3 23 Anticoagulation DMcDanel - Pre-Class Student.pdf

ANTICOAGULATION: FOCUS ON INDICATIONS Deanna McDanel, PharmD, BCPS, BCACP Clinical Pharmacy Specialist, Ambulatory Care Clinical Associate Professor 2022 OVERVIEW – Pre-Recorded Sessions n Part 1 ¡ ¡ n Part 2 ¡ ¡ n Atrial Fibrillation and Atrial Flutter (AF) Part 5 ¡ ¡ n Thrombophilias P...

ANTICOAGULATION: FOCUS ON INDICATIONS Deanna McDanel, PharmD, BCPS, BCACP Clinical Pharmacy Specialist, Ambulatory Care Clinical Associate Professor 2022 OVERVIEW – Pre-Recorded Sessions n Part 1 ¡ ¡ n Part 2 ¡ ¡ n Atrial Fibrillation and Atrial Flutter (AF) Part 5 ¡ ¡ n Thrombophilias Part 4 ¡ n Prevention and Treatment of VTE Assessing Bleeding Risk Part 3 ¡ n Review of Thrombosis Venous Thromboembolism (VTE) – Deep venous thrombosis (DVT) and Pulmonary embolism (PE) Please note slides with an asterisk (*) and bolded/colored/underlined text are to help you know what is important and may be used to test concepts Heart Valve Replacement Left Ventricular Assist Devices (LVADs) and Watchman Device Part 6 ¡ Treatment Guidelines 2 OBJECTIVES 1. Understand the pathophysiology of thrombosis and the clotting cascade. 2. Differentiate between the various indications for anticoagulation (DVT, PE, thrombophilias, atrial fibrillation/flutter, and heart valve replacement). 3. Identify risk factors associated with VTE. 4. Recommend a target international normalized ratio (INR) range and duration of warfarin for the various indications. 5. Understand the recommendations for anticoagulation therapy based on the current CHEST Guidelines. 3 OVERVIEW – PART 1 n Review of Thrombosis n Venous Thromboembolism (VTE) ¡ ¡ ¡ Risk factors for VTE Deep venous thrombosis (DVT) Pulmonary embolism (PE) 4 THROMBOSIS n Thrombosis: formation of blood clots inside vessels ¡ ¡ Normal hemostasis = tissue injury → coagulation cascade → fibrinolysis/clot degradation → healing Thromboembolism = No self-regulation of clotting cascade – – n Venous thrombosis if blood flow impaired Arterial thrombosis due to atherosclerotic plaques Embolism: pieces of thrombus break off, travel to distant sites, damaging other organs ¡ ¡ Pulmonary embolism = from deep vein thrombosis Cerebral vessels = from heart valves and atrial fibrillation 5 Clotting Cascade ─ ─ + Fibrin Stabilizing Factor (XIII) + Stabilized Fibrin Blood Clot Self-Regulation 6 Figure adapted from: Dipiro et al. Phramacotherapy: A Pathophysiologic Approach, 3rd Ed. 1997. VENOUS THROMBOEMBOLISM (VTE) 7 Overview of VTE n n True incidence unknown, >50% silent disease ~ 2 million people in US per year (1/1000 persons per year) ¡ n 600,000 are hospitalized and 60,000 die Virchow’s Triad: Physiologic changes in any of 3 factors increase risk for thrombosis ¡ ¡ ¡ Decreased blood flow (i.e. venous stasis) Changes in intrinsic properties of blood (i.e. hypercoagulable states) Vessel injury/inflammation (i.e. surgery, trauma) 8 Etiology of VTE PE 9 Risk Factors for VTE* RISK FACTOR EXAMPLE Estimated RR* Age Risk doubles with each decade after age 50 History of VTE Strongest risk factor for DVT and PE Venous Stasis Major surgery (e.g. general anesthesia >30 minutes) 5-200 Major medical illness (e.g. CHF, MI), hospitalization 5 >50 yo = 5 >70 yo = 10 50 Obesity 1-3 Paralysis (e.g. stroke, spinal cord injury) NP Vascular Injury Major orthopedic surgery (e.g. knee/hip replacement) (Risk increased Trauma (fractures of the pelvis, hip, or leg) >50% in no Indwelling venous catheters prophylaxis) *RR= Relative Risk of VTE in patients with risk factor versus those without risk factors; NP = not provided Adapted from: Dipiro, et al. Table 21–1. Risk Factors for Venous Thromboembolism; NEJM 2004;351:268-77. 