My Heart Will Go on: ANTICOAGULATION NO LONGER STOPS AT VALVULAR HEART DISEASE
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1 Disclosures My Heart Will Go on: ANTICOAGULATION NO LONGER STOPS AT VALVULAR HEART DISEASE Nicholas Boemio, PharmD- No potential or actual conflicts of interest to disclose Kim L. Daley, PharmD, BCGP, CDP- No potential or actual conflicts of interest to disclose Nicholas Boemio, PharmD PGY-1 Pharmacy Practice Resident VA Connecticut Healthcare System Kim L. Daley, PharmD, BCGP, CDP Clinical Pharmacy Specialist VA Connecticut Healthcare System Objectives: Disclaimer: 1. Define risk factors, prevalence, and diagnostic criteria of valvular heart disease (VHD) 2. Describe the 2017 AHA/ACC Focused Update s recommendations regarding anticoagulation in patients with atrial fibrillation and the evidence used to support them Please note that guidance related to the management of valvular heart disease is only fully updated every 6 years with focused updates created on an as needed basis. Recommendations discussed during this presentation may become outdated in the future as new agents and clinical data becomes available. ONE MINUTE PAPER!!! Background THE TIP OF THE ICEBERG 1
2 NIH. What causes heart valve disease. Available at: Accessed October 21, Iung B, Vahanian A. Epidemiology of acquired valvular heart disease. Can J Cardiol Sep;30: NIH. What causes heart valve disease. Available at: Accessed October 21, Iung B, Vahanian A. Epidemiology of acquired valvular heart disease. Can J Cardiol Sep;30: Iung B, Vahanian A. Epidemiology of acquired valvular heart disease. Can J Cardiol Sep;30: NIH. How is heart valve disease diagnosed. Available at: Accessed October 21, Meet the Cast: Prevalence: Mitral Stenosis (MS): typically due to rheumatic disease, but in less severe cases due to progressive calcification Aortic Stenosis (AS): slow progression of aortic sclerosis which leads to valve obstruction, remodeling, and further calcification Mitral Regurgitation (MR): volume overload of the left ventricle leads to valve prolapse and further pathological valve remodeling leaky valve Aortic Regurgitation (AR): histological abnormalities and volume overload in the aorta leads to valve prolapse and further pathological remodeling leaky valve Overall Age-adjusted moderate or severe valvular disease: 2.5% Increasing prevalence with age due to degenerative valve disease Healio. Heart murmurs topic review. Available at: Accessed October 21, Risk Factors: Knowledge Check Increasing age (greatest risk over 75 years) History of infective endocarditis, rheumatic fever, myocardial infarction, heart failure, or other valve disease Hyperlipidemia Hypertension Family history of early heart disease Smoking Congenital heart disease or histological abnormalities Diabetes Obesity Lack of physical activity CD is a 49 year old female with PMH significant for HTN, HLD, DM, MI in 2013, migraines (about 2 per month), and GERD who presents to her PCP for routine follow-up. Since her MI in 2013, CD works out 4 times per week to help maintain a healthy weight (BMI=21.2) and lifestyle. She denies any tobacco or alcohol use. Family history is non-significant. CD s most recent echocardiogram from June 2015 was normal. Which of the following is NOT one of CD s risk factors developing valvular heart disease in the future? A. Previous MI in 2013 C. BMI of 21.2 B. Diabetes Mellitus D. Hypertension Healio. Heart murmurs topic review. Available at: Accessed October 21, Mitral Stenosis (MS) Diagnosis HOW DO WE TELL THEM APART? Relatively unremarkable pulses Opening snap followed by decrescendo-crescendo murmur Left atrial enlargement Extended P-wave duration; atrial fibrillation Hockey stick deformity 2
3 NIH. How is heart valve disease diagnosed. Available at: Accessed October 21, NIH. How is heart valve disease diagnosed. Available at: Accessed October 21, NIH. How is heart valve disease diagnosed. Available at: Accessed October 21, Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol Jul 11;70: Aortic Stenosis (AS) Mitral Regurgitation (MR) Arterial pulse is less pronounced on carotid pulse Crescendo-decrescendo systolic murmur Relatively normal with cardiomegaly in late stage AS Left ventricular hypertrophy (85%) Focal areas of valve thickening, left ventricular hypertrophy High-pitched blowing holosystolic murmur Cardiomegaly Left atrial enlargement; atrial fibrillation Turbulent flow at the mitral valve Aortic Regurgitation (AR) Knowledge Check Widened pulse pressure due to elevated SBP and depressed DBP Diastolic decrescendo murmur; shortens with severity Some pulmonary congestion Normal early with prominent Q waves later Turbulent flow at the aortic valve On physical exam, CD presents with a new crescendo-decrescendo systolic murmur and a less pronounced carotid pulse. CD s PCP orders an echocardiogram which is significant for some aortic valve thickening and mild left ventricular hypertrophy. Based on CD s physical exam and echocardiogram findings, which valvular disease has she developed? A. Aortic stenosis C. Mitral regurgitation B. Mitral stenosis D. Aortic regurgitation Valvular Atrial Fibrillation THE JEWEL OF THE FOCUSED UPDATE 3
