515 adenosine as adjunctive therapy in patients with acute coronary syndrome: when less is more. an updated meta-analysis of 26 randomized controlled trials.

Abstract Background Percutaneous coronary intervention (PCI) is the milestone of treatment for patients with acute coronary syndrome (ACS). However, a considerable number of patients do not achieve a complete myocardial reperfusion since coronary microvascular obstruction (CMVO) might occur. Adenosine is one of the pharmacological strategies tested in several randomized controlled trials (RCTs) to minimize the incidence of CMVO. However, conflicting results have been reported so far. The aim of the present study was to evaluate all the RCTs comparing intracoronary or intravenous adenosine versus placebo as adjunctive therapy in patients with ACS undergoing PCI or thrombolysis. Methods PubMed and Scopus electronic databases were scanned for eligible studies up to June 5th, 2022. Our meta-analysis included 26 randomized RCTs with a total of 5843 patients involved. Primary endpoints were the rate of clinical events, defined as major adverse cardiovascular events (MACE), heart failure (HF), all-cause-death and non-fatal myocardial infarction (MI). The rate of advanced atrioventricular (AV) blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were considered as safety endpoints. Further subgroup analyses and meta regressions were conducted to evaluate the role of different procedural and non-procedural factors influencing the results. Finally, a secondary analysis was conducted only including RCTs enrolling patients with ST-segment elevation myocardial infarction (STEMI). Results Adenosine administration did not confer any significant clinical benefit in terms of reduction of MACE (RR 0.91 CI 0.79-1.05, p 0.16), all-cause-death (RR 0.90 CI0.74-1.09, p 0.28), non-fatal MI (RR 1 CI 0.74 - 1.35, p 0.44) and HF (RR 0.94 CI 0.77-1.16, p 0.59). Remarkably, adenosine was associated with a significant reduction of post-procedural CMVO parameters such as Myocardial Blush Grade (MBG) 0-1 (RR 0.69 CI 0.53-0.90, p 0.01) and Thrombolysis In Myocardial Infarction (TIMI) flow grade 0-2 (RR 0.67 CI 0.53-0.85, p <0.01), when compared to placebo. Secondary analyses of STEMI patients showed similar results. As regards safety, adenosine therapy was associated with a higher rate of advanced AV blocks (RR 2.72 CI 1.57-4.74, p <0.01). A higher rate of VF/SVT was observed with adenosine in studies with total mean ischemic time >3 hours (RR 1.67 CI 1.14-2.42) Conclusions This is the most up-to-date meta-analysis summarizing the available evidence on adenosine safety and efficacy in the prevention or treatment of CMVO in ACS patients. Although adenosine improves surrogate parameters of myocardial perfusion, its use does not provide any clinical benefits. Additionally, adenosine infusion increases the risk of advanced AV blocks. Moreover, a longer ischemic time seems to be associated with a higher rate of adenosine-triggered ventricular arrhythmias, suggesting that higher myocardial ischemic damage may represent a substrate for adenosine arrhythmogenic effects.