 months
    • Carotid stent placement within 3 - 6 months
  • Low risk
    • Ischemic stroke > 6 months ago
    • Carotid stent placement > 6 months ago
Peripheral vascular disease
  • High risk
    • Within 3 months of acute peripheral vascular event + revascularization with DES or stents used in chronic occlusions
  • Moderate risk
    • Within 3 - 6 months of acute peripheral vascular event + revascularization with DES or stents used in chronic occlusions
  • Low risk
    • > 6 months since acute peripheral vascular event + revascularization with DES or stents used in chronic occlusions

  • Reference [12]
SEC Thromboembolism Risk Categories for Anticoagulant Therapy
Atrial fibrillation
  • High risk
  • Moderate risk
  • Low risk
    • CHA2DS2-VASc score of 1 - 4
    • No history of stroke/TIA
    • NOTE: A recent study found no benefit of bridging therapy in patients with an average CHADS2 score of 2.3 (see BRIDGE study for more)
Venous thromboembolism (VTE)
  • High risk
    • Recent (within 3 months) VTE
    • Severe thrombophilia (homozygous factor V Leiden, prothrombin 20210A, protein C, protein S, or antithrombin deficiency, multiple defects, antiphospholipid syndrome)
  • Moderate risk
    • VTE within the past 3 - 12 months
    • Nonsevere thrombophilia (heterozygous factor V Leiden or prothrombin 20210A gene mutation)
    • Recurrent VTE
    • VTE + active cancer
  • Low risk
    • VTE > 12 months
Mechanical heart valve
  • High risk
    • Mitral valve
    • Tricuspid valve (including biological valve)
    • Aortic valve (monoleaflet)
    • Stroke/TIA in last 6 months
  • Moderate risk
    • Aortic valve + any of the following risk factors:
      • Atrial fib
      • Stroke/TIA > 6 months ago
      • Diabetes
      • Heart failure
      • Age > 75 years
  • Low risk
    • Aortic valve without other risk factors




When to hold P2Y12 inhibitors before procedures
Drug ASGE / SEC Manufacturer
Clopidogrel 5 days 5 days
Prasugrel 7 days 7 days
Ticagrelor 3 - 5 days 5 days
Ticlopidine N/A 10 - 14 days


  • Reference [12]
SEC recommendations on holding warfarin before procedures
INR 7 days before procedure Hold warfarin
> 3 7 days
2 - 3 6 days
< 2 5 days


  • Recommendations are for apixaban, rivaroxaban, and edoxaban only
  • Recommendations are from the ACC. Other recommendations may vary.
  • Anti-Xa level is a lab that measures the concentration of Factor Xa inhibitors in the blood
  • References [13,14]
Recommendations for holding Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) before procedures
CrCl (ml/min) Procedure bleeding risk Hold before procedure
≥ 30 Low ≥ 24 hours
15 - 29 Low ≥ 36 hours
< 15 Low No data. Consider anti-Xa level and/or ≥ 48 hours.
≥ 30 Moderate / High ≥ 48 hours
< 30 Moderate / High No data. Consider anti-Xa level and/or ≥ 72 hours.


  • dTT - dilute thrombin time assay (not widely available). A normal aPTT usually excludes clinically relevant levels if a sensitive reagent is used. A normal thrombin time (TT) excludes clinically relevant levels.
  • Recommendations are from the ACC. Other recommendations may vary.
  • References [13,14]
Recommendations for holding dabigatran before procedures
CrCl (ml/min) Procedure bleeding risk Hold before procedure
≥ 80 Low ≥ 24 hours
50 - 79 Low ≥ 36 hours
30 - 49 Low ≥ 48 hours
15 - 29 Low ≥ 72 hours
< 15 Low No data. Consider dTT and/or ≥ 96 hours.
≥ 80 Moderate / High ≥ 48 hours
50 - 79 Moderate / High ≥ 72 hours
30 - 49 Moderate / High ≥ 96 hours
15 - 29 Moderate / High ≥ 120 hours
< 15 Moderate / High No data. Consider dTT.


