Preventing Stroke in Atrial Fibrillation: Pharmacist Roles in - PowerPoint PPT Presentation

Preventing Stroke in Atrial Fibrillation: Pharmacist Roles in Optimizing Therapy and Ensuring Patient Safety William E. Dager, Pharm.D., BCPS (AQ- Cardiology), FCCP , FCSHP , FCCM, FASHP UC Davis Medical Center Sacramento, California

Disclosures • The following faculty and planners report no relationships pertinent to this activity – William E. Dager, Pharm.D., BCPS (AQ-Cardiology), FCCP, FCSHP, FCCM, FASHP, Faculty – James S. Kalus, Pharm.D., BCPS (AQ-Cardiology), FASHP, Faculty – Angela R. Raval, Pharm.D., Staff – Carla J. Brink, M.S., B.S.Pharm., Staff ASHP Advantage staff have no relevant financial relationships to disclose

Learning Objectives ‒ Assess or reassess the need for anticoagulation therapy and bleeding risk in patients with atrial fibrillation. ‒ Recommend an appropriate target-specific oral anticoagulant for patients with atrial fibrillation, based on critical differences among the options and patient needs. ‒ Develop a plan for ongoing assessment of patients with clinical challenges who are receiving oral anticoagulation for atrial fibrillation.

Atrial Fibrillation (AF) • Most common arrhythmia in U.S. – 9% of patients over age 65 years in the U.S. • Prevalence increases with age • Risk factors – Age – Hypertension (HTN) – Heart failure (HF) • Complications: frequent hospitalizations, hemodynamic abnormalities, and thromboembolic events January CT et al. J Am Coll Cardiol. 2014 Mar 28. [Epub ahead of print]

Stroke in AF • AF → Stroke risk 5x higher • Stroke risk increases with age • AF-related stroke frequently more severe January CT et al. J Am Coll Cardiol. 2014 Mar 28. [Epub ahead of print]

Impact of AF on Cost of Treating Stroke Mean Cost Per Patient Patients with AF Patients without AF Acute hospitalization $7190 ± 4439* $5838 ± 3662 Readmission $1936 ± 5908 $1118 ± 4256 Inpatient rehab $2058 ± 3637 $1733 ± 2809 Total direct costs $15,575 ± 10,945* $11,638 ± 9571 *p<0.05 ‒ Indirect costs (due to loss of productivity) accounted for 18% of total costs ‒ But what about the impact on quality of life? Brüggenjürgen B et al. Value Health. 2007; 10:137-43.

Therapy Considerations • Rate and/or rhythm control - Antithrombotic therapy - Regulatory considerations • Clinical quality measures (VTE prophylaxis) • Stroke core measures • Joint Commission: (2012) Extra care for blood thinners • Management of co-morbidities

Regulatory Considerations Measure Description STK - 1 Ischemic/hemorrhagic: venous thromboembolism (VTE) prophylaxis received or documentation why not the day of and day after hospital admission STK – 2 Ischemic: discharged on antithrombotic therapy (no preferred agent, includes new oral anticoagulants) STK - 3 Ischemic stroke with AF: prescribed anticoagulation therapy at hospital discharge (new anticoagulants included) STK - 4 Acute ischemic stroke arriving within 2 hours of onset: IV-tPA (tissue plasminogen activator) initiated within 3 hours of stroke onset STK - 5 Ischemic stroke received antithrombotic therapy by end of hospital day 2 STK - 6 Discharged on statin medication STK - 8 Stroke education provided STK - 10 Assessed for rehabilitation Related CQM for 2014 - STK 2, STK3, STK 4 (must report 16 of the 29) http://www.jointcommission.org/assets/1/6/Stroke.pdf (accessed 2014 Jun 25).

Question Which of the following are included in the CHA 2 DS 2 -VASc, but not CHADS 2 ? a. Female gender b. Prior myocardial infarction (MI) c. Age 65-74 years d. All the above

AF Anticoagulation: Risk/Benefit Assessment Risk for Thrombosis • Stroke Risk Assessment ‒ CHADS 2 ‒ CHA 2 DS 2 -VASc ‒ Other factors not included - e.g. Thrombus seen on echo (Smoke), renal impairment • Other Indications for Anticoagulation Risk for Bleeding Event • Scoring ‒ HAS-BLED ‒ HEMORR 2 HAGES • Presence of Antiplatelet Agents • Fall Risk

Stroke Risk Stratification in AF CHADS 2 CHA 2 DS 2 -VASc CHADS 2 CHA 2 DS 2 - VASc Heart Failure (1) CHF/LV dysfunction (1) 2 (4/100 pt 2 Hypertension (1) Hypertension (1) years) (2.2%/yr) Age ≥ 75 years (1) Age ≥ 75 years (2) 4 (8.5/100 4 pt years) (4%/yr) Diabetes (1) Diabetes (1) Stroke/TIA (2) Stroke/TIA (2) Vascular disease (1) [Prior MI, PAD, or aortic plaque] Age 65 – 74 years (1) Sex Female (1) TIA = transient ischemic attack PAD = peripheral artery disease LV = left ventricular Gage BF et al. JAMA. 2001; 285:2864-70. Lip GYH et al. Stroke. 2010; 41:2731-8.

