Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: results from an international multicentre retrospective cohort study.
OBJECTIVE
The aim of this cohort study was to retrospectively evaluate, in patients with chronic heart failure (CHF), the long term effect of trimetazidine (TMZ) on morbidity and mortality.


BACKGROUND
Previous small studies in patients with CHF have shown that TMZ can improve left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced.


METHODS
In this international multicentre retrospective cohort study data from 669 patients were analyzed. 362 patients were on TMZ due to symptom persistence despite up-titration of optimal CHF therapy, while the remaining patients continued conventional CHF therapy alone. Propensity score analysis was performed in order to minimize selection bias between the two groups.


RESULTS
Kaplan-Meier analysis for global mortality showed 11.3% improved global survival (p=0.015) and 8.5% improved survival for cardiovascular (CVD) death (p=0.050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a hazard ratio (HR)=0.189 (confidence interval - CI 95%: 0.017-0.454; p=0.0002). TMZ also showed a good risk reduction profile for CVD death causes (HR=0.072, CI 95%: 0.019-0.268, p=0.0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p<0.0005) with increased hospitalization-free survival of 7.8 months.


CONCLUSIONS
TMZ is effective in reducing mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long term survival in CHF patients.
Heart Failure Unit, Istituto Scientifico Ospedale San Raffaele, Milano, Italy. Electronic address: gabriele.fragasso@hsr.it.
Gabriele
G
Fragasso
Department of Medical Sciences, IRCCS San Raffaele, Roma, Italy.
Giuseppe
G
Rosano
Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Sang Hong
SH
Baek
Department of General and Invasive Cardiology, University Hospital 1, Yerevan State Medical University, Yerevan, Armenia.
Hamayak
H
Sisakian
SMDN, Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L'Aquila, Italy.
Pericle
P
Di Napoli
Heart Failure Unit, Istituto Scientifico Ospedale San Raffaele, Milano, Italy.
Luca
L
Alberti
Heart Failure Unit, Istituto Scientifico Ospedale San Raffaele, Milano, Italy.
Giliola
G
Calori
Severance Hospital, Yonsei University, Seoul, South Korea.
Seok-Min
SM
Kang
Department of General and Invasive Cardiology, University Hospital 1, Yerevan State Medical University, Yerevan, Armenia.
Laura
L
Sahakyan
Department of General and Invasive Cardiology, University Hospital 1, Yerevan State Medical University, Yerevan, Armenia.
Armen
A
Sanosyan
Department of Medical Sciences, IRCCS San Raffaele, Roma, Italy.
Cristiana
C
Vitale
Department of Medical Sciences, IRCCS San Raffaele, Roma, Italy.
Giuseppe
G
Marazzi
Heart Failure Unit, Istituto Scientifico Ospedale San Raffaele, Milano, Italy.
Alberto
A
Margonato
Cardiac Rehabilitation, Cardiology Division "GM Lancisi", Azienda Ospedali Riuniti, Ancona, Italy.
Romualdo
R
Belardinelli
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D010084:Oxidation-Reduction / Q000187:drug effects; D012189:Retrospective Studies; D016896:Treatment Outcome; D014292:Trimetazidine / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D005227:Fatty Acids; D014665:Vasodilator Agents; D014292:Trimetazidine