  • Drugs are typically cleared after 4 - 5 half-lives
  • ✝The manufacturer states that in trials, celecoxib had no effect on reduction of platelet aggregation or increase in bleeding time
  • *The manufacturer states that in trials, nabumetone had little effect on collagen-induced platelet aggregation and no effect on bleeding time
  • References [Manufacturer PI]
NSAID half-lives
Drug Half-life
Ibuprofen (Motrin®, Advil®) 2.2 hours
Naproxen (Aleve®, Anaprox®, etc.) 12 - 17 hours
Meloxicam (Mobic®) 15 - 20 hours
Celecoxib (Celebrex®)✝ 11 hours
Indomethacin (Indocin®) 4.5 hours
Ketorolac (Toradol®) 5 - 6 hours
Nabumetone (Relafen®)* 24 hours





  • Reference [1,10,14]
Bridging therapy recommendations
Pre-operative
  • Stop warfarin 5 days prior to scheduled surgery. When INR becomes subtherapeutic, start a bridging regimen.
  • If patient is receiving a Factor Xa inhibitor or dabigatran, start bridging regimen after omitting 2 - 3 doses of the drug
Bridging regimens
  • Enoxaparin (Lovenox®) 1 mg/kg twice a day OR 1.5 mg/kg once daily
  • Dalteparin (Fragmin®) 100 IU/kg twice a day OR 200 IU/kg once daily
  • IV unfractionated heparin to maintain aPTT 1.5 - 2 X the control aPTT
  • NOTE: When patient has a mechanical heart valve, twice daily LMWH regimens are recommended
Before procedure
  • LMWH
    • Twice daily regimen - withhold the last LMWH dose before surgery
    • Once daily regimens - give half the total daily dose the morning of the day before surgery
  • Unfractionated heparin (UFH)
    • Stop UFH 4 - 6 hours before surgery
Post-operative
  • Warfarin
    • Restart warfarin 12 - 24 hours after surgery when adequate hemostasis has been achieved
    • In patients who underwent surgery that has a high bleeding risk, resume LMWH or UFH (without bolus dose) 48 - 72 hours after surgery
    • In patients who underwent surgery that has a moderate or low bleeding risk, resume LMWH or UFH (without bolus dose) 24 hours after surgery
    • Continue bridging therapy until INR is therapeutic
    • NOTE: A study published in 2021 found that post-operative bridging therapy in patients receiving warfarin for A fib or mechanical heart valves was not beneficial [PMID 34108229]
  • Factor Xa inhibitors and dabigatran
    • Confirm that adequate hemostasis has been achieved
    • In patients who underwent surgery that has a high bleeding risk, resume medication 48 - 72 hours after surgery
    • In patients who underwent surgery that has a low bleeding risk, resume medication on the day following the procedure
    • Parenteral anticoagulation is generally not required

BRIDGE study - Periprocedural Bridging Therapy vs No Bridging Therapy in A Fib, NEJM (2015) [PubMed abstract]
  • The BRIDGE study enrolled 1884 patients taking warfarin for atrial fibrillation who were to undergo an elective operation or other elective invasive procedure that required interruption of warfarin therapy
Main inclusion criteria
  • Chronic (permanent or paroxysmal) atrial fibrillation or flutter
  • At least one CHADS2 criteria
Main exclusion criteria
  • Mechanical heart valve
  • Stroke, systemic embolism, or TIA within the previous 12 weeks
  • Major bleeding within previous 6 weeks
  • Planned cardiac, intracranial, or intraspinal surgery
Baseline characteristics
  • Average age 72 years
  • Average CHADS2 score - 2.3
  • CHADS2 score of 4 - 10%
  • CHADS2 score of 5 or 6 - 3%
  • Mitral valve heart disease - 16%
  • Concomitant antiplatelet therapy (aspirin or clopidogrel) - 37%
Randomized treatment groups
  • Group 1 (934 patients) - Bridging therapy
  • Group 2 (950 patients) - No bridging therapy
  • Bridging therapy - 1. warfarin stopped 5 days before procedure 2. dalteparin 100 U/kg twice a day starting 3 days before procedure and stopping 24 hours before procedure 3. warfarin restarted on the evening of or the day after the procedure 4. dalteparin resumed 12 to 24 hours after a minor (or low-bleeding-risk) procedure and 48 to 72 hours after a major (or high-bleeding-risk) procedure for 5 - 10 days (until INR was ≥ 2)
  • No bridging therapy - same as bridging therapy except placebo was given in place of dalteparin
Primary outcome: Arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding within 30 days after the procedure
Results

Duration: 30 days
Outcome Bridging therapy No bridging Comparisons
Arterial thromboembolism 0.3% 0.4% difference 0.1%, 95%CI [-0.6 to 0.8], p=0.73
Major bleeding 3.2% 1.3% RR 0.41, 95%CI [0.20 - 0.78], p=0.005

Findings: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding.



POISE-2 Study - Stopping vs Continuing Aspirin Before Noncardiac Surgery, NEJM (2014) [PubMed abstract]
  • The POISE-2 study enrolled 10,010 patients at increased risk for vascular complications who were scheduled to undergo noncardiac surgery
Main inclusion criteria
  • Undergoing major vascular surgery or a history of CAD, PVD, or stroke. Patients with ≥ 3 risk factors for CVD (e.g. DM, smoking, CHF, HTN, TIA, age ≥ 70 years, etc.) were also eligible.
Main exclusion criteria
  • Drug-eluting coronary stent < 1 year before surgery
  • Bare-metal coronary stent < 6 weeks before surgery
  • Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery
Baseline characteristics
  • Average age - 69 years
  • History of CAD - 23%
  • History of vascular disease - 33%
  • Undergoing major surgery - 78%
  • History of hypertension - 86%
  • Diabetes - 38%
Randomized treatment groups
  • Group 1 (4998 patients)
    • Patients not currently taking aspirin - Aspirin 200 mg just before surgery, then 100 mg a day for 30 days
    • Patients currently taking aspirin - Aspirin 200 mg just before surgery, then 100 mg for 7 days, then resume previous aspirin regimen
  • Group 2 (5012 patients)
    • Patients not currently taking aspirin - Placebo for 30 days
    • Patients currently taking aspirin - Placebo for 7 days, then resume previous aspirin regimen
  • For all patients who were taking aspirin at randomization, aspirin was required to be stopped at least 3 days before surgery. The median stop time was 7 days before surgery.
Primary outcome: The primary outcome was a composite of death or nonfatal heart attack 30 days after randomization
Results

Duration: 30 days
Outcome Aspirin Placebo Comparisons
Primary outcome 7% 7.1% HR 0.99, 95%CI [0.86 - 1.15], p=0.92
Overall mortality 1.3% 1.2% HR 1.05, 95%CI [0.74 - 1.49], p=0.78
Heart attack 6.2% 6.3% HR 0.98, 95%CI [0.84 - 1.15], p=0.85
Stroke 0.3% 0.4% HR 0.84, 95%CI [0.43 - 1.64], p=0.62
Major bleeding 4.6% 3.8% HR 1.23, 95%CI [1.01 - 1.49], p=0.04

Findings: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding.
StraightHealthcare analysis
  • The POISE-2 study found that perioperative aspirin did not improve outcomes in high-risk cardiovascular patients undergoing noncardiac surgery. Perioperative aspirin did increase the risk of major bleeding.
  • The results of this study contradict current ACCP guidelines which recommend that patients on aspirin who are at "moderate to high risk" for cardiovascular disease continue aspirin when they undergo noncardiac surgery
ATACAS trial - Stopping vs Continuing Aspirin Before CABG, NEJM (2016) [PubMed abstract]
  • The ATACAS trial enrolled 2100 patients at increased risk for complications who were scheduled to undergo CABG (on-pump or off-pump) with or without valve replacement
Main inclusion criteria
  • Increased risk for major complications related to age or coexisting conditions
  • Not taking aspirin regularly before the trial or had stopped taking aspirin at least 4 days before CABG surgery
Main exclusion criteria
  • Warfarin or clopidogrel within 7 days of surgery
  • Thrombocytopenia or bleeding disorder
  • CrCl < 25 ml/min
  • History of thromboembolism
Baseline characteristics
  • Average age 66 years
  • Heart attack within 90 days - 7.5%
  • Received aspirin within 7 days of surgery - 43%
  • Median number of grafts - 3
  • On-pump surgery - 97%
  • CABG + valve surgery - 20%
Randomized treatment groups
  • Group 1 (1047 patients) - Aspirin 100 mg one to two hours before surgery
  • Group 2 (1053 patients) - Placebo
  • Aspirin was administered to all patients postoperatively at a median time of 18.5 hours after surgery
  • The trial had a 2 X 2 factorial design where half the patients received tranexamic acid (an antifibrinolytic agent)
Primary outcome: Composite of death and thrombotic events (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) during the initial 30 postoperative days
Results

Duration: 30 days
Outcome Aspirin Placebo Comparisons
Primary outcome 19.3% 20.4% RR 0.94, 95%CI [0.80 - 1.12], p=0.55
Major hemorrhage leading to reoperation 1.8% 2.1% p=0.75
Cardiac tamponade 1.1% 0.4% p=0.08
Blood transfusion within 24 hours after surgery 43.9% 42.6% RR 1.03, 95%CI [0.93 - 1.14], p=0.57
  • No interaction was observed between aspirin and tranexamic acid either for the primary outcome or bleeding outcomes

Findings: Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo.
StraightHealthcare analysis
  • The ATACAS trial found no benefit or harm of continuing aspirin before CABG surgery
  • The trial had a 2 X 2 factorial design that also compared tranexamic acid (an antifibrinolytic agent) to placebo. This could have affected the results, although no interaction between tranexamic acid and aspirin was observed.
  • Aspirin was stopped 4 days before surgery, and it's possible some patients in the placebo group still had some antiplatelet effect from aspirin that was taken prior to 4 days (43% of patients received aspirin within 7 days of surgery). This would bias the study toward the null.
  • Although slightly flawed, the ATACAS trial found that preoperative aspirin had no effect on CABG outcomes in patients at increased risk for complications


Procedure bleeding risk
Bleeding risk of Ultrasound-guided Thoracenteses while taking DOACs or Clopidogrel, Mayo Clin Proc (2019) [PubMed abstract]
  • Design: Retrospective case series in patients who underwent ultrasound-guided thoracenteses while receiving DOACs (N=43) or clopidogrel (N=69)
  • Primary outcome: Any significant post-procedure bleeding complication; defined as a hemoglobin decrease of greater than 2 g/dL in 48 hours, hemothorax, chest wall hematoma, and bleeding requiring transfusion, surgery, or chest tube placement
  • Results:
    • Primary outcome: All patients used either the DOAC or clopidogrel within 24 hours before the procedure and continued using it daily thereafter. There were no bleeding complications.
  • Findings: The overall risk of significant hemorrhage in patients taking an NOAC and/or clopidogrel while undergoing ultrasound-guided thoracentesis is very low. Albeit the total number of procedures reviewed may be insufficient to prove definitive safety, it is sufficient to provide a measure of relative risk when assessing benefits of thoracentesis in these patients.
Cold Snare Polypectomy with Continuous Anticoagulants vs Hot Snare Polypectomy with Heparin Bridging, Annals of Internal Medicine (2019) [PubMed abstract]
  • Design: Randomized controlled trial (N=184 | length = 28 days) in patients receiving anticoagulants who had at least 1 nonpedunculated subcentimeter colorectal polyp
  • Treatment: Cold Snare Polypectomy + Continuous Anticoagulants (CSP+CA) vs Hot Snare Polypectomy with Periprocedural Heparin Bridging (HSP+HB)
  • Primary outcome: Incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis)
  • Results:
    • Primary outcome: CSP+CA - 4.7%, HSP+HB - 12% (difference +7.3%, 95%CI [-1.0% to 15.7%])
  • Findings: Patients having CSP+CA for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HSP+HB
Arthrocentesis and Joint Injection in Patients Receiving Direct Oral Anticoagulants, Mayo Clin Proc (2017) [PubMed abstract]
  • Design: Case series (N=1050)
  • Exposure: Patients receiving direct oral anticoagulants (DOACs) who underwent joint aspirations and/or injections
  • Primary outcome: Bleeding complications
  • Findings: In 1050 consecutive procedures, there were no bleeding complications. Arthrocentesis and joint injections in patients receiving DOAC therapy are safe procedures, and there is no need to withhold anticoagulation treatment before the procedure.
Safety of Lumbar Puncture (LP) Performed on Dual Antiplatelet Therapy (DAPT), Mayo Clin Proc (2018) [PubMed abstract]
  • Design: Case series (N=100, length = 3 months)
  • Exposure: Patients receiving DAPT who underwent lumbar puncture
  • Primary outcome: Number of traumatic and bloody cerebrospinal fluid results as well as the presence of any complications occurring within 3 months of the procedure
  • Findings: No serious complications occurred. Cerebrospinal fluid analysis was consistent with a traumatic LP, defined as having at least 100 RBCs/mcl, in 8% of cases. Bloody LP, defined as having 1000 RBCs/mcl, occurred in 4% of cases. The percentage of traumatic or bloody LPs was within the range reported previously for LPs performed in any setting. Although this is a small study and additional review is necessary, performing LPs in the setting of dual antiplatelet therapy may not pose an increased risk of serious complications.