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Days of a Heart Valve’s Life The pharmacist’s approach to valvular heart disease Erica Wang BScPharm, PharmD, ACPR, BCPS Clinical Pharmacy Specialist – Cardiac Surgery St. Paul’s Hospital | Providence Health Care | Lower Mainland Pharmacy Services CSHP-BC Clinical Symposium Learning Objectives • By the end of this 45-minute session, the audience should be able to: – State the common causes of valvular heart disease – List the complications of valvular heart disease – Describe the hemodynamic consequences of valvular heart disease – Describe the indication for and alternatives of pharmacotherapy in valvular heart disease, specifically in aortic stenosis, aortic regurgitation, mitral stenosis and mitral regurgitation – Describe the principles of pharmacotherapy after valve surgery – State the antithrombotic recommendations for various prosthetic valve replacements, including transcatheter valve implantation – Explain when ASA should or should not be added to the vitamin K antagonist in patients with prosthetic heart valves 18 September 2014 Outline • • • • • • • • Valve anatomy and physiology Diagnosis of VHD Complications of VHD Specific valve pathologies – Aortic stenosis and regurgitation – Mitral stenosis and regurgitation Open heart surgery Prosthetic heart valves Anticoagulation Controversies Introduction Guidelines and Resources • 2014 AHA/ACC Valvular Heart Disease Guidelines – Full: Circulation 2014;129(23):e521-643 – Executive Summary: Circulation. 2014;129(23):2440-92 • 2012 ESC Valvular Heart Disease Guidelines – Eur Heart J 2012;33(19):2451-96 • 2012 CHEST Guidelines for Valvular Heart Disease – CHEST 2012;141(2)(Suppl):e576S–e600S • 2006 AHA/ACC Valvular Heart Disease Guidelines – J Am Coll Cardiol 2006;48(3);e1-148 • Canadian Cardiovascular Pharmacist Network (CCPN) Antithrombotic Guidelines Pocket Reference 2008 – http://ccpn.ca/docs/AntithromboticThrombolyticTxPocketcard.pdf Figure: Number waiting for and completed open heart surgeries in BC (CABG, valve, other) • Valvular heart disease (VHD) affects > 100 million people worldwide • In Canada, VHD is less common than other cardiac conditions like CAD, HF, HTN • The burden of VHD is increasing – High incidence of rheumatic heart disease in developing countries – ↑ burden of degenerative valve disease in developed countries – Patients with valve disease are living longer and diagnosis is often made at an older age • ↑ frequency of comorbidity, ↑ risk of intervention – ↑ in previously operated patients who require re-operation Eur Heart J 2003;24:1231–1243 | Lancet 2006;368:1005–1011 Lancet 2009; 374:565-76 | Cardiac Services BC Annual Report 2011 Cardiac Services BC Annual Report 2011 Heart Valve Anatomy Valve Physiology • Right Heart – Tricuspid Valve – Pulmonary Valve • Left Heart – Mitral Valve – Aortic Valve http://www.ssmhealth.com/heart/PublishingImages/heart.jpg http://healthtopics.hcf.com.au/images/hcf/gifs/heart-valve-replacement.gif Valve Function Valve Pathology • Valve does not open – Stenosis • Valve does not close – Insufficiency • Valve leaflets do not close together – Regurgitation • Backward blood flow http://www.drugs.com/health-guide/images/205521.jpg Diagnosis and Types of VHD • Identification – On physical exam (e.g. heart murmur) – Symptoms (eg syncope, CP, SOB, ↓ exercise tolerance, HF) • May not be recognized by the patient due to progressive nature valve disease – Incidental finding (e.g. chest imaging) • Diagnosis – Echo (TTE or TEE) • Tricuspid valve regurgitation or stenosis • Pulmonary valve regurgitation or stenosis • Mitral regurgitation or stenosis • Aortic regurgitation or stenosis – Other: CXR, ECG, coronary angiogram, cardiac CT, cardiac MRI Circulation. 