With My Heart, Can or Should I Take Erectile Dysfunction Drugs?
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1 With My Heart, Can or Should I Take Erectile Dysfunction Drugs? Timothy R. Malinowski MD, FACC UMG Carolina Cardiology Consultants Greenville Health System
2 Definition of Erectile Dysfunction 1992 NIH Consensus Development Conference on Impotence American Urologic Association, The Management of Erectile Dysfunction, June 2007
3 Incidence of ED in the U.S. Massachusetts Male Aging Study: Overall prevalence 52% ED Increases with age: 40% at age 40 70% at age 70 Complete ED: 5% at age 40 15% at age 70
4 Incidence of ED with CV Disease 46% of men with CAD have ED CVD (atherosclerosis, HTN, HLP, stroke) is a risk factor for later ED
5 ED Predicts CV Disease Risk for CV event: 2.4% per year with ED 1.5% without ED CVD and ED have common etiology Endothelial dysfunction and atherosclerosis Sexual activity = 3-4 METS Absolute risk of MI with sexual activity: 20 per million per hour in men with H/O MI
6 History of ED Drugs 1989: Sildenafil created by Peter Dunn and Albert Wood. Failed as treatment for HTN and Angina Changed focus to treating ED due to peculiar side effect 1996: Pfizer patents Sildenafil in U.S. 1998: FDA approves Viagra to treat ED
7 History of ED Drugs 1998: 40,000 prescriptions for Viagra in first few weeks after release. 12 million prescriptions in the first 2 years Newsweek: Hottest New Drug in History Washington Post: CIA Using Viagra to Gain Support in Afghanistan
8 This is you...
9 This is you on Viagra.
10 History of ED Drugs 2000: Dr. Sanjay Kaul reports at Annual Scientific Session of ACC 522 Deaths in pts taking Viagra in its first year 517 additional had MI or angina 2003: FDA approves Vardenafil (Levitra) and Tadalafil (Cialis) 2011: Pfizer s U.S. patent for Viagra extended until : FDA approves Avanafil (Stendra)
11 Pharmacology Drug Class: Phosphodiesterase 5 Inhibitors Sexual stimulation Endothelial release of nitric oxide Binds to guanilate cyclase receptors Increased c-gmp Smooth muscle relaxation, vasodilation Increased blood flow to penis: erection Inhibiting PDE5 enhances vasodilation / erection
12 Clinical Indications for PDE5 Inhibitors Erectile Dysfunction Efficacy: Sildenafil: 55-89% Tadalafil: 45-93% Vardenafil: 58-66% Pulmonary Hypertension
13 Potental PDE5 Inhibitor Use in CV Disease CHF Doxorubicin Cardiotoxicity Cardioprotection HAPE and HAPH Resistant Hypertension Raynaud s Phenomenon
14 PDE5 Inhibitors in CHF (J Am Coll Cardiol 2012;59:9 15) 2012 by the American College of Cardiology Foundation
15 PDE5 Inhibitors (Animal Studies) Prevention of Doxorubicin Toxicity Activation of mitochondrial antioxidative and antiapoptotic mechanisms, without loss of chemotherapeutic effect. Cardioprotection Given prior to coronary occlusion, decreases infarct size.
16 PDE5 Inhibitors in HAPE and HAPH Incidence: HAPE 4%, HAPH 5-18% (J Am Coll Cardiol 2012;59:9 15) 2012 by the American College of Cardiology Foundation
17 PDE5 Inhibitors in HAPE and HAPH Prevents recurrent HAPE Reduces pulmonary pressures and improves exercise parameters in HAPH
18 PDE5 Inhibitors in Resistant Hypertension
19 PDE5 Inhibitors in Resistant Hypertension 6 patients treated with Sildenafil and Isosorbide Mononitrate Up to 26/18 reduction in BP
20 PDE5 Inhibitors in Raynaud s Improves digital blood flow Improves symptoms Decreased frequency and severity of attacks Improves healing of digital ulcers
21 Safety and Side Effects PDE5 Inhibitors do not cause CV events Non-arteritic anterior ischemic optic neuropathy (NAION) Hearing Loss
22 PDE5 Inhibitors Contraindicated with Nitrates Nitrates increase c-gmp in vascular smooth muscle PDE5I s prolong action of c-gmp Causes severe, prolonged decrease in systemic BP Sildenafil + ISMN: BP drops 52/29 Sildenafil +SL NTG: BP drops 36/21
23 American College of Cardiology Recommendations Avoid PDE5 Inhibitors with: Active Coronary Ischemia Heart Failure with low BP or low volume status Complicated multi-drug anithypertensive regimens Taking CYP3A4 blockers (prolong PDE5I duration)
24 References Montague, et al. American Urological Assoc. The Management of Erectile Dysfunction: An Update June Feldman HA, et al. J. Urol, 1994; 151: Nascimento, et al. Clinics. 2013: 68(11): Lakin and Wood, Cleve Clin Online, November Thompson, et al. JAMA 2005; 294(23): Jackson, et al, J Sex Med, 3: 28, Muller et al, Am J Cardiol, 86: 14F, CNN.com, The Little Blue Pill That Could UpToDate 2016 Schwartz et al, JACC Vol 59, No 1, 2012.
25
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