1. Erectile Dysfunction and Cardiovascular Disease

2. ED and Cardiovascular Diseases

6. Malattie cardiovascolari e disfunzione erettile Alterazione vascolare Aterosclerosi diffusa, ostruzione al flusso ematico Produzione di EDRF Peptidi vasoattivi Sindrome dismetabolica Terapia farmacologica Psicologica

7. DiureticiFrequente Beta-bloccantiFrequente Ca- antagonisti VerapamilFrequente DiltiazemFrequente AmlodipinaFrequente ACE-InibitoriFrequente ATII antagonistiRaro Alfa-liticiPotenziamento erezione Malattie cardiovascolari e disfunzione erettile Effetto della terapia farmacologica

8. Study Design Run in 3 months Atenolol - know side effects Atenolol - do not know side effects Atenolol - do not know drug Sildenafil Placebo Sildenafil Placebo Sildenafil Placebo QOL Questionnaire Report of ED Silvestri et al. In Press Eur Heart J 2003

9. Beta-blockers and Report of ED P<0.05 P<0.01 Comparisons vs pts blinded on treatment drug Silvestri et al. In Press Eur Heart J 2003

10. Effect of Sildenafil Citrate and Placebo in Patients Reporting ED Silvestri et al. In Press Eur Heart J 2003

11. Incidence of Cardiovascular Disease in Patients Referred for ED Study Objective  Evaluate cardiovascular risk and incidence of cardiovascular disease in cardiac asymptomatic patients with ED Study esign  Indication of exercise ECG and eventually to coronary angiography to 50 cardiac asymptomatic patients with suspected vasculogenic ED Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751

12. Cardiovascular Disease in Patients with ED Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751  In 40 patients out of 50 (80%) there was presence of multiple risk factors for CAD  Family history(n=32)  cigarette smoking(n=40)  total cholesterol >200 mg/dl(n=35)  HDL-c <40 mg/dl(n=18)  Hypertension(n=24)  Sedentary life style(n=38)  diabetes(n=10)  Exercise ECG was positivein 28/50 pazients  Coronary angiography was performed in 20 patients and showed  proximal LAD or 3vd in 6 pts  2 vd in 7  Single vessel disease in 7 pts

13. ED and Cardiovascular Disease Pritzker MR. Circulation. 1999; 100 (suppl 1): I-711. Abstract 3751  Asymptomatic patients with vasculogenic ED have a high incidence of CAD and high prevalence of CAD risk factors  but only a minority undergoes cardiovascular screening  Screening for cardiovascular disease in patients with vasculogenic ED may help to identify patients at high risk of cardiovascular events

16. Acute Ischemic Syndromes Severe Heart Failure (NYHA IV) Severe malignant effort-induced tachy- arrhythmia Cardiac Contraindications to Sexual Activity ACC/AHA Clinical Statement

20. Myocardial Ischemia During Sexual Activity in Patients with CAD Drory et al Am J Cardiol 1995 All Patients with myocardial ischemia during sexual activity had also ischemia on Holter ECG monitoring

21. In 19 pts with CAD during sexual activity ß-blockers completely abolished ECG changes and symptoms Drory et al Am J Cardiol 1995 Myocardial Ischemia During Sexual Activity in Patients with CAD

27. Sildenafil Use and Myocardial Ischemia in Patients with CAD Exercise tolerance Ischemic treashold Effect of Sildenafil on Myocardial Ischemia Effect of Sildenafil on Myocardial Ischemia in patients with CAD on therapy

28. Chronic use of nitrats has no beneficial efect upon cardiovasular mortality and morbidity and therefore can be easily changed with other drugs for the treatment of CAD in those patients requiring Sildenafil Acute nitrate administration must be always performed under medical supervision and the dose must be adjusted according to the degree of peripheral vasodilation Use of Sildenafil in Patients with CAD Using NItrates

29. ** Effect of Sildenafil in Patients with CAD treated with ß-blockers Patrizi R. et al. It Heart J 2001

30. ** Effect of Sildenafil in Patients with CAD treated with ß-blockers Patrizi R. et al. It Heart J 2001

31. Effects on Primary/Secondary End Points *P<0.05 0 5 10 15 20 25 30 PlaceboSildenafil Time to limiting angina Time to angina Time to 1 mm ST-segment depression Exercise duration % change from baseline 4.7 9.8 4.7 17.3 20.4 26.5 3.9 8.7 * * * Fox KM et al Circulation 2001, abstract supplement

33. Trimetazidine and Nitrates on Total Ischemic Burden P=0.07 between treatments Rosano et al Eur Heart J 2003 (abstr)

34. Trimetazidine and Nitrates on Ischemic Episodes During Sexual Activity P<0.04 Rosano et al Eur Heart J 2003 (abstr)

35. Trimetazidine vs Nitrates on the Control of Anginal Episodes p<0.01 vs baseline p=0.048 vs nistrates p<0.01 vs baseline p<0.04 vs nistrates p<0.01 vs baseline Rosano et al Eur Heart J 2003 (abstr)

36. Trimetazidine plus Sildenafil vs Nitrates Positive Exercise Tests p<0.01p<0.05 Rosano et al Eur Heart J 2003 (abstr)

37. Trimetazidine plus Sildenafil vs Nitrates Heart Rate and Blood Pressure Rosano et al Eur Heart J 2003 (abstr)

38. Trimetazidine plus Sildenafil or Nitrates on Exercise Test Parameters P<0.01 for all comparisons TMZ+S vs Baseline P<0.05 for all comparisons TMZ+S vs Nitrates+P Rosano et al Eur Heart J 2003 (abstr)

39. Trimetazidine plus Sildenafil or Nitrates on ST segment Depression P=0.048

43. Conclusions Sildenafil has positive effect on cardiac haemodynamics and increase coronary blood flow The effect of Sildenafil on blood pressure is minimal Sildenafil has a positive effect on exercise-induced myocardial ischemia in patients with CAD The use of sildenafil in patients with myocardial ischemia well controlled by anti-anginal drugs is safe