Number 27, 2005
Metabolic approach in heart failure

Vastarel MR: an innovative metabolic approach to ischemic heart failure

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Elena Louette
192 av. Charles-de-Gaulle, 92200 Neuilly-sur-Seine, France
Correspondence: Dr Elena Louette, MD, 192 av. Charles-de-Gaulle, 92200 Neuilly-sur-Seine, France. E-mail: elena-liliana louette@fr.netgrs.com

Introduction
Heart failure can be regarded as the final outcome of many cardiovascular disorders, among which cardiomyopathies related to ischemia, hypertension and valvular disorders are predominant [1].
Although substantial progress has been made over the past years in the treatment of heart failure, the quality of life and the prognosis of heart failure patients remains very poor. Current medical therapy for patients with heart failure is mainly based on conventional drugs such as angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, and aldosterone inhibitors. However new treatments targeting other pathological mechanisms need to be given more consideration.
Since metabolism and function in the heart are closely interdependent, energy substrate metabolism is a logical target when seeking to improve the function of the failing heart [2]. In heart failure, myocardial metabolism shifts toward increased oxidation of free fatty acids, which is energy-consuming compared with glucose oxidation. The metabolic agent trimetazidine (Vastarel MR) is able to restore and optimize cardiac energy metabolism in myocardial cells by making metabolism revert from fatty acid oxidation to glucose oxidation.
Trimetazidine is a 3-ketoacyl coenzyme A (CoA) thiolase (3-KAT) inhibitor which following twice-daily administration reduces fatty acid ß-oxidation via selective inhibition of mitochondrial long chain 3-ketoacyl coenzyme A thiolase (Figure 1). This results in a shift towards glucose oxidation and better use of the energy supply, thus reducing ischemia-induced metabolic damage.

Trimetazidine provides major anti-ischemic efficacy and improves left ventricular function in patients with ischemic cardiomyopathy
In a recent study, Vitale et al [10] assessed the effect of Vastarel on cardiac function in elderly patients with left ventricular dysfunction after 6 months of treatment. The results showed that Vastarel resulted in a significant reduction in episodes of anginal attacks (P<0.01) and the consumption of nitroglycerin (P<0.01) (Figure 2), while simultaneously improving myocardial contractile function.

Trimetazidine, added to standard medical therapy, provides long-term benefits in patients with left ventricular dysfunction and ischemic cardiomyopathy
More recently, Di Napoli et al [11] have shown that long-term treatment with Vastarel provides clear clinical benefits in patients with left ventricular dysfunction and ischemic cardiomyopathy. Sixty-one patients were allocated randomly to groups either to receive Vastarel in addition to their conventional treatment or to continue their usual therapy for 18 months. They were evaluated at baseline and at 6, 12, and 18 months. In patients in the Vastarel group, an increase in left ventricular ejection fraction (LVEF) was reported, starting at 6 months and maintained after 12 and 18 months of treatment (from 30% at baseline, 32% at 6 months, 38% at 12 months, and 37% at 18 months). In contrast, LVEF deteriorated in the control group during the same period (from 31% at baseline to 30%, 28%, and 26%, respectively) (Figure 3).

Conclusion
Modified-release trimetazidine (Vastarel MR), the first 3-KAT inhibitor which, under ischemic conditions, shifts energy production from fatty acids to glucose oxidation, benefits a wide range of coronary patients, from stable angina to ischemic cardiomyopathy. Increasing evidence supports the importance of a metabolic treatment such as Vastarel MR, in optimizing cardiac metabolism and improving the working efficiency of the failing heart. This novel approach to the management of heart failure suggests that metabolic therapy added to conventional treatment, is an important step towards achieving “optimal treatment_ and better prognosis in these severe coronary patients. ?

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REFERENCES

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