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)

Abstract

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.