Prevention of Acute Myocardial Injury by Trimetazidine in Patients Hospitalized for COVID-19
Status:
Recruiting
Trial end date:
2021-04-30
Target enrollment:
Participant gender:
Summary
Acute myocardial injury has been a finding of variable frequency among patients diagnosed
with COVID-19. It is now recognized that cTnI levels are strongly associated with increased
mortality. The mechanisms underlying the myocardial injury remain unknown, and it is not
clear whether they reflect local/systemic inflammatory process and/or cellular ischemia.
Both myocardial ischemia and ventricular dysfunction result in dramatic changes in
mitochondrial oxidative metabolism. These changes involve an increase in the rate of
cytoplasmic anaerobic glycolysis to compensate for the decrease in mitochondrial adenosine
triphosphate (ATP) production. The rest of the mitochondrial oxidative metabolism originates
mainly from the β-oxidation of free fatty acids, which occurs at the expense of glucose
oxidation.
Trimetazidine is a competitive inhibitor of the enzyme 3-ketoacyl coenzyme A (CoA) long-chain
thiolase (3-KAT), the last enzyme involved in the oxidation of fatty acids. Stimulation of
glucose oxidation by trimetazidine results in a better coupling between glycolysis and
glucose oxidation, with a consequent decrease in lactate production and intracellular
acidosis, present in situations of myocardial ischemia or heart failure.
Thus, the PREMIER-COVID-19 study was designed to test the hypothesis that the use of
trimetazidine associated with usual therapy in patients admitted with a diagnosis of moderate
to severe acute respiratory syndrome by SARS-CoV2 infection reduces the extent of acute
myocardial injury assessed by the peak release of ultra-sensitive troponin compared to usual
therapy.