1. Question: How should we manage periprocedural anticoagulation? Paper: Management of Antithrombotic Therapy in Patients Undergoing Invasive Procedures Todd H. Baron, M.D., Patrick S. Kamath, M.D., and Robert D. McBane, M.D. N Engl J Med 2013; 368:2113-2124May 30, 2013DOI: 10.1056/NEJMra1206531May 30, 2013 LSU IM Journal Club 8/20/2014 Benji Morehead

2. Weigh risk on thrombosis vs risk of perioperative bleeding. Differs from condition to condition and procedure to procedure Afib: CHADS/CHADSVASC2 score- risk stratification Mechanical heart valves: type, number, location and thrombotic history VTE: elevated for 3 months, provoked vs nonprovoked Cancer: increased risk due to treatment, increased bleeding 2/2 prophylaxis Stents: BMS vs DES: BMS: highest risk within 6 wks. Up to 12 months antiplatelet. DES: 3-6 months. 12 month minimum antiplatelet Thrombotic risk varies Low risk- <1.5% chance of bleeding High risk- >1.5% chance of bleeding or possibility of intracranial, intraocular, intraspinal, intrathoracic, pericardial, or retroperitoneal bleeds Bleeding Severity for Procedures

4. Bridging Thearapy Thought to give best combo of lower bleeding and thrombosis risk. Considered standard of care, but only evaluated in 2 randomized controlled trials. Rates of thrombosis ~1-2% without bridging Bleeding rates ~2-2.7% with OR without bridging Recent studies suggests periprocedural heparin actually worsens risks of bleeding in moderate to high thromboembolic risk patients (16% heparin bridge vs 3.5% coumadin only). (Meta analysis of 35 studies)

5. Proposed administration and timing of bridging Stop warfarin 5 days before high risk procedure Start LMWH when INR below therapeutic AFIB and mechanical valve: 1mg/kg Enoxaparin q12h or Daltaperin 100IU/kg q12h VTE: Dosages increased to 1.5mg/kg and 200IU/kg respectively Stop 24 hours prior to surgery, check INR morning of surgery Restart warfarin immediately after hemostasis, restart LMWH within 48 hours post-surgery, discontinue once INR therapeutic (~5 days) Timing varies between long term anticoagulant used Warfarin- INR normalizes ~5 days, UFH 3-4 hours, Xa inhibitors (varies, hold 1-2 days longer than package insert suggests)

7. Antiplatelets and “Other” Anti-platelet agents Low dose ASA not associated with increased bleeding Dypyridamole has same characteristics, but is held “before certain elective high risk procedures” Aggrenox (ASA/dypyridamole)-”Probably does” increase bleeding risk. Cilostazol- no increased risk of bleeding, stop 2 days for normalization of platelet fxn. Clopidogrel, ticagrelor- stop taking 5-7 days prior to procedure Ticlopadine- stop 10 days prior to procedure Fondiparinux: acceptable risk in cardiac procedures if stopped 36 hours prior to surgery. Direct Xa inhibitors : hold 1-2 days longer than package inserts suggest IVC filters Not recommended for routine use Have a place only in VTE patients within 4 weeks of starting antithrombotics

8. Reversal of Antithrombotics Reversable Warfarin- INR normalized in 24-48 hours with IV Vit K or FFP Prothrombin complex preferred in pt’s with fluid overload issues UFH- protamine. Also partially reverses LMWH “Non-reversible” Xa inhibitors- no proven reversal therapy Dabigatran- can consider hemodialysis or charcoal perfusion Rivaroxaban- PCC??? (one study, double blind, placebo controlled, 12 healthy patients)

9. Resuming therapy Full dose heparin held 48 hours after procedure (sooner if risk of bleeding considered low enough) Warfarin started day of procedure Unless high rebleed or re-operation likely Clopidogrel- maintenance dosage ok within 24 hours, NO loading. ticegralor and prasugrel- “recommend caution” due to fast onset, strength, and lack or reversal Dabigatran, Rivaroxaban, Apixiban- wait 48 hours due to quick onset ASA, “other antiplatelet agents”- within 24 hours GI procedures (“hot” polypectomy/sphincterotomy)are exception to these rules. May need to hold to prevent delayed bleeding, but often impractical

10. Summary of Recommendations/Conclusions Individualize treatment to patient(meta analysis of 48 reviews) Delay until lower risk time whenever possible Avoid overly aggressive reinstatement of antithrombotic therapy For low risk procedures, anticoagulation can be continued For high risk procedures with low risk thrombosis, temporarily DC antithrombotic with or without bridging. For high risk procedures with high risk of thrombosis, DC with bridging strongly recommended. For recent (<3m) VTE, delay all elective procedures If medically necessary procedure, DC, bridge, place IVC filter if <1 month since started antithrombotics Dual antiplatelet therapy High risk of bleeding- ideally delay until 12 mo therapy Delay with BMS for 6 weeks or 6 months with DES Theinopyridine- temporarily DC if >6weeks BMS or >6mo DES Low bleeding risk Full dose antiplatelet should be continued. ASA: never DC

11. Cautions and Limitations Review article does poor job of categorizing levels of evidence Does not consistently report what evidence the recommendations are based on. GRADE or other quality of evidence reporting Could lead to difficulty in convincing to follow our recs when consulted Some recommendations admittedly not based on good evidence Xa inhibitors rivaroxaban/apixaban (due to lack data) Bleeding risk and severity NOT truly standardized Systemic problem Severity grading uses a hybrid of Am Soc. Gastrointestinal Endoscopy and recs from an article in J of Trombosis and Hemostasis 2005. Bleeding risk based on both guidelines AND expert opinion Imperfect, leads to controversy Ex: diagnostic angiography, GI stent placement, endobronchial FNA, airway stent placement