CLINICAL RESEARCH: HEART FAILURE
A Randomized Clinical Trial of Trimetazidine, a Partial Free Fatty Acid Oxidation Inhibitor, in Patients With Heart Failure
Gabriele Fragasso, MD*,1,*,
Altin Palloshi, MD*,
Patrizia Puccetti, MD*,
Carmen Silipigni, MD*,
Alessandra Rossodivita, MD ,
Mariagrazia Pala, MD,
Giliola Calori, MDPhD*,
Ottavio Alfieri, MD* and
Alberto Margonato, MD, FESC*
* Clinical Cardiology-Heart Failure Unit, Istituto Scientifico-Universita Vita/Salute San Raffaele, Milan, Italy.
Cardiac Surgery, Istituto Scientifico-Universita Vita/Salute San Raffaele, Milan, Italy.
Manuscript received October 27, 2005;
revised manuscript received March 3, 2006,
accepted March 30, 2006.
* Reprint requests and correspondence: Dr. Gabriele Fragasso, Clinical Cardiology-Heart Failure Unit, Istituto Scientifico-Universita Vita/Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. (Email: gabriele.fragasso{at}hsr.it).
OBJECTIVES: This study sought to assess whether the long-term addition of trimetazidine to conventional treatment could improve functional class, exercise tolerance, and left ventricular function in patients with heart failure (HF).
BACKGROUND: Previous small studies have shown that trimetazidine may be beneficial in terms of left ventricular function preservation and control of symptoms in patients with post-ischemic HF.
METHODS: Fifty-five patients with HF were randomly allocated in an open-label fashion to either conventional therapy plus trimetazidine (20 mg three times daily) (28 patients) or conventional therapy alone (27 patients). Mean follow-up was 13 ± 3 months. At study entry and at follow-up, all patients underwent exercise testing and two-dimensional echocardiography. Among the others, New York Heart Association (NYHA) functional class and ejection fraction (EF) were evaluated.
RESULTS: In the trimetazidine group, NYHA functional class significantly improved compared with the conventional therapy group (p < 0.0001). Treatment with trimetazidine significantly decreased left ventricular end-systolic volume (from 98 ± 36 ml to 81 ± 27 ml, p = 0.04) and increased EF from 36 ± 7% to 43 ± 10% (p = 0.002). On the contrary, in the conventional therapy group, both left ventricular end-diastolic and -systolic volumes increased from 142 ± 43 ml to 156 ± 63 ml, p = 0.2, and from 86 ± 34 ml to 104 ± 52 ml, p = 0.1, respectively; accordingly, EF significantly decreased from 38 ± 7% to 34 ± 7% (p = 0.02).
CONCLUSIONS: In conclusion, long-term trimetazidine improves functional class and left ventricular function in patients with HF. This benefit contrasts with the natural history of the disease, as shown by the decrease of EF in patients on standard HF therapy alone.
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Abbreviations and Acronyms
| | ATP = adenosine triphosphate | | BNP = brain natriuretic peptide | | EDV = end-diastolic volume | | EF = ejection fraction | | ESV = end-systolic volume | | FFA = free fatty acids | | HF = heart failure | | METS = metabolic equivalent system | | NYHA = New York Heart Association |
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