2014 AHA/ACC/HRS Atrial Fibrillation Guidelines Risk Category Recommendation CHA 2 DS 2 -VASc = 0 No therapy CHA 2 DS 2 -VASc = 1 OAC or ASA or no therapy CHA 2 DS 2 -VASc ≥ 2 OAC Dabigatran, rivaroxaban, or apixaban Unstable INR OAC = oral anticoagulant = warfarin, dabigatran, rivaroxaban, apixaban ASA = aspirin January CT et al. J Am Coll Cardiol. 2014 Mar 28. [Epub ahead of print]

Major Hemorrhage in AF: HEMORR 2 HAGES • Hepatic or renal disease • Ethanol abuse • Malignancy • Older (> 75 years) • Reduced platelet count/function • Rebleeding risk (2 points) • Hypertension (uncontrolled) • Anemia • Genetic factors (CYP2C9 polymorphisms) • Excessive fall risk Any  5 Total Points 0 1 2 3 4 Score • Stroke Adjusted Risk 1.9 2.5 5.3 8.4 10.4 12.3 18.2 *CYP=cytochrome P450 Bleeds per 100 patient years Gage et al. Am Heart J. 2006; 151:713-9.

HAS-BLED Score for Estimating Bleeding Risk in AF n = 3,665 patients taking warfarin from SPORTIF cohort Events Score Major Bleeding H: HTN 1 point 0 points 0.9% A: Abnormal renal/liver function 1 point each 1 point 3.4% S: Stroke 1 point 2 points 4.1% B: Bleeding history/predisposition 1 point 3 points 5.8% L: Labile INR (TTR <60%) 1 point 4 points 8.9% E: Elderly (>65 yr) 1 point 5 points 9.1% D: Drugs † /alcohol 1 point each TOTAL † Antiplatelets, NSAIDS, or steroids TTR - time in therapeutic range Lip GYH et al. J Am Coll Cardiol. 2011; 57:173-80.

Case: Atrial Fibrillation (CHA 2 DS 2 -VASc score = 4) • 85-year-old female patient • New onset AF > 48 hours • ESRD on hemodialysis • Cardiac stent placed 8 weeks ago ‒ Taking clopidogrel 75 mg daily and aspirin 325 mg daily

Case Discussion Questions • Would this patient’s stroke risk be high enough for anticoagulation? • What agents (including doses) could be used for stroke prophylaxis? • How would you manage risk associated with the need for antiplatelet therapy?

Anticoagulant Sites of Action on the Common Pathway Extrinsic activation pathway Intrinsic activation pathway VII VKA IX VKA X X Direct Xa Inhibitors (Free and bound Xa) Xa Indirect Xa Inhibitors Rivaroxaban , Apixaban, UFH, LMWH Edoxaban Fondaparinux Direct Thrombin Inhibitors Dabigatran, Argatroban Thrombin Prothrombin Bivalirudin, Lepirudin VKA Fibrin Fibrinogen Clot Formation

Facilitating Optimal Antithrombotic Therapy • Cost of therapy (coverage and copay) • Management support • Adherence • Compliance with follow up • Other indications for anticoagulation • Drug/food interactions – Including antiplatelet agents • Organ function (kidneys, liver) • Quality of life • Success/failure of past therapies • Bleeding risks/needs for reversal

Question Which statement is true? a. Opened dabigatran capsules have no impact on bioavailability b. RE-LY assessed dabigatran 75 mg dosing for renal dysfunction c. Rivaroxaban renal dose adjustment depends on indicated use d. Treat paroxysmal AF more aggressively with antithrombotic therapy than persistent AF

AHA/ACC/HRS 2014 Recommendations I C Individualized antithrombotic therapy (stroke, bleeding, patient values/preferences) I B Antithrombotic selection based on thromboembolism risk, not type of AF I B CHA 2 DS 2 ‐ VASc score preferred I B Use warfarin if mechanical heart valve present (Avoid dabigatran [III B]) I A Warfarin: INR weekly initially, then monthly I C Unable to maintain Tx INR on warfarin ‐ use dabigatran, rivaroxaban, apixaban I C Periodic revaluation for stroke to bleeding risk I C AF and mechanical heart valve and procedure: Bridge UFH, LMWH based on risk of thrombosis and bleeding I B Assess renal fxn initially and periodically when using for DTI or anti ‐ Factor Xa agent I C Atrial flutter therapy same as atrial fibrillation IIa B CKD ‐ CrCl < 15 mL/min or hemodialysis – warfarin preferred (NOAC not recommended [III C]) IIb C CKD – Moderate to severe + CHA2DS2 ‐ VASc ≥ 2 – reduced dose NOAC – safety/efficacy unknown IIb C PCI required – Consider Bare Metal Stent to minimize dual antiplatelet therapy Can interrupt during PCI UFH – Unfractionated heparin, LMWH – Low molecular weight heparin, INR – International January CT et al. J Am Coll Cardiol. 2014 Mar 28. [Epub ahead of print] Normalized Ratio, fxn – function, DTI – direct thrombin inhibitor, CKD – chronic kidney disease, PCI- percutaneous coronary intervention; NOAC – New oral anticoagulant