Perioperative Bridging in Atrial Fibrillation: Is it necessary?

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1 Perioperative Bridging in Atrial Fibrillation: Is it necessary? Jason B. Thompson M.D., Ph.D. August 29, NCVH Birmingham

2 Hypothesis: When bridging, risk of bleeding < risk systemic embolism (SE). Rationale: Risk of SE compounded by prothrombotic state of having had surgery and rebound hypercoaguability of having stopped coumadin.

3 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation Bridging therapy with unfractionated heparin or lowmolecular-weight heparin (LMWH) is recommended for patients with AF and a mechanical heart valve undergoing procedures that require interruption of warfarin. Decisions on bridging therapy should balance the risks of stroke and bleeding.

4 2.1. In patients who require temporary interruption of a VKA before surgery, we recommend stopping VKAs approximately 5 days before surgery In patients who require temporary interruption of a VKA before surgery, we recommend resuming VKAs approximately 12 to 24 h after surgery In patients with a mechanical heart valve, atrial fibrillation, or VTE with a thromboembolic risk that is HIGH Bridge LOW No bridging Moderate Individualize depending upon patient and procedure related risk Chest 2012;141;e44S-e88S

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6 Country distribution of mean time in therapeutic range in the RE-LY trial WWU Münster Lars Wallentin et al., Lancet 2010; 376:

7 GOALS Prevalence of atrial fibrillation Importance OAC Reality of treatment interruptions Evidence for bridging

8 Prevalence of Diagnosed AF Stratified by Age and Sex Women Men < > 85 x-axis = % y-axis = # of men/women # Women # Men Go AS, JAMA May 9;285(18): Pub Med PMID:

9 Incidence of AF Lifetime Risk for AF at Selected Index Ages by Sex Index Age, yrs Men Women % ( ) 23.0% ( ) % ( ) 23.2% ( ) % ( ) 23.4% ( ) % ( ) 23.0% ( ) % ( ) 21.6% ( ) 1 in 4 Men & women >40 Years will develop AF Lifetime risk if currently free of AF Lloyd-Jones DM, et al. Circulation Aug 31;110(9): Pub Med PMID:

10 Patients with atrial fibrillation (millions) The AF epidemic Mayo Clinic data (assuming a continued increase in the AF incidence) Mayo Clinic data (assuming no further increase in the AF incidence) ATRIA study data Year

11 What is the link between atrial fibrillation and stroke? People with atrial fibrillation are five times more likely to have a stroke: % of strokes are related to atrial fibrillation 2 Up to three million people worldwide have an atrial fibrillation-related stroke every year that is one person every 12 seconds! Fuster V, Rydén LE, Cannom DS, et al. Circulation 2006; 114:700-52; 2. The Copenhagen Stroke Study. Jørgensen HS, Nakayama H, Reith J, et al. Stroke. 1996;27: ; 3. Wolf PA, Abbott RD, Kannel WB. Stroke 1991; 22(8):983-8; 4. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke 1996; 27:1760-4; 5. Atlas of Heart Disease and Stroke, World Health Organization, September Viewed July 2009 at ttp://

12 Scoring Systems in Atrial Fibrillation Given that anticoagulant therapy has both risks (principally bleeding) and benefits (a reduced risk of thrombosis) scoring systems have been produced to estimate the risk of these outcomes No one scoring system is universally accepted or highly predictive (in individual patients)

13 Scoring Systems in Stroke Risk A variety of systems have been published Outlined on next slide All use selected clinical characteristics to predict the risk of stroke Most widely used is the CHADS 2 score All scores provide a rough estimate of risk of thrombosis in a population at similar risk as patient being reviewed

14 Atrial Fibrillation Risk Stratification 12 Schemes applied to 1000 patients from SPAF III study High Moderate Low Stroke Risk in Atrial Fibrillation Working Group. Stroke Jun;39(6): Pub Med PMID:

15 CHA 2 DS 2 -VASc 2009 Birmingham Schema Expressed as a Point-Based Scoring System Risk Factor Congestive heart failure/lv dysfunction 1 Hypertension 1 Age 75 y 2 Diabetes mellitus 1 Stroke/TIA/TE 2 Vascular disease myocardial infarction, peripheral artery disease, or aortic plaque) (prior Age y 1 Sex category (i.e. female gender) LV = left ventricular; TE = thromboembolism Score 1 1 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest Feb;137(2): Pub Med PMID:

16 CHA 2 DS 2 -VASc and CHADS 2 Score 0 1 Refines stroke risk stratification in AF patients: nationwide cohort 1 Year Follow-up 12 Years Follow-up Person Yrs Events Stroke rate (95%CI) Person Yrs Events Stroke rate (95%CI) CHADS 2 score ,272 1, ( ) 187,200 4, ( ) CHA 2 DS 2 -VASc = 0 6, ( ) 39, ( ) CHA 2 DS 2 -VASc = 1 8, ( ) 45, ( ) CHA 2 DS 2 -VASc = 2 11, ( ) 51,595 1, ( ) CHA 2 DS 2 -VASc = 3 11, ( ) 45,799 1, ( ) CHA 2 DS 2 -VASc = 4 1, ( ) 4, ( ) CHADS 2 score = 0 17, ( ) 92, ( ) CHA 2 DS 2 -VASc = 0 6, ( ) 39, ( ) CHA 2 DS 2 -VASc = 1 6, ( ) 35, ( ) CHA 2 DS 2 -VASc = 2 3, ( ) 16, ( ) CHA 2 DS 2 -VASc = ( ) 1, ( ) CHADS 2 Score = 1 22,945 1, ( ) 94, ( ) CHA 2 DS 2 -VASc = 1 2, ( ) 10, ( ) CHA 2 DS 2 -VASc = 2 8, ( ) 34, ( ) CHA 2 DS 2 -VASc = 3 11, ( ) 44, ( ) CHA 2 DS 2 -VASc = 4 1, ( ) 4, ( ) Olesen JB, Torp-Pedersen C, Hansen ML, Lip GY. Thromb Haemost Jun;107(6): Pub Med PMID:

