Adenosine as adjunctive therapy, compared with placebo, in patients with acute coronary syndrome (ACS) and history of percutaneous coronary intervention or thrombolysis is associated with an increased risk for advanced atrioventricular blocks and an increased rate of ventricular arrhythmias in patients with long ischemic time. These findings were published in the European Heart Journal—Cardiovascular Pharmacotherapy.
Researchers conducted a meta-analysis to assess the efficacy and safety of adenosine vs placebo in patients with ACS who received percutaneous coronary intervention or thrombolysis. A systematic review was performed for all relevant randomized controlled trials (RCTs) in PubMed and Scopus.
Efficacy endpoints included major adverse cardiac events (MACE), all-cause death, nonfatal myocardial infarction, and heart failure. The rates of advanced atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were safety endpoints.
A total of 26 studies with 5843 patients were included in the meta-analysis. The mean follow-up was 7 months, the weighted mean age of participants was 60.6±2.4 years, 70.5% of the patients were men, and 19.8% had diabetes.
Adenosine therapy demonstrated no clinical advantage in any efficacy endpoint vs placebo in pooled analysis of the following factors:
- MACE (risk ratio [RR], 0.91; 95% CI, 0.79-1.05; P =.16)
- All-cause-death (RR, 0.90; 95% CI, 0.74-1.09; P =.28)
- Nonfatal myocardial infarction (RR, 1.0; 95% CI, 0.74-1.35; P =.44)
- Heart failure (RR, 0.94; 95% CI, 0.77-1.16; P = .59)
Adenosine was associated with an increased rate of advanced atrioventricular block (RR, 2.72; 95% CI, 1.56-4.74; P <.01) vs placebo, and a similar rate of VF/SVT was observed between the 2 groups (RR, 1.19, 95% CI, 0.74-1.90; P =.48).
Among secondary endpoints, adenosine was not associated with improvement in left ventricular ejection fraction (effect size [ES], 0.22; 95% CI, -0.04 to 0.47; P =.10) or reduced infarct size (ES, -0.09; 95% CI, -0.35 to 0.18; P =.53). A trend was found regarding an increased rate of ST-segment resolution in the adenosine group (RR, 1.11; 95% CI, 1.00-1.22; P =.05). Myocardial blush grade 0 to 1 (RR, 0.69; 95% CI, 0.53-0.90; P =.01) and thrombolysis in myocardial infarction flow grade 0 to 2 (RR, 0.67; 95% CI, 0.53-0.85; P <.01) were lower in the adenosine group.
In subgroup analysis using a mean ischemic time longer than 3 hours, a significantly higher rate of VF/SVT occurred in the adenosine-treated group (RR, 1.66; 95% CI, 1.14-2.42). In addition, a higher VF/SVT rate was observed in the studies in which adenosine was administered intravenously (RR, 1.19; 95% CI, 1.09-1.90).
Among several limitations, most of the RCTs are designed for surrogate endpoints, and the meta-analysis may be underpowered to detect significant differences in hard clinical endpoints. Also, different definitions for MACE and heart failure are used in the studies, which causes differences in the event rate reported.
“Despite improving surrogate parameters of myocardial perfusion, adenosine is not associated with any clinical benefit compared to placebo,” the investigators wrote.
Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Laborante R, Bianchini E, Restivo A, et al. Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials Eur Heart J Cardiovasc Pharmacother. Published online December 10, 2022. doi: 10.1093/ehjcvp/pvac069