American Heart Journal
Volume 155, Issue 1 , Pages 113.e1-113.e8, January 2008

A randomized, double-blind, placebo-controlled study of the safety and efficacy of intravenous MCC-135 as an adjunct to primary percutaneous coronary intervention in patients with acute myocardial infarction: Evaluation of MCC-135 for left ventricular salvage in acute myocardial infarction (EVOLVE)

  • Ik-Kyung Jang, MD, PhD

      Affiliations

    • Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • Corresponding Author InformationReprint requests: Ik-Kyung Jang, MD, PhD, Cardiology Division, Gray/Bigelow 800, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.
    • ,
  • Neil J. Weissman, MD

      Affiliations

    • Washington Hospital Center, Washington DC
    • ,
  • Michael H. Picard, MD

      Affiliations

    • Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • ,
  • Michael R. Zile, MD

      Affiliations

    • RHJ Department of Veterans Affairs Medical Center, and the Medical University of South Carolina, Charleston, SC
    • ,
  • Veronica Pettigrew, RN, BSN

      Affiliations

    • Mitsubishi Pharma America, Inc., Warren, NJ
    • ,
  • Steven Shen, PhD

      Affiliations

    • Mitsubishi Pharma America, Inc., Warren, NJ
    • ,
  • Jun Tatsuno, MSc

      Affiliations

    • Mitsubishi Pharma Corporation, Osaka, Japan
    • ,
  • Mark G. Hibberd, MD, PhD

      Affiliations

    • CardioCorp Cardiovascular Clinical Research, Lexington, MA
    • ,
  • Dan Tzivoni, MD

      Affiliations

    • Shaare Zedek Medical Centre, Jerusalem, Israel
    • ,
  • Frans J. Th. Wackers, MD

      Affiliations

    • Yale University Radionuclide CORE Laboratory, Yale University, New Haven, CT
    • ,
  • the EVOLVE Investigators

Received 11 April 2007; accepted 20 August 2007. published online 12 October 2007.

Objectives

The objective of the study was to test the hypothesis that intracellular calcium modulation by 5-methyl-2-[piperazin-1-yl] benzene sulfonic acid monohydrate (MCC-135 [Caldaret]; Mitsubishi Pharma Corporation, Osaka, Japan) would preserve left ventricular function and reduce infarct size in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).

Background

Calcium overload inside myocytes during ischemia and reperfusion not only affects myocardial function but also may be related to myocyte necrosis. MCC-135 is the first in a new class of agents that modulate intracellular calcium overload.

Methods

Patients with acute STEMI undergoing primary PCI were randomized into placebo, low-dose, and high-dose MCC-135 groups. The predefined target population was those with anterior myocardial infarction and pre-PCI TIMI grade flow 0 or 1. Left ventricular ejection fraction (LVEF) on Day 5 was the primary end point. Secondary end points included infarct size measured by single photon emission computed tomography and by serum cardiac markers. Patients were followed up to 30 days for clinical outcome.

Results

Among 500 patients enrolled, 141 qualified as the target population. In this target population, there was no difference in the LVEF between 3 groups (placebo: 47.0% ± 1.7% [mean ± SEM], the low dose: 47.4% ± 1.7%, the high dose: 45.1% ± 2.0%). The infarct size on day 5 was not significantly different between the groups. The composite clinical outcome occurred in 25.5% in the placebo group, in 19.2% in the low-dose group, and in 34.2% in the high-dose group during a 30-day follow-up period (P = nonsignificant). MCC-135 appeared to be safe and well tolerated.

Conclusion

There were no significant benefits of MCC-135 on preservation of LVEF and reduction of infarct size on day 5 in patients with STEMI undergoing primary PCI.

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 The study was supported by a grant from Mitsubishi Pharma Corporation, Osaka, Japan.

 Conflict of interest IKJ, MHP, MGH, and FJTW: members of the EVOLVE study scientific advisory committee and received honoraria; NJW, MHP, and FJTW: directors of core laboratory and received payment for their work; VP and SS: full-time employees of Mitsubishi Pharma America Ltd, Warren, NJ; JT: a full-time employee of Mitsubishi Pharma Corporation in Japan; IKJ, MZ, and MH: consultant to Mitsubishi Pharma America Ltd, Warren, NJ.

PII: S0002-8703(07)00706-5

doi:10.1016/j.ahj.2007.08.020

American Heart Journal
Volume 155, Issue 1 , Pages 113.e1-113.e8, January 2008

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