2014 Jun 10;129(23):e521-643 http://www.drugs.com/health-guide/images/205522.jpg Valve Disease Classification • Classification of valve disease severity: – Mild, moderate, severe • Based on: – Symptoms – Echocardiography findings • Valve anatomy • Gradients: Pressure difference across the valve • Valve area – More applicable in valve stenosis – Measured when the valve is open – Hemodynamic complications Circulation. 2014 Jun 10;129(23):e521-643 Complications of Valvular Heart Disease • • • • • • E.g. Survival in Aortic Stenosis Symptoms – Due to ↓ in cardiac output HF – With preserved EF • ↓ in cardiac output, but LV function and size remains normal – With ↓ EF and/or ↓ LV function • Will occur over time if the VHD remains untreated AF – Especially with mitral stenosis Pulmonary hypertension Stroke Mortality http://www.allinahealth.org/ahs/helpingyourheart.nsf/page/heart.png/$FILE/heart.png Management Strategies • Monitoring – Asymptomatic valve disease – Echo every 1-5 years • Medical management – For those awaiting surgical intervention – Valve not amenable to surgical intervention – Decreased life expectancy • Valve repair or replacement – Symptomatic or severe valve disease – Reasonable life expectancy and quality of life Specific Valve Pathologies • • • • Aortic Stenosis (AS) Aortic Regurgitation (AR) Mitral Stenosis (MS) Mitral Regurgitation (MR) Circulation. 2014 Jun 10;129(23):e521-643 Aortic Valve Aortic Stenosis http://www.mountsinai.org/static_files/MSMC/Images/microsite/Interventional%20Cardiology%20Cath%20Lab/Enlarged%20Image%20Gallery/Aortic-Stenosis-lg.jpg https://myhealth.alberta.ca/health/_layouts/healthwise/media/medical/hw/h9991304_001.jpg https://science.nichd.nih.gov/confluence/download/thumbnails/35422393/aorticvalve2.jpg?version=1&modificationDate=1253127771000&api=v2 http://www.allinahealth.org/ahs/helpingyourheart.nsf/page/aortic_valve.png/$FILE/aortic_valve.png Aortic Stenosis • • AS and LV Remodeling Most common type of VHD Etiology – Calcified disease of normal leaflet (80%) • 2-7% in those > 65y; generally present when 70-80y • Inflammatory condition similar to atherosclerosis – Risk factors: older age, male, smoking, HTN, diabetes, LDL, lipoprotein and CRP – Calcified disease of bileaflet valve • Present in 2% of population; present in 10% of 1st degree relatives • More common in men; presents earlier (ie. 50-60y) – Rheumatic: rare (except in India) AS is a chronic, progressive condition with a long latency period – Aortic sclerosis: leaflet thickening without obstruction (5% progress to AS) – Mortality 15-50% over 5 years once symptomatic • Eur Heart J. 2012 Oct;33(19):2451-96 Circulation. 2014 Jun 10;129(23):e521-643 http://www.marvistavet.com/assets/images/aortic_stenosis.gif Aortic Stenosis Medical management • • • • Aortic Regurgitation Aortic valve replacement (AVR) is only definite therapy for AS – Transcatheter aortic valve implantation (TAVI) may be considered for those who are poor surgical candidates No medical management improves survival in AS Prevention and asymptomatic AS – Treat HTN • HTN is associated with 56% increase in ischemic events and 2x increase in mortality • No studies addressing specific antihypertensives • In theory, ACEI or any afterload reducing agent should be beneficial (reduce LV fibrosis) – Statins have no benefit on the progression of AS Awaiting surgical intervention – Use vasodilators with caution (e.g. nitrates) • Nitrates reduce preload http://www.heart-valve-surgery.com/Images/aortic-valve-regurgitation-image.jpg Eur Heart J. 2012 Oct;33(19):2451-96 Circulation. 