Effects of endothelin A receptor blockade in patients with ST-elevation acute coronary syndrome--a rhythmologic substudy

Aims: Ventricular arrhythmias are common after acute myocardial infarction (AMI). Endothelin (ET) is a mediator of microvascular dysfunction and cardiac remodeling with arrhythmogenic potential. The aim of this study was to assess safety and feasibility of selective ET-A receptor blockade in ST-elevation acute coronary syndrome (STE-ACS) within a larger randomized trial.

Main methods: Patients with posterior-wall STE-ACS were randomly assigned to receive intravenous BQ-123 at 400 nmol/min or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention. Twenty-four hour Holter recordings were performed during hospitalization for STE-ACS and after 6-8 weeks. The predefined primary endpoint was the documentation of ventricular tachycardia and/or late potentials at follow-up.

Key findings: There was no significant difference in the predefined primary endpoint at 45 (33-62) days (0/16 (0%) in BQ-123 treated patients vs. 1/14 (7%) in the placebo group, p=0.465). At 2 (1-3) days, an increase in the total number of supraventricular extrasystoles (SVES)/24 h in patients randomized to BQ-123 (45 (17-165) beats vs. 11 (5-72) beats in placebo treated patients, p=0.025) occurred. This increase was also observed at 45 days (105 (37-216) beats vs. 11 (3-98) beats in placebo treated patients, p=0.037). There was no significant difference regarding other rhythmologic secondary endpoints between the two groups.

Significance: Based on the analysis of long-term ECG data, short-term administration of BQ-123 after AMI was safe. Because of the small sample size, no firm conclusion regarding antiarrhythmic efficacy can be drawn.