Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy.
BACKGROUND
Trimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy.


METHODS
Sixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated.


RESULTS
Both in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 +/- 7 vs 41 +/- 9 and 45 +/- 8 vs 36 +/- 8%, P <.001 for both) and M value (4.0 +/- 1.8 vs 3.3 +/- 1.6, P =.003, and 3.5 +/- 1.5 vs 2.7 +/- 1.6 mg/kg body weight/min, P <.01) increased, while fasting blood glucose (121 +/- 30 vs 136 +/- 40, P =.02 and 125 +/- 36 vs 140 +/- 43, P =.19) and endothelin-1 (8.8 +/- 3.8 vs 10.9 +/- 3.8, P <.001 and 6.2 +/- 2.4 vs 9.2 +/- 4.3 pg/mL, P =.03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ (P =.019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved (P =.018 vs placebo).


CONCLUSIONS
In a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.
Clinical Cardiology-Heart Failure Unit, Universitá degli Studi di Milano, Istituto Scientifico/Universitá San Raffaele, Milano, Italy. gabriele.fragasso@hsr.it
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Fragasso
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Piatti Md
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Monti
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Palloshi
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Setola
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Puccetti
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Calori
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Lopaschuk
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Margonato
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004452:Echocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D014292:Trimetazidine / Q000627:therapeutic use*
D005947:Glucose; D014292:Trimetazidine