2014 Jun 10;129(23):e521-643 Aortic Regurgitation Medical Management Aortic Regurgitation • Having bicuspid AV ↑ risk of AR, aortic dilatation and dissection • 2 types: chronic and acute • Etiology – Primary disease of aortic valve or aortic root • Calcified disease, annuloaortic ectasia (root dilation due to HTN or aging), Marfan’s syndrome, aortic dissection, collagen vascular disease, syphilis – Rheumatic disease – Infective endocarditis (IE) – Post-TAVI or valvuloplasty • Once symptoms present, mortality is 10-20% per year without surgery Eur Heart J. 2012 Oct;33(19):2451-96 Circulation. 2014 Jun 10;129(23):e521-643 • • • • AR is a state of increased afterload, hence use afterload reducing agents Chronic AR – Treat HTN with preferably an ACEI/ARB Acute AR – Early surgery is superior to medical management – May result in acute pulmonary edema and reduced cardiac output – Use vasodilators and inotropes for short-term improvement of symptoms – Avoid BB • Blocks compensatory tachycardia and will reduce BP even further Severe AR (not amenable to surgical intervention) – ACEI/ARB and BB are reasonable if ↓ EF • ACEI / ARB have been shown to reduce need for AVR, hospitalization for HF and death from HF Circulation. 2014 Jun 10;129(23):e521-643 Mitral Valve Mitral Stenosis http://www.heart-valve-surgery.com/Images/mitral-valve-annulus.jpg | http://circ.ahajournals.org/content/120/13/1287/F1.large.jpg http://www.merckmanuals.com/media/home/figures/CVS_stenosis_regurgitation_valves_b.gif Mitral Stenosis Mitral Stenosis • Etiology – Rheumatic heart disease (most common; in women) – Calcification • Survival in asymptomatic patients is generally up to 10 years • Progression is highly variable with sudden deterioration – Precipitated by pregnancy, AF or embolism • LV function is generally normal • Most common complication: AF • Mainstay of therapy is valve replacement – High operative mortality 3-10% http://dokterpenulis.files.wordpress.com/2008/03/mitral-stenosis-lg.jpg Eur Heart J. 2012 Oct;33(19):2451-96 Circulation. 2014 Jun 10;129(23):e521-643 Mitral Stenosis Medical Management • Diuretics or nitrates to relieve symptoms • 40% of patients with MS will develop AF – Anticoagulation regardless of CHADS2 score • Mitral stenosis = “Valvular” AF – HR control • Patients with MS are at high risk of atrial arrhythmias • In patients with NSR – HR control if symptomatic with exercise • Secondary prevention of Rheumatic fever – For at least 10y or until patient is 40y (which ever is longer) – Pen G, Pen V, Sulfadiazine, Macrolide Circulation. 2014 Jun 10;129(23):e521-643 Mitral Regurgitation • • • • Primary MR Secondary MR Acute MR Chronic MR • 2nd most common type of VHD requiring surgery Eur Heart J. 2012 Oct;33(19):2451-96 http://mvpresource.com/wp-content/uploads/2014/03/What-Is-Mitral-Regurgitation.png Mitral Regurgitation Primary MR • • • • Disruption to various parts of the mitral apparatus Etiology – Rheumatic (↓ incidence) – Degenerative (myxomatous degeneration) or collagen vascular disease – IE – Trauma or radiation (e.g. chordae rupture) Acute or chronic – Acute: Leaflet perforation, chordae rupture, papillary muscle dysfunction or rupture; may result in acute pulmonary edema • Poorly tolerated, poor prognosis – Chronic: may progress insidiously, causing LV dysfunction before symptoms High risk of mortality and morbidity – 14% CV death, 22% all-cause death; 33% cardiac event Mitral Regurgitation Primary MR • • Management strategy – Replacement – Repair • Lower peri-op mortality, improved survival, better preservation of post-op LV function, lower risk of long term morbidity Medical management – Reduce filling pressures with nitrates and diuretics – Nitroprusside for reducing pre-load and afterload (↓ regurgitant fraction) – Inotropes for hemodynamic support – Medical therapy for systolic dysfunction if not a valve surgery candidate and EF < 60% (BB, ACEI/ARB, aldosterone antagonists) – BB improve surgical outcomes, delays onset of LV dysfunction, reverse LV dysfunction – No evidence for ACEI in chronic MR without HF Eur Heart J. 2012 Oct;33(19):2451-96 Circulation. 2014 Jun 10;129(23):e521-643 Circulation. 2014 Jun 10;129(23):e521-643 | J Heart Valve Dis 1993;2:512-22. J Am Coll Cardiol. 2012;60:833-8. | J Am Coll Cardiol. 2002;40:149-54. Mitral Regurgitation Secondary (Functional) MR • • • • • • • Mitral Regurgitation Secondary (Functional) MR Also known as: ischemic MR MV leaflets and chordae are structurally normal MR caused by LV dysfunction (secondary to CAD, MI, cardiomyopathy) Generally poor prognosis compared to primary MR – Not improved by revascularization Myocardial viability imaging should be performed pre-surgery Operative mortality is higher – Presence of comorbidities – Repair yields better outcomes than replacement • High risk of MR recurrence Medical Management – Treat LV dysfunction (ACEI/ARB, BB, aldosterone antagonists) – Treat cause of LV dysfunction Circulation. 2014 Jun 10;129(23):e521-643 | J Heart Valve Dis 1993;2:512-22. J Am Coll Cardiol. 2012;60:833-8. | J Am Coll Cardiol. 2002;40:149-54. http://www.mardil.com/wp-content/uploads/2011/02/NormalAbnormalFinal3.png Open Heart Surgery History Basic Principles of Medical Management in VHD • Risk factor management – Treat HTN, dyslipidemia, diabetes • Treat the altered hemodynamics in each specific valve pathology • Treat LV dysfunction if present – Diuresis, ACEI/ARB, BB, aldosterone blockers • Rheumatic fever prophylaxis – Prompt treatment of streptococcal pharyngitis • Infective endocarditis prophylaxis (for those with prosthetic heart valves only) – Oral health is key • Vaccinations – Influenza and pneumococcal • Exercise – Lack of studies in VHD – May suggest regular aerobic exercise for select VHD patients Circulation. 2014 Jun 10;129(23):e521-643 1895 1925 1960 1990s 2005 2013 First Open Heart Surgery First Valve Surgery First prosthetic heart valve: StarrEdwards cagedball First offpump open heart surgeries First transapical valve in Canada First “tiara device” mitral valve Open Heart Surgery Introduction • Valve surgery is the mainstay of therapy for severe VHD – 30% of VHD patients receive a prosthetic heart valve • Over the last 50 years, there have been major advances in surgical techniques and post-operative care for the VHD patient • Generally, the risk of mortality of severe VHD greatly outweighs the risk of perioperative mortality • In BC, 30-day adjusted mortality remains low compared to society of thoracic surgeon (STS) reports – Valve surgery: 2-3% (STS 3.4%) – CABG + Valve surgery: 4-6% (STS 6.8%) Open Heart Surgery Operation • • • • • • • Sedation Mechanical Ventilation Sternotomy or thoracotomy – Tranexamic acid Cardiopulmonary bypass machine – Heparinized circuit • Protamine to reverse – Fluids and blood products PRN – Vasopressors (no inotropes) Cardioplegia – Potassium – Hypothermia Pre-, intra-, and post-op transesophageal echo (TEE) Chest tubes Eur Heart J 2003;24:1231–1243. | Lancet 2006;368:1005–1011 Lancet 2009; 374:565-76. | Cardiac Services BC Annual Report 2011 http://mehmanesh.com/wp-content/uploads/2013/05/open-heart.png