5-200 5-200 NP 10 Risk Factors for VTE* (cont.) RISK FACTOR EXAMPLE Estimated RR* Hypercoagulable States Malignancy 5 Pregnancy 7 Thrombophilias (These are also hypercoagulable states) Activated protein C resistance, aka Factor V Leiden Homo 50, Hetero 5 Antithrombin (AT) Deficiency 25 Protein C or S deficiency 10 Antiphospholipid antibodies 2-10 Factor VIII excess or XI excess (>90th percentile) Prothrombin (20210A) gene mutation, aka Factor II Drug Therapy Estrogen OCPs, hormone replacement Selective estrogen-receptor modulators (SERMs) 3 Hetero 2.5 5 OCP; 2 HRT 3-5 *Relative Risk of VTE with risk factor versus without; Homo=homozygous; Hetero=heterozygous; OCP=oral contraceptive pills; HRT=hormone replacement therapy; Adapted from: Dipiro, et al. Table 21–1. NEJM 2004;351:268-77. 11 DEEP VENOUS THROMBOSIS 12 Deep Venous Thrombosis (DVT) n Most common if risk factors for VTE Complications: PE, postphlebitic syndrome (20-50%), dependent edema, loss of limb (uncommon) n Signs and Symptoms: n ¡ ¡ ¡ Often asymptomatic Unilateral leg/arm pain, tenderness, swelling, discoloration, and/or warmth Palpable cord 13 Venous Circulation n n Distal DVT: ~25% extend to proximal veins in 1 wk Proximal DVT: cause 50% of PE and most fatal PEs Proximal Veins Distal Veins 14 DVT: Diagnostic Testing - FYI n n Guidelines suggest use of clinical assessment of pretest probability before performing the same diagnostic tests for all patients D-dimer: by-product of thrombin (>0.5 mcg/ml) ¡ ¡ n Adjunct to diagnostic tests, aids in excluding diagnosis May be increased in non-thrombotic conditions (i.e. infection, elderly, inflammatory conditions, etc) Compression ultrasonography (CUS) ¡ ¡ Aka Doppler: measures rate/direction of blood flow Visualize proximal vein clots (not reliable in distal clots) CHEST 2012; 141(2 Suppl): e351S-e418S. 15 DVT: Diagnostic Testing (cont.) - FYI n Clinical assessment of pretest probability (Wells score) ¡ ¡ ¡ ¡ Low (0 or less): D-dimer, if + confirm with CUS Moderate (1 or 2): D-dimer, if + confirm with CUS High (3 or more): CUS (proximal or whole-leg) More specifics if negative test, recurrent DVT, pregnancy or upper DVT Wells PS et al. Lancet 1997;350(9094): 1795-8. 16 Pictures of DVT Femoral vein clot 17 PULMONARY EMBOLISM 18 Pulmonary Embolism (PE) n n n 3rd leading cause of death in US Most common if risk factors for VTE during or following hospitalization Many develop after symptomatic DVT, some on own ¡ ¡ n > 95% originate from deep veins of the lower extremities < 5% originate from other sources Complications: death, shock, pulmonary hypertension (<1%) ¡ ~60% die within 1 hour (golden hour), if survive mortality decreases (3-8%) 19 PE (cont.) n Signs and Symptoms: ¡ ¡ ¡ ¡ n Nonspecific signs and symptoms Classic Trio: dyspnea, pleuritic chest pain, hemoptysis Other are cough, tachypnea, tachycardia Massive PE: dizziness or light-headedness, hypotension, hypoxia/cyanosis, death Diagnostic Tests: ¡ Computed Tomographic (CT) scan – ¡ Most commonly done clinically Ventilation-Perfusion (V/Q) – Estimates probability of PE – Measures airflow in lungs to distribution of blood n Laboratory Test: Elevated D-dimer (like DVT) 20 Pictures of PE 21 Summary of VTE n n n n VTE comprised of both DVT and PE High incidence, associated with death Know risk factors associated with VTE Most frequent if patient has risk factors: ¡ ¡ ¡ ¡ ¡ ¡ Trauma Surgery Cancer Immobilization Thrombophilias Estrogen 22 OVERVIEW – PART 2 n Venous Thromboembolism (VTE) ¡ ¡ ¡ VTE prevention VTE treatment Bleeding risk – Risk factors – Assessing bleeding risk ¡ Summary 23 Prevention of VTE n n n Major cause of morbidity and mortality Choice of prophylaxis is dependent upon the risk of developing a VTE and/or bleed Rationale for thromboprophylaxis: ¡ ¡ ¡ n High prevalence of VTE Adverse consequences of recurrent VTE Highly effective Non-pharmacologic interventions: ¡ ¡ ¡ Early ambulation Graded compression elastic stockings (GCS) Intermittent pneumatic compression (IPC) 24 Treatment of VTE - Goals n Prevent progression of disease: ¡ ¡ n n Thrombus extension and PE Recurrence of DVT or PE Decrease mortality Prevent post-thrombotic (phlebitic) syndrome (PTS) ¡ GCS x 2 years – ¡ n Not recommended for routine use IPC in severe PTS Cost-effective without treatment adverse effects 25 Treatment of VTE (cont.) n Anticoagulant Therapy ¡ ¡ ¡ Inpatient (high risk VTE) Outpatient (most DVTs and low risk PEs) Options (DOACs preferred): – – – n Inferior vena cava filters ¡ ¡ n Rivaroxaban or apixaban without bridging Dabigatran or edoxaban AFTER 5-10 days of parenteral bridging Heparin/LMWH/others PLUS warfarin Not recommended Only if contraindication to anticoagulation Thrombolysis and thrombectomy 26 Predicting Recurrent VTE – FYI HERDOO2 Used for FEMALES >50 years ONLY (assumes males are high risk) 0-1 LOW Recurrence Risk Discontinue Anticoagulation ≥2 HIGH Recurrence Risk Continue Anticoagulation 27 Rodger MA, et al. BMJ. 2017;356:j1065. Predicting Recurrent VTE – FYI HERDOO2 (Cont.) Risk of VTE Recurrence 3% Low risk who stopped Rodger MA, et al. BMJ. 2017;356:j1065. 8.1% High risk who stopped 1.6% High risk who continued 28 Predicting Recurrent VTE – FYI DASH Used for MALES or FEMALES Best Validated if >65 years Predictor Scoring D D-Dimer >500 ng/mL 4 weeks after stopping anticoagulation 2 A Age <50 years 1 S Sex – Male 1 H Hormone therapy at onset -2 0 2 year recurrence = 5.9% 1 2 year recurrence = 8.4% 2 2 year recurrence = 11.1% Tosetto A, et al. J Thromb Haemost. 2017;15:1963-70. ≥2 HIGH Recurrence Risk Continue Anticoagulation 29 Assessing Bleeding Risk - FYI HAS-BLED Hypertension (Uncontrolled, >160 mmHg systolic) Abnormal liver or renal function (Dialysis, renal transplant, SCr >2.26, chronic hepatic disease, bilirubin >2 x ULN + LFTs >3 x ULN) Score 1 1-2 Stroke history 1 Bleeding predisposition (i.e. anemia) 1 Liable INR (<60% TTR, unstable/high) 1 Elderly (age >65) 1 Drugs or Alcohol Use (Antiplatelets/NSAIDs; >8 drinks/wk) *VALIDATED IN AFIB ONLY Pisters R, et al. Chest 2010; 138(5):1093-100. 1-2 0-2 LOW bleeding risk ≥3 HIGH bleeding risk Modifiable risk factors: • Excessive Alcohol • Uncontrolled HTN • NSAID usage • Liable INRs Summary of VTE n Prevention of VTE is the key Treatment 31 OVERVIEW – PART 3 n Thrombophilias ¡ ¡ ¡ ¡ Inherited versus acquired Testing Treatment Summary 32 THROMBOPHILIAS 33 Thrombophilias n n n n May be INHERITED or ACQUIRED Increased risk of 1st thrombosis 2.5-25x of normal population Prevalence 1%-20% of population (~30% of idiopathic VTE) Testing sometimes done if at time of presentation: ¡ ¡ ¡ ¡ ¡ ¡ n n VTE at early age <50 yo Family history of VTE Recurrent unprovoked thromboembolism Unusual site (i.e. liver, mesenteric, brain, renal) Multiple spontaneous abortions Massive thrombosis Generally testing is NOT done unless changes