MITOCARE: Investigational agent failed to prevent reperfusion injury in STEMI

BARCELONA, Spain — Investigational drug TRO40303 failed to best placebo in reducing infarct size in a cohort of patients treated with primary PCI for STEMI, concluded findings from the MITOCARE study presented here.

Perspective from W. Douglas Weaver, MD

Dan Atar, MD, professor of cardiology, department of cardiology B, Oslo University Ulleval in Oslo, said that the investigational drug has demonstrated the capacity to reduce infarct size by 50% and have a positive impact on short- and long-term left ventricular ejection fraction in animal studies.

The aim of the current study was to investigate the safety and efficacy of TRO40303 for the treatment of reperfusion injury in STEMI patients in the PCI setting. Eligible participants were first-time STEMI patients who were presenting within 6 hours of pain onset and had a completely occluded lesion, according to Atar. Door-to-balloon time was an average of 38 minutes.

Dan Atar

“Patients were immediately randomized upon hospitalization,” Atar said during a presentation. He added that patients were evaluated for troponin I and CK at baseline and then at 6, 12, 18, 24, 36, 48 and 72 hours after stenting. Safety analyses and echocardiography were taken at 1 month.

There was no significant difference between placebo and TRO40303 (P=.9819) in terms of area under the curve (AUC) at 72 hours for CK u/L. A similar result was reported for the AUC for troponin I at that time point (P=.5699).

Myocardial salvage index was 0.58 (0.2-0.9) for placebo and 0.52 (0.2-0.8) for the study drug (P=.1). Infarct size expressed as percentage of the left ventricle was 0.15 (0-0.4) for placebo and 0.17 (0.1-0.4) for the study drug (P=.1034). Infarct sizes in grams were also similar — 20.01 grams (1.8-82.9) for placebo and 21.88 grams (3.1-62.1) for the study drug (P=1.650) — as were microvascular obstructions, which were 0.02 in both groups (P=.8512).

Other results indicated that LV end diastolic volume (placebo, 178.22 vs. TRO40303, 177.02; P=.9966), LV end systolic volume (placebo, 93.1 vs. TRO40303, 96.25; P=.6485) and LV ejection fraction (placebo, 0.48 vs. TRO40303, 0.46; P=.1526) were also not significantly different between groups.

“The MITOCARE trial did not show any protective effect of TRO40303 as compared to placebo in preventing reperfusion injury in STEMI patients treated with primary PCI,” Atar concluded. “A high standard of care accounted for the relatively small infarct size after primary PCI, and actually [left] little room for improvement. These results combined with the many failures in the field raise a provocative issue: whether reperfusion injury occurs at all in man, and, if it does, whether this type of injury really accounts for a significant part of the remaining infarct.”

The study was conducted at 10 centers in Denmark, France, Norway and Sweden between October 2011 and September 2013. – by Rob Volansky

For more information:

Atar D. MITOCARE study. Presented at: the European Society of Cardiology Congress; Aug. 30-Sept. 3, 2014; Barcelona, Spain.

Disclosure: Atar reports no relevant financial disclosures. The study was funded by the EU.

Perspective

W. Douglas Weaver, MD

There are other investigations going on right now of some very promising agents that really target mitochondrial function, so I would not dismiss this as a potential therapeutic pathway that might reduce infarct size in the future. I wouldn’t want to discourage the investigators who are working on mitochondrial specific agents for this and other cellular damage. In the last few years, quite a bit of evidence has surfaced showing that kidney injury and other acute injuries might be impacted by modifying these mitochondrial pathways. There is a lot of interest in that area right now.

W. Douglas Weaver, MD

Cardiology Today Editorial Board member

Past-President, American College of Cardiology

Disclosures: Weaver reports serving on the executive committee of a trial evaluating the use of a different agent to reduce infarct size for Stealth Peptides.