Effects of Paroxetine on Mortality and Hospital Admissions in Heart Failure Patients

Transcription

1 Effects of Paroxetine on Mortality and Hospital Admissions in Heart Failure Patients MARIE ANN NGAN, PHARM.D. OKLAHOMA CITY VA HEALTH CARE SYSTEMS PGY1 PHARMACY RESIDENT APRIL 8, 2016 Disclosure Statement I have nothing to disclose

2 Objectives Explain the effects of cardiovascular disease in the world and America Describe the purposed mechanism of action for paroxetine use in heart failure patients Pre-Test How many people die from heart disease per year? 250, , , ,000

3 Pre-Test Fluoxetine has the same purposed mechanism to improve heart failure as paroxetine. True False Pre-Test Dysregulation to the G-protein coupled receptor (GPCR) in the heart can result in: Increase heart rate Decreased heart rate Decrease cardiac output B and C None of the above

4 Cardiovascular Disease Background Leading cause of death globally Accounts for 17.3 million deaths per year Projected to increase to 23.6 million by 2030 Number 1 cause of death in the United States 375,000 people die due to heart disease each year Indirect and direct cost of >$320.1 billion Cardiovascular Disease and Depression Depression occurs in 20% of patients who have heart failure As severity of heart failure worsens, the rate of depression increases Studies have shown direct relationship between depression and worsening or increasing of: Outcomes Quality of life Hospitalizations Mortality Common therapy for depression includes selective serotonin reuptake inhibitors ie: Paroxetine

5 MOA of Paroxetine in Cardiac Dysfunction and Remodeling G protein coupled receptors (GPCR) and G protein coupled receptor kinase 2 (GRK2) is upregulated in failing human heart Stimulate B-adrenergic receptors GPCR and GRK2 = Cell Death Specifically, paroxetine selectively inhibits GRK2 over other GRKs, which may decrease cell death Schumacher SM, et al. Paroxetine Mediated GRK2 inhibitions Produced ~30% absolute increase in LVEF Produced 20% absolute increase in fractional shortening 6 weeks after a myocardial infarction MOA of GPCR and GRK2

6 Effect of Paroxetine in Heart Failure Patient at OKCVAHCS Purpose Retrospective chart review from July 1 st, July 1 st, 2015 Groups Heart failure patient on fluoxetine (control) Heart failure patients on paroxetine (treatment) Objectives Primary: Identify the prevalence of heart failure mortality and/or re-admissions/er visits within 1 year of having 2 consecutive fills of studied drug Secondary: Identify the difference in blood pressure and heart rate between paroxetine and fluoxetine after at least 60 days of initiation of therapy. Effect of Paroxetine in Heart Failure Patient at OKCVAHCS Drug 2,098 patients Heart Failure (HF) 2,098 patients Fluoxetine 1,416 patients Paroxetine 682 patients Drug + HF 301 patients Drug + HF 254 patients Excluded based on age (47 patients) Excluded due to not having 2 consecutive fills (93 patients) Drug + HF 161 patients Fluoxetine 107 patients Paroxetine 54 patients

7 Post-Test How many people die from heart disease per year? 250, , , ,000 Post-Test Fluoxetine has the same purposed mechanism to improve heart failure as paroxetine. True False

8 Post-Test Dysregulation to the G-protein coupled receptor (GPCR) in the heart can result in: Increase heart rate Decreased heart rate Decrease cardiac output B and C None of the above Conclusion Cardiovascular disease affects people not just in America but world wide Leading cause of death worldwide Number 1 cause of death in the United States Proposed MOA for paroxetine is inhibition of GRK2 Fluoxetine does not inhibit GRK2 Purpose of this study may result in drug development that targets the inhibition of GRK2 for heart failure or post myocardial infarction patients in the future

9 References 1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després J-P, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics 2015 update: a report from the American Heart Association [published online ahead of print December 17, 2014]. Circulation. doi: /CIR Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure: a meta-analytic review of prevalence, intervention effects, and association with clinical outcomes. J Am Coll Cardiol. 2006;48(8): Fulop G, Strain JJ, Stettin G. Congestive heart failure and depression in older adults: clinical course and health services use 6 months after hospitalization. Pyschosomatics 2003;44: Carls RA. The association between disease severity, function status, depression, and daily quality of life in congestive heart failure patients. Qual Life Res 2004;13: Jiang W, Alexander J, Christopher E, et al. Relationship of depression in increased risk of mortality and rehospitalization inpatients with congestive heart failure. Arch Intern Med 2001;161: de Denus S, Spinler SA, Jessup M, Kao A. History of depression as a predictor of adverse outcomes in patients hospitalized for decompensated heart failure. Pharmacotherapy 2004;24: Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sagman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB. Decrease catecholamine sensitivity and B-adrenergic-receptor density in failing human heart. N Engl J Med 1982;307: Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system in heart failure: pathophysiology and therapy. Circ Res 2013;113: Claing A, Laporte SA, Caron MG, Lefkowitz RJ. Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and B-arrestin proteins. Prg Neurobiol 2002;66: Rockman HA, Koch WJ, Lefkowitz RJ. Sevan-transmembrane-spanning receptors and heart function. Nature 2002;415: Schumacher SM, Gao E, Zhu W, Chen X, Chuprun K, Feldman AM, Tesmer JJG, Koch WJ. Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction. Science Translation Medicine 2015; Questions? marie.ngan@va.gov Phone: