1. Improving survival in symptomatic ischemic patients with left ventricular dysfunction Beneficial effects of long-term trimetazidine* therapy Fragasso G et al. Int J Cardiol. In press. Presented at AHA 2012 *Trimetazidine is indicated by the European Medecines Agency (EMA) as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies.

2. What do preliminary data say? Gao meta-analysis n=61 Patients with severe ischemic cardiomyopathy El Kady T et al. Am J Cardiovasc Drugs. 2005;5:271-278. Di Napoli P et al. J Cardiovasc Pharmacol. 2007;50:585-589. Fragasso et al. J Am Coll Cardiol. 2006;48:992-998. Iyengar S et al. Am J Cardiovasc Drugs. 2009;9:293-297. Gao D et al. Heart. 2011;97(4):278-286. Zhang L et al. J Am Coll Cardiol. 2012;59:913-922. Zhang meta-analysis A study with a homogeneous and relevantly sized population is needed. METRO Study El-Kady Study n=955 Heart failure patients n=200 Angina patients with ischemic left ventricular dysfunction 2005 200920072012 Di Napoli Study n=353 Angina patients with acute myocardial infarction n=884 Heart failure patients => First data on mortality evaluated as a safety parameter => Complemen- tary results on mortality in a small population => Primary objective was to assess the 6-month survival rate 2011 => First meta- analysis demonstrating mortality results n=number of patients. n=65 Patients with heart failure 2006 Fragasso Study => First results on mortality in a small population Kim J et al. WCC 2012. Abstract 1621. 2006

3. A new study designed to evaluate survival International multicenter retrospective cohort study Inclusion criteria: – Ejection fraction ≤ 45% – NYHA Class II-IV – Trimetazidine (TMZ) administered if symptoms persist despite correct titration of standard medical therapy for chronic heart failure (CHF) CHF was of ischemic origin in >80% of patients Mean follow-up: 3 years Propensity score 669 Symptomatic heart failure patients Fragasso G et al. Int J Cardiol. In press.

4. TMZ improves survival TMZ significantly improves global survival by 11.3% (P=0.015). Global survival Event-free survival Fragasso G et al. Int J Cardiol. In press.

5. TMZ reduces global and cardiovascular mortality Heart failure patients live longer with TMZ. Fragasso G et al. Int J Cardiol. In press.

6. TMZ reduces rate of hospitalization for cardiovascular causes Heart failure patients live better with TMZ. Fragasso G et al. Int J Cardiol. In press.

7. The addition of TMZ to standard medical therapy in patients with CHF significantly reduces total and cardiovascular mortality and improves event-free survival. Therefore, this study confirms in a homogeneous and relevantly sized population that TMZ should be considered as a potential additional medication to standard therapy in CHF patients. These results could be explained by the ability of TMZ to reduce ischemia whatever the causal mechanism, and therefore to protect the heart from subsequent damage. Conclusion: Fragasso G et al. Int J Cardiol. In press.