decision on use of or duration of anticoagulation If on warfarin, wait 10-14 days to test for protein C/S deficiency and possibly ATIII levels ¡ Genetic (FV Leiden or PT gene mutation) tests NOT affected by warfarin 34 Thrombophilias – Testing n n n n Testing for thrombophilias can uncover an abnormality in >60% of patients with 1st VTE Routine testing after VTE is controversial Considerations: cost, interpreting results, VTE management Only test select patients if results will significantly affect management, including: ¡ ¡ ¡ ¡ ¡ Duration and intensity of anticoagulation therapy Therapeutic monitoring strategies Family screening (preventative tests for female relatives) Family planning Choice of concomitant medications (i.e. OCP or HRT) Chon DM et al. Sem Thromb and Hemostasis 2007;33(6):573-81. Patel C et al. Missouri Medicine 2009;106(1):55-9. 35 Thrombophilias – Inherited n Group 1: Mutations that cause increased concentration or change in function of coagulation factors ¡ Factor V Leiden mutation ¡ Prothrombin (Factor II) gene mutation ¡ n Group 2: Coagulation factor disorders ¡ Protein C deficiency ¡ Protein S deficiency ¡ Antithrombin (III) deficiency ¡ Others: elevations in factor VIII, IX and XI ¡ n More common, but weaker risk for thrombosis Not common, but strongly thrombophilic All cause problem with self-regulation of clotting cascade, with exception of Prothrombin gene mutation 36 Factor V Leiden Prothrombin Gene Mutation + ─ ─ + Protein C Def. Protein S Def. Self-Regulation AT Deficiency Figure adapted from: Dipiro et al. Phramacotherapy: A Pathophysiologic Approach, 3rd Ed. 1997. 37 Thrombophilias – Acquired n n Malignancy ¡ Extended LMWH preferred over warfarin Antiphospholipid antibody syndrome (APS) ¡ Clinically important antibodies: – – – ¡ Anticardiolipin antibodies (ACA) - most common Lupus anticoagulant (LA) Anti β2-glycoprotein I antibody (β2GPI) Etiology and mechanism for clotting unknown – Secondary to underlying disease states, infection or medications Probably the most strongly thrombophilic condition ¡ Specific recommendations regarding antepartum and post-partum VTE prevention in pregnancy Others: Acute infection, chronic inflammatory diseases ¡ n 38 Thrombophilias – Treatment n Warfarin mainstay; direct acting agents generally may be used ¡ ¡ n No concrete recommendations for duration of anticoagulation ¡ n Aspirin is better for prevention of arterial clots in APS DOACs NOT used for APS Typically duration for specific thrombosis Considerations for indefinite therapy: ¡ ¡ ¡ ¡ ¡ ¡ ¡ Number, site, severity of thrombosis Transient risk factor or unprovoked Recurrent event Risk of re-thrombosis with particular thrombophilia More than one thrombophilic condition Bleeding risk Patient factors: female gender, lifestyle, compliance, other risk factors, and personal values 39 Thomas RH. Arch Int Med 2001; 161:2433-39. Summary of Thrombophilias n Thrombophilias may be inherited or acquired ¡ ¡ n Testing is not done in all patients with VTE Treat VTE with oral anticoagulation, but little guidance from guidelines on duration of treatment DOACs currently not recommended in antiphospholipid antibody syndrome (especially if triple positive) 40 OVERVIEW – PART 4 n Atrial Fibrillation and Atrial Flutter (AF) ¡ ¡ Pathophysiology Stroke risk stratification – CHA2DS2-VASc ¡ Summary 41 ATRIAL FIBRILLATION & ATRIAL FLUTTER 42 Atrial Fibrillation/Flutter (AF) n n n Irregular contraction of atria → blood pooling → clot formation → embolism→ stroke Most common