Post Open Heart Surgery Medical Management Post-op Care Inotropes and vasopressors Diuresis AF prophylaxis Stress ulcer prophylaxis DVT prophylaxis Post-op complications management – Delirium – Arrhythmias or heart block – AKI – Nausea and vomiting – Bleeding – Hyperglycemia – Skin and soft tissue infection • Home meds restarted • • • • • • • • • • • • On Discharge Diuresis Change in antithrombotics Change in BP meds AF – Treatment – Prophylaxis Change in diabetes meds Stress ulcer prophylaxis Bioprosthetic (1970) Prosthetic Heart Valves Types Bioprosthetic Brands: ATS Medical, Carpentier-Edwards, Edwards, Medtronic, St. Jude Medical, Sorin Mechanical Brands: ATS Medical, Edwards, Medtronic, On-X, Sorin, St Jude Medical. Transcatheter - Transfemoral (AV) - Transapical (AV, MV) Brands: Edwards Sapien, CoreValve, Sapien XT THV Selection Criteria Homograft Xenograft - Porcine valve - Bovine pericardium ~10-20 year life span Older patient Not ideal to be on warfarin More physiological hemodynamics Caged-ball Tilting disc single leaflet Bileaflet Indefinite life span Younger patient Patient has another indication for warfarin Bovine pericardium Porcine pericardium Recommended in those who are high risk surgical candidates Expected life expectancy > 12 months post-surgery Eur Heart J. 2012 Oct;33(19):2451-96 | Circulation 1994;89:635-41 | Lancet 2009;374:565-76. Transcatheter Transcatheter Valves Mechanical Caged-ball (1960) Tilting disc (1969) Bileaflet (1977) Lancet 2009;372:565-76 | http://img.medscape.com/pi/emed/ckb/clinical_procedures/79926-1889862-1971097-1972129.jpg https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcR4bfMO0p97BSFFz-035ceLnzvqCuzPQmpC7T6w4YUT6jdsimAc Anticoagulation in Prosthetic Valves Goals of Therapy Therapeutic Alternatives • ASA • Prevent thrombosis – valve thrombosis (<2-4% per year) – major embolism (<4-8% per year) – total embolism (<9-18% per year) • Prevent thromboembolic stroke • Minimize bleeding – <1 to 2% yearly • Prevent mortality – ↓ major embolism by 40% – Total bleeding < 1% per year • Warfarin – ↓ major embolism by 75% – Total bleeding 2% per year • ASA + Warfarin – ↓ major embolism by > 75% – Total bleeding ~5% per year Circulation 1994;89:635-41 Eur Heart J. 2012 Oct;33(19):2451-96 Circulation 1994;89:635-41 Approach to Anticoagulation in Prosthetic Heart Valves • Risk of thrombogenicity determines choice of antithrombotic therapy – Location of valve • Mitral (2x) > Aortic – Type of valve • Mechanical (m) > Tissue (t) – Mechanical: caged-ball (5x) > tilting disc > bileaflet • Generation of valve – Timing of valve replacement / repair • Risk of thrombosis highest in first 3 months – Presence of additional thromboembolism risk factors J Am Coll Cardiol. 1995;25(5):1111-19| CHEST 2001; 119:220S-227S Circulation 1994;89:635-41 Choice of Antithrombotic Risk of Thrombosis Location & Type + RF? High ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ Lower MVR(m) or AVR(m) – Yes AF Enlarged left atria (>4.5-5cm in diameter) Reduced EF Hypercoagulable state Hx thromboembolism Atherosclerotic vascular disease – Cerebrovascular disease – Coronary artery disease – Peripheral arterial disease Duration Indefinite VKA to INR 3 + ASA caged ball or tilting disc - AVR(m) – Yes VKA to INR 3 + ASA Indefinite Indefinite bileaflet - VKA to INR 2.5 + ASA Indefinite MVR(t) or MV Repair Yes VKA to INR 2.5 + ASA VKA x > 3 mos, ASA indefinitely - VKA to INR 2.5 + ASA VKA x 3 mos, ASA indefinitely MV Repair or AVR(t) Yes VKA to INR 2.5 + ASA VKA x > 3 mos, ASA indefinitely - (VKA to INR 2.5 x 3-6 mos) ASA alone ASA indefinitely Eur Heart J. 2012 Oct;33(19):2451-96 | Circulation. 