17 Stroke Prevention in Atrial Fibrillation Adjusted-dose warfarin compared with placebo or control Relative Risk Reduction (95% CI) Study Year AFASAK I 1989; 1990 SPAF I 1991 BAATAF 1990 CAFA 1991 SPINAF 1992 EAFT 1993 All trials (n=6) N=2,900 Ann Intern Med 2007; 146: % 50% 0-50% -100% Favors Warfarin Favors Placebo or Control Adjusted dose warfarin and antiplatelet agents have been shown to reduce the risk of stroke compared with control by 64%.

18 Treatment Interruption (TI) of Anticoagulation in Patients with NVAF Common, occurring in >250,000 patients in the US alone Rocket AF: 4700 patients with > 7000 TI generally < 5d [6% bridged] 30-d stroke/se 0.4% (comparable in the rivaroxaban and coumadin groups) but greater than the 0.2% rate in the 14, 236 Rocket-AF patients Matthew W. Sherwood et al. Circulation. 2014;129:

19 Increased short-term risk of thromboembolism or death after TI in patients with atrial fibrillation 72% patients experienced a TI with a three-fold increase in risk of thromboembolic event or death in first 90 days European Heart Journal (2012) 33,

20 THROMBOEMBOLIC EVENTS OVERALL BLEEDING EVENTS Deborah Siegal et al. Circulation. 2012;126:

21 Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation from the ORBIT-AF Registry (n=10,132 median follow-up 2 y) Overall No Bridging Bridging p (n=2280) (n=1766) (n=514) Any adverse event during TI 3.4 (77) 2.8 (50) 5.3 (27) 0.01 Bleeding Event 2.2 (50) 1.8 (31) 3.7 (19) 0.02 Thrombotic Event 0.6 (13) 0.5 (9) 0.8 (4) 0.5 Other Adverse Event 0.6 (14) 0.5 (9) 0.8 (4) 0.6 Events within 30d TI MI 0.2(5) 0.2 (4) 0.2(1) 0.9 Stroke or SE 0.4(8) 0.3 (5) 0.6 (3) 0.3 Major Bleeding 1.7 (38) 1.2 (20) 3.8 (18) Hospitalization Cardiovascular 2.7 (59) 2.2 (38) 4.2 (21) 0.02 Bleeding 1.0 (23) 0.7 (12) 2.2 (11) Other 3.1 (69) 2.8 (49) 4.0 (20) 0.2 Death 0.2 (4) 0.2 (3) 0.2 (1) 0.9 Circulation.2015; 131:

22 The Bridge Trial Randomized double-blind, placebo-controlled trial of 1884 patients with a mean age of 72 and a mean CHADS2 = % had a CHADS2 >3 Randomized to bridging (n=934) with dalteparin (100 IU/kg) bid from 3 days until 24 hrs before the elective procedure and again to 5-10 days post procedure versus no-bridging (n=950) 30 day incidence arterial thromboembolism 0.4% in the no-bridging arm and 0.3% in patients bridged with LMWH (p=0.01 for noninferiority) 12 major bleeding events occurred in the no-bridging arm compared with 29 major bleeds in the bridging arm (1.3% vs 3.2%, p=0.05) N Engl J Med 2015; 373:

23 National Trends in Ambulatory Anticoagulation Use ( ) Direct oral anticoagulants introduced in 2010 Four agents currently available for the treatment of nonvalvular atrial fibrillation and venous thromboembolism Between , DOAC use has grown to 38% of treatment visits where patients are prescribed anticoagulation

24 Pharmacokinetics of NOACs Apixaban Dabigatran Rivaroxaban Direct factor inhibition Xa IIa Xa Bioavailability (F rel ) 80% 6% 80% Peak action (t max ) 1 3 hr 1 3 hr 1 3 hr Protein binding 84% 35% 92 95% Renal clearance 25% 80% 33% Elimination half life with creatinine clearance > 80 ml/min Elimination half life with creatinine clearance ml/min Elimination half life with creatinine clearance ml/min Elimination half life with creatinine clearance < 30 ml/min 15.1 hr 13.8 hr 8.3 hr 14.6 hr 16.6 hr 8.7 hr 17.6 hr 18.7 hr 9.0 hr 17.3 hr 27.5 hr 9.5 hr Kaatz S, et al. Am J Hematol May;87 Suppl 1:S Pub Med PMID:

25 Meta-analysis of Efficacy and Safety of New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients All cause stroke/see Ischemic and unspecified stroke Hemorrhagic stroke Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Am J Cardiol Aug 1;110(3): Pub Med PMID:

26 Meta-analysis of Efficacy and Safety of New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban vs. Warfarin in AF patients Major bleeding Intracranial bleeding GI Bleeding Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Am J Cardiol Aug 1;110(3): Pub Med PMID:

27 Summary Incidence and prevalence AF will increase significantly in the coming years Anticoagulation of AF is underutilized but paramount Treatment interruptions will be common No indication for bridging anticoagulation in those patients maintained on VKA More data is needed for patients maintained on DOACS