Can we better protect patients who undergo revascularization?

Click to enlarge the figure

Click to enlarge the figure

While optimal medicamentous therapy is important in the treatment of patients with stable coronary artery disease (CAD), in some cases, prognostic and symptomatic benefit can only be achieved with myocardial revascularization procedures such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). However, mounting evidence with increasing use of these procedures shows that they may cause irreversible myocardial injuries despite successful myocardial revascularization. This paradox is referred to as ischemic-reperfusion injury and is due to the formation of free oxygen radicals in response to reperfusion of the ischemic myocardium. It induces an increase in biomarkers of necrosis, which has been reported to be associated with a high risk of death.^1,2

1. John PA, Ioannidis JP, Karvouni E, Katritsis DG. J Am Coll Cardiol. 2003;42:1406-1411.
2. Alexander JH, Hafley G, Harrington RA, et al; PREVENT IV Investigators. JAMA. 2005;294:2446-2454.

Click to enlarge the figure

One of the promising ways to provide cardioprotection in patients undergoing PCI and CABG may be the use of the antianginal drug trimetazidine. Trimetazidine is known to exert its anti-ischemic effect by providing the necessary ATP in the cardiomyocytes, thus promoting a decrease in intracellular acidosis and preventing intracellular calcium overload.

Prof Lopatin from Russia led two studies, including patients who were undergoing PCI or CABG, to identify potential short- and long-term beneficial effects of administration of trimetazidine MR at a dose of 70 mg/day for 2 weeks prior to the procedures, and during the 3 following years.

Click to enlarge the figure

In the study considering angina patients who underwent CABG,…

Click to enlarge the figure

Prof Lopatin showed that addition of trimetazidine MR

- for 3 years leads to a significantly more pronounced increase in left ventricular ejection fraction, meaning that trimetazidine MR enables a patient’s heart to continue contracting properly, which is essential to preserve quality of life. Other results in the study show that trimetazidine MR also provides higher exercise tolerance and a significant reduction in recurrence of angina pectoris.

Click to enlarge the figure

- In addition to that, administration of trimetazidine MR lowers levels of creatine kinase-MB isoenzyme (CK-MB) in the early postoperative period, showing that trimetazidine MR protects the myocardium and decreases myocardial damage during revascularization procedures.

Click to enlarge the figure

In the study considering angina patients who underwent PCI,…

Click to enlarge the figure

Prof Lopatin showed that addition of trimetazidine MR:

- for 3 years leads to a significant reduction in the rate of hospitalization for acute coronary syndromes, showing that trimetazidine MR has a strong cardioprotective effect. Other results show that trimetazidine significantly reduces repeat procedures of coronary revascularization, and that it also significantly increases left ventricular ejection fraction and exercise tolerance.

Click to enlarge the figure

- In addition to that, administration of trimetazidine MR lowers frequency of arrhythmias in the early postoperative period.

Click to enlarge the figure

During the last ESC Congress, Prof Lopatin went further and presented his 6-year long-term data with trimetazidine MR in post–myocardial infarction patients with stable angina and heart failure. These results were totally in line with the 2 previous studies, showing that long-term prescription of trimetazidine MR:

- significantly reduces the rate of MACE (cardiac death, nonfatal myocardial infarction, acute stroke, need for coronary revascularization, hospitalization for unstable angina or heart failure), and

- significantly reduces all-cause mortality.

Click to enlarge the figure

Prof Lopatin’s studies have highlighted the cardioprotective effect of trimetazidine MR, both in the short-term during revascularization and in the long-term (up to 6 years).