2014 Jun 10;129(23):e521-643 | CHEST 2012; 141(2)(Suppl):e576S–e600S Additional Risk Factors (RF) for Thrombosis • • • • • • Antithrombotic Recommendation Adding ASA to VKA Evidence for Adding ASA? 2003 Cochrane review of 11 RCTs (N=2428) in prosthetic valve patients found that adding ASA to OAC vs OAC alone: – ↓ mortality (RR 0.58, 95% CI 0.4-0.86) – ↓ thromboembolism (RR 0.42, 95% CI 0.21-0.81) – ↑ bleeding (RR 1.44, 95% CI 1-2.08) • Adding low dose ASA (<100mg) did not ↑ bleeding in this population • • • • • Add ASA Additional risk factors for thrombosis: – AF – Hypercoagulable state (e.g. thrombophilias) – Low EF – Vascular disease (e.g. CAD) – Hx embolism (e.g. VTE) Do not Add ASA Elderly (>80 years) Hx recent or severe bleeding (e.g. GIB) Other risk factors for bleeding – Abnormal renal or liver function – Other medications that ↑ bleeding risk CHEST 2012; 141(2)(Suppl):e576S–e600S NEJM 1993; 329:524-29 | J Am Coll Cardiol 2000;35:739-46 | CDSR 2003;4:CD003464 Anticoagulation in AVR(t) without additional thromboembolic risk factors • • • 2014 AHA guidelines recommend VKA x 3-6 months then ASA – 2008 AHA, 2012 ESC, 2012 CHEST: ASA alone – 2012 ESC: VKA x 3 months then ASA Aramendi et al. 2005 – P, R, OL, N=191 with bioprosthetic valves (94% AVR(t)) – triflusal 600mg daily vs. acenocoumarol (INR 2-3) x 3 mos – Outcome: Thromboembolism, hemorrhage, valve-related death at 180d = NSS Merie et al. 2012 – Retrospective cohort (Danish Registry), N=4075 AVR(t)+CABG, no previous indication for warfarin, no POAF – ASA, VKA, ASA + VKA, no ASA or VKA x 6.6y • Analyses done on VKA+ASA vs. ASA or No antithrombotic (N=2278+916 vs. N=181+700) • VKA x 30-89d, 90-179d, 180-364d, 365-729d, 730d – Outcomes: ↓stroke, ↓ thromboembolism, ↓ bleeding, ↓ CV death J Am Coll Cardiol. 1995;25(5):1111-19 | Eur J Cardiothorac Surg 2005;27(5):854-60 JAMA. 2012;308(20):2118-25 JAMA. 2012;308(20):2118-25 Anticoagulation in Mitral Valve Repair Merie et al. 2012 • Bottom line: Use low-dose ASA alone in AVR(t) with no additional risk factors for thrombosis • There is controversy about the optimal antithrombotic in mitral valve repair – ASA + Warfarin x 3 months, then ASA alone – Warfarin x 3 months, then ASA – ASA • Observational studies demonstrate that risk of thromboembolism and bleeding are both low – Thromboembolism 0.4-3% per patient year – Bleeding 0.3-0.8% per year – Confounded by 1/3 of patients developing AF during first 3 months Interact Cardiovasc Thorac Surg 2006;5:761-6. JAMA. 2012;308(20):2118-25 Anticoagulation in Mitral Valve Repair Antithrombotics in Transcatheter Valves • • • http://www.mitralvalverepair.org/images/surgery/figure8.jpg http://www.thechristhospital.com/upload/images/Departments/Heart%20and%20Vascular/MV_with_System_high%20res.jpg St. Paul’s Hospital first pioneered the transfemoral and transapical approaches for TAVI in 2005 – > 200 TAVIs have been completed since Major complications: stroke, bleeding, hypotension, conduction disturbances, AF, AKI, vascular injury, anemia, paravalvular leak – Stroke rates and bleeding rates > 15% at 30d, which are independent risk factors for mortality Antithrombotic alternatives – ASA 50-100mg daily + clopidogrel 75mg daily x 3-6 months then ASA indefinitely (guideline recommended) • 2 RCTs and 1 prospective observational trial – ASA alone – ASA + warfarin – Clopidogrel + warfarin – Warfarin alone Cardiology Clinics 2013;31:607-18| JACC Cardiovasc Interv 2014;7:152-3 | Catheter Cardiovasc Interv 2011;78:457-67 Eurointervention 2010;5:666-72 | CHEST 2012; 141(2)(Suppl):e576S–e600S Investigational Transcatheter Valves Bridging of Anticoagulation • • • • • Bridging ↑ risk of bleeding; unknown whether the ↑ risk of bleeding is off-set by the benefits of ↓ thrombosis Bridging is not required for procedures that are low risk of bleeding (e.g. dental extractions); warfarin should be continued 2012 CHEST recommends bridging for risk of thrombosis 5 to > 10% yearly – Any MVR(m), bileaflet AVR(m) with AF, cage-ball or tilting disc AVR(m), any AVR and recent CVA (<6 months), AF with Rheumatic valve disease Pre-op: stop warfarin x 3-5 days, LMWH bridging Post-op management varies – Bridging depends on the risk of bleeding from the surgery • Heterogeneous definitions exist depending on type of surgery – Post open heart surgery (OHS) • Generally risk of bleeding > thrombosis post-OHS • Do not bridge with LMWH; low target IV heparin protocol to start POD 1-3 CHEST 2012;141(2)(Suppl):e326S-e350s J Am Coll Cardiol 2012;60:483-92 Novel Oral Anticoagulants (NOACs) in Prosthetic Heart Valves • Studies with NOACs in AF excluded patients with valvular heart disease (e.g. mitral stenosis) and prosthetic heart valves • Dabigatran is contraindicated in those with mechanical valves – RE-ALIGN Trial prematurely terminated • Phase II, Dabi in mechanical valves • Unknown if Factor Xa Inhibitors provide adequate anticoagulation – Ongoing: Rivaroxaban in mechanical AVR (NCT02128841) • Lack of evidence in bioprosthetic valves or valve repairs – Possible NOAC use in AF and AVR(t) • AVR(t) is the least thrombogenic prosthetic valve – Low dose ASA daily • Select surgeons have been recommending ASA + warfarin x 3 months then resume NOAC Prosthetic Heart Valves Limitations of the Literature • Small sample size, non-randomized trials – Observational trials or case series • Risk of thrombosis comes from studies with 1st generation valves – For newer valves, company may conduct biased in-house studies and make recommendations • Heterogeneous valve types (AV and MV) studied with different baseline thrombosis or bleeding risks • Target INRs, frequency of INR checks, TTR infrequently reported • Other risks of thrombosis or bleeding poorly document or uncontrolled for • Advances in surgical techniques and post-surgical care will affect thrombosis and bleeding outcomes Eur J Cardiothorac Surg 2005;27(5): 854-860. General Pharmacotherapeutic Approach to the VHD Patient • • Pre-surgical intervention – Mild to moderate (watch and wait) • Risk factor management • Educate patient on important signs and symptoms – Moderate to severe (surgery is imminent) • Support hemodynamics with pharmacotherapy specific to the pathophysiology • Stop anticoagulation in preparation for surgery Post-surgical intervention – Re-evaluate need for pre-op medical management medications – Treat LV dysfunction if present – Assess need for anticoagulation and duration – Risk factor management – Minimize risk for infective endocarditis • Recommend routine dental care • Antibiotic prophylaxis for dental procedures in those with prosthetic heart valves Summary • Valvular heart disease encompasses many valvular pathologies • Making pharmacotherapeutic decisions in VHD is complex • Pharmacotherapy has a distinct role in the overall management of VHD patients • Choice of antithrombotic to balance the risks of thrombosis and bleeding takes into account a variety of factors • Novel surgical techniques (e.g. TAVI) will pose new therapeutic challenges • The pharmacist can play an important role in optimizing pharmacotherapy wherever the patient may be in their valvular heart disease journey