cardiac rhythm disorder AF increases with age ¡ Increases > 60 yo – ¡ ¡ n ~10% prevalence >80 yo Mean age 72 yo Uncommon if < 50 yo Men > women 43 Atrial Fibrillation/Flutter (cont.) n Primary cause of cardioembolic stroke ¡ ¡ n 15% of all strokes in US Risk of stroke increased 4-6x if AF Stroke risk with AF increases with age/other factors ¡ ¡ 50-59 yo = 1.5%; 80-89 yo = 23.5% Highest: history of transient ischemic attack (TIA) or stroke n Rate of stroke if AF untreated averages 4.5%/yr n Symptoms of stroke: unilateral sudden numbness or weakness, confusion, trouble speaking, vision changes, balance changes, severe headache 44 Stroke Risk Stratification in AF n CHA2DS2-VASc: simple clinically based stroke risk score that identifies ‘low stroke risk’ patients who should not be offered antithrombotic therapy to prevent stroke and reduce mortality n Goal: is to use the tool to help prevent use of anticoagulation in low risk patients n Important to reassess score at every visit 45 Stroke Risk Stratification* (cont.) CHA2DS2-VASc Risk* Score CHA2DS2-VASc Score Adjusted Stroke Rate (%/Year) - FYI 0 0 1 1.3 2 2.2 C = Congestive Heart Failure (or LV systolic dysfunction) 1 H = Hypertension 1 A = Age > 75 years old 2 3 3.2 D = Diabetes mellitus 1 4 4.0 S = Stroke/TIA/Thromboembolism 2 5 6.7 Disease# 1 6 9.8 7 9.6 8 6.7 9 15.2 V = Vascular A = Age 65 - 74 1 Sc = Sex category (Female) 1 #Vascular: prior MI, angina, PCI, CABG; presence of intermittent claudication, prior surgery to abdominal aorta, lower extremity vessels, or abdominal/thoracic surgery; arterial or venous thrombosis Lip GY, et al. Chest. 2010;137(2):263-72 46 TTR in Warfarin Management - FYI SAMe-TT2R2 Acronym Risk Factors Score S Sex = Female 1 A Age <60 1 Medical History ≥2* 1 T Treatment – Drug interactions 1 T Tobacco use (within 2 years) 2 R Race (non-Caucasian) 2 Me (i.e. amiodarone) *Medical Conditions: hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, and hepatic or renal disease 0-2 Likely to achieve TTR ≥2 Less likely to achieve TTR Goal TTR >70% Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 2018;Aug 21. Assessing Bleeding Risk - FYI HAS-BLED Hypertension (Uncontrolled, >160 mmHg systolic) Abnormal liver or renal function (Dialysis, renal transplant, SCr >2.26, chronic hepatic disease, bilirubin >2 x ULN + LFTs >3 x ULN) Score 1 1 Bleeding predisposition (i.e. anemia) 1 Liable INR (<60% TTR, unstable/high) 1 Elderly (age >65) 1 (Antiplatelets/NSAIDs; >8 drinks/wk) *VALIDATED IN AFIB ONLY Pisters R, et al. Chest 2010; 138(5):1093-100. LOW bleeding risk ≥3 HIGH bleeding risk 1-2 Stroke history Drugs or Alcohol Use 0-2 1-2 Modifiable risk factors: • Excessive Alcohol • Uncontrolled HTN • NSAID usage • Liable INRs Summary: Atrial Fib/Flutter n n n Atrial fibrillation/flutter increases the risk for stroke CHA2DS2-VASc is used to score risk of stroke Oral anticoagulation for stroke prevention ¡ Use if CHA2DS2-VASc is >1 for men or >2 for women 0 ¡ ¡ • No anticoagulation DOACs preferred If warfarin used, maintain TTR >70% in range 2.0-3.0 49 OVERVIEW – PART 5 n Heart Valve Replacement ¡ ¡ ¡ ¡ n Left Ventricular Assist Devices (LVADs) ¡ n Position of heart valves Types of valves Antithrombotic treatment in heart valves Summary Brief overview Watchman Device 50 HEART VALVE REPLACEMENT and DEVICES 51 Heart Valve Replacement n n Prosthetic heart valves: mechanical and bioprosthetic Mechanical: increased risk of stroke (0.5 – 2.5% per year) ¡ Clotting dependent on the position of the valve and