4 Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GY, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ Feb 10;356:j510. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GY, Larsen TB. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ Feb 10;356:j510. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Guidelines Recommendations: Evidence: Patients with RHEUMATIC MITRAL STENOSIS and atrial fibrillation SHOULD be anticoagulated with a VITAMIN K ANTAGONIST (VKA) (COR: I LOE: B-NR) Landmark DOAC trials explicitly excluded mitral stenosis: ARISTOTLE: Moderate to severe mitral stenosis RE-LY: Significant mitral valve stenosis; valve disease requiring intervention ROCKET-AF: hemodynamically significant mitral valve stenosis ENGAGE-AF-TIMI: moderate to severe mitral stenosis BUT WAIT. THERE S MORE THERE S MORE Retrospective claims data analysis: Population: Warfarin vs NOACs (apixaban, dabigatran, rivaroxaban) Patients with post-surgical or native valvular heart disease and atrial fibrillation Outcomes: Efficacy: Rate of stroke or systemic embolism Safety: Rate of major bleeding Results: Patients with AS/AR/MR: Statistically significant reduction in stroke/systemic embolism and major bleeding compared to warfarin Patients with MS: Stroke/Systemic Embolism: HR: p= 0.31 Major Bleeding: HR: p=0.40 Guideline Recommendations: Guideline Recommendations: Anticoagulation is indicated in patients with atrial fibrillation and a CHA 2 DS 2 -VASc score of 2 or more WITH native aortic valve disease, tricuspid valve disease or MR (COR I LOE: C-LD) BUT ARE OUR OPTIONS OPEN? It is REASONABLE to use a DIRECT ACTING ORAL ANTICOAGULANT (DOAC) as an alternative to a VKA in patients with atrial fibrillation, a CHA 2 DS 2 -VASc score greater than 2, AND native aortic valve disease, tricuspid valve disease, or MR. (COR: IIa LOE: C-LD) 4
5 Siontis KC, Yao X, Gersh BJ, Noseworthy PA. Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis. Circulation Feb 14;135: Siontis KC, Yao X, Gersh BJ, Noseworthy PA. Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis. Circulation Feb 14;135: Siontis KC, Yao X, Gersh BJ, Noseworthy PA. Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis. Circulation Feb 14;135: Evidence: A Closer Look: Post-hoc Meta-analysis: VHD Overall Results: Risk of stroke/systemic embolism: HR: No significant difference between VHD and Non-VHD No significant heterogeneity Risk of major bleeding: HR: No significant difference between VHD and Non-VHD No significant difference between DOAC and warfarin Significant heterogeneity A Closer Look: Knowledge Check During an EKG as part CD s aortic stenosis work-up, CD was found to have an irregularly-irregular heart rhythm consistent with atrial fibrillation. CD s PCP contacts your pharmacy for recommendations regarding anticoagulation due to her CHA 2 DS 2 -VASc Score of 4 and comorbid valvular disease. Given CD s newly diagnosed atrial fibrillation and aortic stenosis, which DOAC would you want to avoid due to increased risk of bleeding in patient s with valvular disease? A. Dabigatran C. Edoxaban B. Apixaban D. Rivaroxaban Summary: 1. Stick To Warfarin: For patients with rheumatic AND non-rheumatic mitral stenosis How you feel after becoming an expert on Valvular Heart Disease: 2. The Floodgates Are Open: DOACs can be considered in valvular atrial fibrillation USE CAUTION not all are created equal 3. Follow The Evidence: Increased risk of bleeding with rivaroxaban Decreased risk of stroke/systemic embolism with apixaban and dabigatran 5
6 References: 1. NIH. What causes heart valve disease. Available at: Accessed October 21, QUESTIONS? 2. Iung B, Vahanian A. Epidemiology of acquired valvular heart disease. Can J Cardiol Sep;30: Healio. Heart murmurs topic review. Available at: Accessed October 21, NIH. How is heart valve disease diagnosed. Available at: Accessed October 21, Maganti K, Rigolin VH, Sarano ME, Bonow RO. Valvular Heart Disease: Diagnosis and Management. Mayo Clinic Proceedings. 2010;85(5): Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O'Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol References: 7. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; ACC/AHA Task Force Members AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation Jun 10;129: Siontis KC, Yao X, Gersh BJ, Noseworthy PA. Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease Other Than Significant Mitral Stenosis and Mechanical Valves: A Meta-Analysis. Circulation Feb 14;135:
My Heart Will Go on: Disclosures 3/2/2018
My Heart Will Go on: ANTICOAGULATION NO LONGER STOPS AT VALVULAR HEART DISEASE Nicholas Boemio, PharmD PGY-1 Pharmacy Practice Resident VA Connecticut Healthcare System Kim L. Daley, PharmD, BCGP, CDP
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