title: Trimetazidine improves exercise performance in patients with peripheral arterial disease.
abstract: Trimetazidine, an inhibitor of free fatty acids (FFA) oxidation, shifts cardiac and muscle metabolism from FFA to glucose utilization. This effect results in a greater production of high energy phosphates and ultimately into an anti-ischemic effect. Whether the anti-ischemic cardiac effects of trimetazidine (TMZ) can be translated to skeletal muscle in patients with claudication is unknown. We investigated the effectiveness of TMZ on functional performance in patients with peripheral arterial disease (PAD) and claudication. One hundred patients with claudication were enrolled in a parallel, double-blind, 3 months study. Patients were randomized to receive TMZ or matching placebo and were included in a domiciliary exercise program, consisting in daily sessions of aerobic and isotonic exercise for at least five days a week. All patients underwent a treadmill test, evaluating maximal walking distance (MWD), and ankle-brachial index (ABI) at baseline and after 3 months. ABI was similar in the two groups at baseline and did not significantly change at the end of the study in either groups (0.83+0.04 vs 0.85+0.03, TMZ vs placebo, respectively). MWD improved in all patients with exercise training; however, a greater improvement in MWD was observed with TMZ compared to placebo (23% vs 14%, p<0.0001). Physical training ameliorates functional performance in PAD. The adjunct of TMZ to exercise induces a greater improvement in MWD, suggesting that the inhibition of FFA oxidation improves functional capacity in patients with PAD and claudication.
authors.affiliation: Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Via Della Pisana, 235, 00163 Rome, Italy. cristiana.vitale@gmail.com
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marazzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pelliccia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Volterrani
authors.forename: Elena
authors.initials: E
authors.lastname: Cerquetani
authors.forename: Ilaria
authors.initials: I
authors.lastname: Spoletini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mercuro
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Valentina
authors.initials: V
authors.lastname: Dall'Armi
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D015444:Exercise; D005080:Exercise Test; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D014292:Trimetazidine