Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction

Area of Science:

• Cardiology
• Pharmacology
• Immunology

Background:

• Inflammation post-ST-segment elevation myocardial infarction (STEMI) influences infarct size and cardiac remodeling.
• Mammalian target of rapamycin (mTOR) pathway inhibition shows promise in preclinical models for reducing MI size.

Purpose of the Study:

• To evaluate the efficacy of mTOR inhibition via everolimus in reducing myocardial infarct size and microvascular obstruction in STEMI patients undergoing primary percutaneous coronary intervention (PCI).

Main Methods:

• The randomized, double-blind, placebo-controlled CLEVER-ACS trial enrolled 150 STEMI patients undergoing PCI.
• Patients received either oral everolimus or placebo for 5 days.
• Primary endpoint: change in MI size; Secondary endpoint: change in microvascular obstruction (MVO) assessed by cardiac MRI at 30 days.

Main Results:

• Everolimus did not significantly reduce MI size compared to placebo (-14.2 g vs. -12.3 g; P=0.99).
• No significant difference was observed in the reduction of MVO between the everolimus and placebo groups (-4.8 g vs. -6.3 g; P=0.14).
• Adverse event rates were similar between the groups.

Conclusions:

• Early mTOR inhibition with everolimus did not improve myocardial infarct size or microvascular obstruction in STEMI patients treated with primary PCI.
• The findings suggest that targeting mTOR in this manner may not be beneficial for acute MI treatment in humans.