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).
OBJECTIVE
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.


CONCLUSIONS
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.
Jang
Ik-Kyung
IK
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ijang@partners.org
Weissman
Neil J
NJ
Picard
Michael H
MH
Zile
Michael R
MR
Pettigrew
Veronica
V
Shen
Steven
S
Tatsuno
Jun
J
Hibberd
Mark G
MG
Tzivoni
Dan
D
Wackers
Frans J Th
FJ
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D001557:Benzenesulfonates / Q000008:administration & dosage*; D006328:Cardiac Catheterization; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D010879:Piperazines / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D016879:Salvage Therapy; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
D001557:Benzenesulfonates; C434457:MCC 135; D010879:Piperazines