type of valve MECHANICAL BIOPROSTHETIC All require lifelong warfarin 3-6 months*: Aspirin 75-100 mg/d OR Warfarin (INR 2.5) *If atrial fib also - lifelong AND must use warfarin or DOACs (only when >3 mo from insertion) based on CHA2DS2-VASc Thrombogenic Low thrombogenicity Durable Limited life span Valves last 20-30 yrs 10%-30% fail within 10-15 yrs Preferred in younger patients AND if can take lifelong warfarin Preferred in older patients OR can not take lifelong anticoagulants Otto et al. 2020 ACC/AHA Guideline for the Management of Valvular Heart Disease. JACC 2021;77(4):e25-197 52 Position of Heart Valve n Mitral valves have an increased risk of thrombosis versus aortic valves 53 Types of Valves OPEN CLOSED Mechanical – Old Generation Most thrombogenic valves n Caged Ball - Starr-Edwards n Single Tilting Disc - Bjork-Shiley, Medtronic Hall Mechanical - New Generation n Bileaflet (most common) - St Jude, Carbomedics n Bileaflet (newest) – On-X valve Bioprosthetic Least thrombogenic valves n Human (Homograft, Autograft) n Animal (Bovine, Porcine) n TAVR/TMVR (Transcatheter aortic or mitral valve replacement) 54 On-X® Valve n n n n Bileaflet mechanical heart valve FDA approved in 2001 Study results showed it to be the only mechanical valve proven to be safer with less anticoagulation Warfarin ONLY available anticoagulant ¡ n DOACs are not safe options FDA approved in 2015, lower target range ¡ ¡ For mitral or multiple valves – INR 2.5-3.5 For aortic valve – INR 2.0-3.0 x 3 months, then reduced to 1.5-2.0 (if no additional risk factors) – 65% fewer bleeding events without increase in stroke http://www.onxlti.com/bbb/ 55 Left Ventricular Assist Devices - FYI n n AKA = LVAD Mechanical circulatory support for advanced heart failure n n n Bridge to transplantation OR destination therapy HeartMate II – approved 2008 ¡ ¡ n Unloads ventricle and generates flow to the systemic and/or pulmonary circulation Continuous flow Follows native pulse (pulse not palpable) Heartmate 3 – approved 2018 ¡ ¡ Centrifugal flow Better long-term survival and safety outcomes 56 LVADs (cont.) - FYI n Complications ¡ n n Medical management: standard heart failure treatment Anticoagulation ¡ ¡ ¡ ¡ ¡ n Right ventricular failure , stroke/thromboembolic events, pump thrombosis, hemolysis, infection, bleeding Immediate post-op period: generally none unless afib or thrombus present Post-op day 2 to 5: Warfarin with no bleeding and chest tubes removed Target INR 2.0-3.0 (may be 1.5-2.5 or 2.5-3.5 based on the patient and complications) INRs every 2 weeks Begin aspirin 81 mg to 325 mg daily Monitoring: bleeding (GI), driveline infections, hemolysis 57 WATCHMAN™ Device - FYI n Left atrial appendage (LAA) closure device ¡ ¡ ¡ The LAA is believed to be the main source of clots that cause stroke in non-valvular AF Not intended to replace all oral anticoagulants Eligible patients: – – – CHA2DS2-VASc >2 Suitable for warfarin Appropriate reason to seek non-pharmacologic alternative to warfarin Blackshear JL. Odell JA., Annals of Thoracic Surgery. 1996;61:755-759 WATCHMAN: Left Atrial Appendage Closure Device Overview Presentation. Boston Scientific. 