Randomized Trial of Early mTOR Inhibition in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Stähli, Barbara E; Klingenberg, Roland; Heg, Dik; Branca, Mattia; Manka, Robert; Kapos, Ioannis; Müggler, Oliver; Denegri, Andrea; Kesterke, Rahel; Berger, Florence; Stehli, Julia; Candreva, Alessandro; von Eckardstein, Arnold; Carballo, David; Hamm, Christian; Landmesser, Ulf; Mach, François; Moccetti, Tiziano; Jung, Christian; Kelm, Malte; ... (2022). Randomized Trial of Early mTOR Inhibition in Patients with Acute ST-Segment Elevation Myocardial Infarction. Journal of the American College of Cardiology, 80(19), pp. 1802-1814. Elsevier 10.1016/j.jacc.2022.08.747

Preview	Text 1-s2.0-S073510972206613X-main.pdf - Accepted Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (795kB) | Preview
	Text St_hli_JAmCollCardiol_2022.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (1MB)

BACKGROUND

Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI.

OBJECTIVES

The Controlled Level EVERolimus in Acute Coronary Syndromes trial (CLEVER-ACS) evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI.

METHODS

CLEVER-ACS was a randomized, multicenter, international, double-blind, placebo-controlled trial. A total of 150 patients with STEMI undergoing PCI were randomly assigned to oral everolimus (days 1-3: 7.5 mg qd, days 4-5: 5.0 mg qd) or placebo for 5 days. The primary endpoint was the change in myocardial infarct size, the secondary endpoint the change in microvascular obstruction (MVO) from baseline (12 hours - 5 days after PCI) to 30 days as assessed by cardiac magnetic resonance imaging (CMR).

RESULTS

The changes in MI size from baseline to 30 days, the primary endpoint, were -14.2 (95% CI -17.4 to -11.1) g and -12.3 (95% CI -16.0 to -8.7) g in the everolimus and placebo groups (p=0.99). Corresponding changes in MVO were -4.8 (-6.7 to -2.9) g and -6.3 (-8.7 to -4.0) g in the everolimus and placebo groups (p=0.14). Adverse events did not differ between the study groups.

CONCLUSIONS

Among STEMI patients undergoing PCI, early mTOR inhibition with everolimus did not reduce MI size or MVO at 30 days.

Interest & Impact

Downloads

71 since deposited on 05 Sep 2022
69 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item