Phase 2 studies of adenosine cardioplegia

Area of Science:

• Cardiovascular Surgery
• Pharmacology
• Clinical Trials

Background:

• Laboratory studies suggested benefits of adenosine-supplemented cardioplegia.
• Phase 1 trials indicated safe administration of adenosine with warm blood cardioplegia at 15 mumol/L.
• Phase 2 studies were recommended based on initial safety and tolerability data.

Purpose of the Study:

• To evaluate the efficacy of adenosine-supplemented warm blood cardioplegia in patients undergoing coronary artery bypass graft (CABG) surgery.
• To determine if adenosine improves clinical outcomes compared to placebo in CABG patients.
• To assess different concentrations of adenosine (15, 50, and 100 mumol/L) in two randomized controlled trials.

Main Methods:

• Two double-blind, randomized, placebo-controlled trials were conducted.
• Patients received adenosine (15, 50, or 100 mumol/L) or placebo with warm antegrade blood cardioplegia during primary, isolated CABG surgery.
• Data from both trials were combined via meta-analysis using Mantel and Haenszel methods.

Main Results:

• No statistically significant differences were observed in primary outcomes (death, myocardial infarction, low output syndrome) or secondary outcomes between adenosine and placebo groups.
• Meta-analysis showed no consistent treatment benefit for adenosine supplementation (e.g., RR for death = 1.02, 95% CI = 0.06-16.6).
• All study groups were comparable in preoperative characteristics, angiographic findings, and intraoperative variables.

Conclusions:

• Adenosine supplementation of warm blood cardioplegia did not provide statistically significant clinical benefits in elective CABG surgery.
• Despite promising preclinical data, adenosine did not improve patient outcomes in this surgical context.
• Interim analyses suggest that larger sample sizes are unlikely to reveal significant clinical differences.