58 WATCHMAN™ Anticoagulation - FYI n Post-procedure warfarin + aspirin is required in ALL patients ¡ n n Stopping warfarin depends on time from implant and seal of blood flow to LAA Clopidogrel with increased aspirin dosing depends on if warfarin is discontinued within 6 months of implantation Remain on aspirin 325 mg indefinitely WATCHMAN: Left Atrial Appendage Closure Device Overview Presentation. Boston Scientific. Summary: Heart Valves n n n Mechanical heart valves increase the risk for stroke Mitral valves are more thrombogenic than aortic valves When to use oral anticoagulation: ¡ ¡ Indefinitely in ALL patients with mechanical heart valves and LVAD patients for stroke prevention Warfarin is ONLY oral anticoagulant option – ¡ ¡ DOACs may have some role in bioprosthetic valves with Afib after 3 months from insertion or TAVR/TMVR; NOT for On-X, mechanical valves or mitral stenosis INR range depends on position of valve Bioprosthetic: aspirin or short course warfarin (depending on type) 60 OVERVIEW – PART 6 n Treatment Guideline Review VTE Atrial Fibrillation Heart Valves 61 Treatment of VTE* Indication: Treatment of VTE (Including DVT and/or PE) Duration of Anticoagulation VTE without contraindications to anticoagulation 3 months 2.0 to 3.0 Unprovoked VTE or provoked by a persistent risk factor Extended-phase 2.0 to 3.0 - DOAC preferred over warfarin - If NO anticoagulation, aspirin preferred over no therapy - Warfarin INR Range Reduced-dose apixaban or rivaroxaban preferred over full dose VTE with minor transient risk factor Suggest no extended-phase 2.0 to 3.0 VTE with major transient risk factor NO extended-phase 2.0 to 3.0 CHEST 2021; 160(6): e545-608. 62 Treatment of VTE CHEST 2021; 160(6): e545-608. 63 Treatment of Atrial Fibrillation* Non-Valvular AF CHA2DS2-VASc Antithrombotic Therapy AF at low risk of stroke 0 (men) 1 (women) NO THERAPY AF at high risk of >1 non-sex risk factors stroke If therapy chosen: Aspirin 75-325 mg/d Oral anticoagulation DOAC recommended over warfarin in eligible patients (NOT for moderate-to-severe mitral stenosis or mechanical heart valves) Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 2018;Aug 21. Circulation 2019;140(2):e125-e151. 64 Treatment of Atrial Fibrillation* n Apixaban or edoxaban: prior unprovoked bleeding, bleeding on warfarin, high bleeding risk (HAS-BLED score of ≥3) ¡ ¡ n Warfarin (INR 2.0-3.0): target time in the therapeutic range [TTR] of >70% ¡ n High risk for bleeding should be followed frequently Survived intracranial hemorrhage at high risk of recurrence à left atrial appendage occlusion TTR <65-70%: intervene to improve control with more frequent INRs, further education, review adherence and drug-drug interactions Apixaban or warfarin: recommended for end-stage CKD (CrCl <15 or dialysis) Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 2018;Aug 21. Circulation 2019;140(2):e125-e151. 65 Treatment for Heart Valves* n Thromboembolic risk factors: ¡ ¡ ¡ ¡ ¡ Older-generation valve Atrial fibrillation Previous thromboembolism Hypercoagulable state LV systolic dysfunction J Am Coll Cardiol. 2021;77:e25–197. 66 Treatment for Heart Valves - FYI TAVI – Transcatheter aortic valve implantation J Am Coll Cardiol. 2021;77:e25–197. 67 Treatment for Heart Valves* MECHANICAL Heart Valves Duration of Warfarin INR Range Aortic mechanical valve no other risk factors Indefinite 2.0 to 3.0 Aortic mechanical valve with risk factors Indefinite 2.5 to 3.5 Mitral mechanical valve Indefinite 2.5 to 3.5 On-X aortic mechanical valve Indefinite 3 months: 2.0-3.0 + ASA 81 mg Ongoing: 1.5-2.0 + ASA 81 mg (if no other risk factors) Mechanical valve at low bleeding ADD Aspirin 50-100 mg/d to indefinite warfarin risk *Direct acting anticoagulants should never be used for anticoagulation of heart valves J Am Coll Cardiol. 2021;77:e25–197. 68 Thank you! Questions: [email protected] 69