Improving survivalin symptomatic ischemic patients with

left ventricular dysfunction

Beneficial effects oflong-term trimetazidine* therapy

Fragasso G et al. Int J Cardiol. In press.

Presented at AHA 2012

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.

What do preliminary data say?

Gaometa-analysis

n=61Patients 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.

Zhangmeta-analysis

A study with a homogeneous and relevantly sized population is needed.

METROStudy

El-KadyStudy

n=955Heart failure patients

n=200Angina patients with ischemic left ventricular dysfunction

2005 20092007 2012

Di NapoliStudy

n=353Angina patients with acute myocardial infarction

n=884Heart 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=65Patients with heart failure

2006

FragassoStudy

=> First results on mortality in a small population

Kim J et al. WCC 2012. Abstract 1621.

2006

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 patients669 Symptomatic heart failure patients

Fragasso G et al. Int J Cardiol. In press.

TMZ improves survival

TMZ significantly improves global survival by 11.3% (P=0.015).

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.

TMZ reduces global and cardiovascular mortality

Heart failure patients live longer with TMZ.Heart failure patients live longer with TMZ.

Fragasso G et al. Int J Cardiol. In press.

TMZ reduces rate of hospitalizationfor cardiovascular causes

Heart failure patients live better with TMZ.Heart failure patients live better with TMZ.

Fragasso G et al. Int J Cardiol. In press.

• 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.