title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Chicago Medical School, 3333, Green Bay Road, North Chicago, IL 60068, USA. drmukeshsingh@yahoo.com
authors.forename: Mukesh
authors.initials: M
authors.lastname: Singh
authors.forename: Tejaskumar
authors.initials: T
authors.lastname: Shah
authors.forename: Kavia
authors.initials: K
authors.lastname: Khosla
authors.forename: Param
authors.initials: P
authors.lastname: Singh
authors.forename: Janos
authors.initials: J
authors.lastname: Molnar
authors.forename: Sandeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Rohit
authors.initials: R
authors.lastname: Arora
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D015906:Angioplasty, Balloon, Coronary; D017023:Coronary Angiography; D003326:Coronary Circulation; D003328:Coronary Thrombosis / Q000453:epidemiology; D052279:Creatine Kinase, MB Form / Q000032:analysis; D004562:Electrocardiography; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D015607:Stents; D013318:Stroke Volume; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D052279:Creatine Kinase, MB Form; D000241:Adenosine