Effect of inhibition of the Na+/H+ exchanger with cariporide on left ventricular function in acute coronary syndromes: results from the echocardiographic substudy of the GUARDIAN trial.
OBJECTIVE
To evaluate the effects of inhibition of the Na+/H+ exchanger (NHE) on regional left ventricular dysfunction in patients with a non-ST elevation acute coronary syndrome (ACS) BACKGROUND: NHE inhibition protects against myocardial necrosis and stunning in ischemia-reperfusion models.


RESULTS
In a substudy of the GUARd During Ischemia Against Necrosis (GUARDIAN) trial, 141 patients with an ACS and wall motion abnormalities on a baseline echocardiogram underwent repeated studies after 48 h and 36 days to determine the extent of early and late recovery of ventricular function. Patients were randomized to cariporide 20 mg, 80 mg or 120 mg intravenously three times per day or placebo for two to seven days. The wall motion score index improved from baseline to day 36 by 0.13+/-0.21, 0.16+/-0.34 and 0.15+/-0.28, respectively, in the cariporide groups, and by 0.10+/-0.16 with placebo (P=0.57). From baseline to 48 h, the wall motion score index decreased by 0.04+/-0.16, 0.08+/-0.20 and 0.03+/-0.22, respectively, for the cariporide groups and by 0.03+/-0.11 with placebo (P=0.09); the number of abnormal chords (centreline method) decreased by 11.2+/-24.0, 9.5+/-24.3 and 8.1+/-27.9, respectively, in the cariporide groups compared with an increase of 0.6+/-20.0 with placebo (P=NS).


CONCLUSIONS
No significant benefit of NHE inhibition could be detected in ACS patients in the GUARDIAN trial.
Tardif
Jean-Claude
JC
Department of Medicine, Montreal Heart Institute, Montreal, Quebec. jean-claude.tardif@icm.mhi.org
Mercier
Lise-Andrée
LA
Théroux
Pierre
P
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide