title: Trimetazidine potentiates the effects of exercise training in patients with ischemic cardiomyopathy referred for cardiac rehabilitation.
abstract: BACKGROUND
  Patients referred for cardiac rehabilitation may take advantage from combining trimetazidine (TMZ) with exercise training (ET), as both treatments produce similar effects in the cardiovascular system. It is, however, unknown whether the combination of TMZ with ET may determine greater improvements in functional capacity and endothelial function than ET alone.
  
  
  METHODS
  A randomized longitudinal controlled study.
  
  
  METHODS
  We studied 116 patients (97 men and 19 women, mean age 58+/-9 years) with ischemic heart disease and left ventricular dysfunction who were referred for cardiac rehabilitation. Coronary risk factors were present in 82 patients (diabetes in 28 patients). Patients were randomized into three matched groups. A group (TMZ+training, TT, n=30) received TMZ at doses of 20 mg three times daily orally for 8 weeks in addition to standard medications and underwent a supervised program of ET at 60% of oxygen uptake at peak, three times a week for 8 weeks. A group (exercise, E, n=30) completed the ET program without receiving TMZ. A control group (C, n=26) was neither exercised nor received TMZ. A fourth group (TMZ, n=30) receiving TMZ 20 mg three times daily for 8 weeks was also studied. On study entry and at 8 weeks all patients underwent echocardiography, cardiopulmonary exercise testing, and vasomotor reactivity of the brachial artery.
  
  
  RESULTS
  Oxygen uptake at peak was significantly increased in the TT (25%), TMZ (15.1%), and E group (15.3%) (P<0.001 TT vs. C; P<0.05 vs. TMZ and E). Left ventricular ejection fraction was also improved in TT (18.4%), TMZ (15.7%), and E (12.9%) (P<0.001 TT vs. C; P<0.05 vs. TMZ and E), as a result of reduction in end-systolic volume. The endothelium-dependent dilation was similarly improved (P<0.001 TMZ vs. C; P<0.05 vs. TMZ and E). The most significant improvements were observed in the subgroup TT with multiple risk factors.
  
  
  CONCLUSIONS
  The addition of TMZ to ET determined greater improvements in functional capacity, left ventricular ejection fraction, and endothelium-dependent dilation than TMZ or ET given alone. No differences between improvements after TMZ and E as compared with controls were observed.
authors.affiliation: Cardiac Rehabilitation and Prevention, Lancisi Heart Institute, Ancona, Italy. r.belardinelli@ao-umbertoprimo.marche.it
authors.forename: Romualdo
authors.initials: R
authors.lastname: Belardinelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Lacalaprice
authors.forename: Ernesto
authors.initials: E
authors.lastname: Faccenda
authors.forename: Loretta
authors.initials: L
authors.lastname: Volpe
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology / Q000534:rehabilitation*; D003131:Combined Modality Therapy; D018619:Echocardiography, Doppler, Pulsed; D004562:Electrocardiography; D005080:Exercise Test; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology / Q000534:rehabilitation*; D010101:Oxygen Consumption / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014292:Trimetazidine / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology / Q000534:rehabilitation*
chemical_list: D015415:Biomarkers; D014665:Vasodilator Agents; D014292:Trimetazidine