Safety and efficacy of intracoronary adenosine administration in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Abstract

Background: Studies evaluating intracoronary administration of adenosine for prevention of microvascular dysfunction and ischemic-reperfusion injury in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have yielded mixed results. Therefore, we performed a meta-analysis of these trials to evaluate the safety and efficacy of intracoronary adenosine administration in patients with AMI undergoing primary PCI. Methods: A total of seven prospective randomized controlled trials were analyzed. The endpoints extracted were post-procedure residual stent thrombosis (ST) segment elevation and ST segment resolutions (STRes), difference in peak creatine kinase (CK-MB) concentration, thrombolysis in myocardial infarction (TIMI) grade III flow (TIMI 3 flow), myocardial blush grade (MBG) 3, mean difference in post-PCI ejection fraction (EF), all-cause mortality, cardiovascular mortality, heart failure (HF) and major adverse cardiovascular event (MACE). Safety endpoints analyzed were bradycardia, second-degree atrioventricular block (AVB), ventricular tachycardia (VT), ventricular fibrillation (VF) and recurrence of chest pain (CP). The endpoints were analyzed by standard methods of meta-analysis. Results: Intracoronary adenosine therapy led to significantly more post-PCI STRes [relative risk (RR) 1.39, 95% confidence interval (CI) 1.01–1.90; p = 0.04] and reduction in residual ST segment elevation (RR 0.82, CI 0.69–0.99; p = 0.04) but did not improve TIMI 3 flow (RR 1.09, CI 0.94–1.27; p = 0.25), MBG3 (RR 1.04, CI 0.65–1.69; p = 0.88), peak CK-MB concentration (mean difference −39.43, CI −120.223 to 41.371; p = 0.339) and post-PCI EF (mean difference 1.238, CI −5.802 to 8.277; p = 0.730). There was a trend towards improvement and MACE (RR 0.64, CI 0.40–1.03; p = 0.06), incidence of HF (RR 0.47, CI 0.19–1.12; p = 0.08) and CV mortality (RR 0.15, CI 0.02–1.23; p = 0.08) that did not reach statistical significance but no difference in all-cause mortality (RR 0.77, CI 0.25–2.34; p = 0.64). Safety analysis showed no significant difference in CP events (RR 1.26, CI 0.55–2.86; p = 0.58), bradycardia (RR 2.19, CI 0.24–0.38; p = 0.49), VT (odds ratio 0.61, CI 0.08–4.90; p = 0.64) and VF (RR 0.49, CI 0.13–1.90; p = 0.30), but significantly more second-degree AVB (RR 7.88, CI 4.15–14.9; p < 0.01) in the adenosine group compared with the placebo group. Conclusion: Intracoronary adenosine administration was well tolerated and significantly improved electrocardiographic outcomes with a tendency towards improvement in MACE, HF and CV mortality that could not reach statistical significance.