Question: How should we manage periprocedural anticoagulation?

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/NEJMra1206531 LSU IM Journal Club 8/20/2014 Benji Morehead

2. Thrombotic risk varies • Weigh riskon 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 vsnonprovoked • 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 Bleeding Severity for Procedures • 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

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 warfarin5 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 • Dypyridamolehas 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