BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST segment elevation myocardial infarction. Although there is restoration of coronary flow after PPCI, impaired myocardial perfusion (known as no-reflow) is frequently observed, and is related to poor clinical outcomes. In order to overcome this phenomenon, drugs have been tried as adjunctive treatments to PPCI. Among them, verapamil and adenosine are two of the most promising drugs. There are no systematic reviews of these two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. OBJECTIVES: To study the impact of adenosine and verapamil on people with AMI who are undergoing PPCI. SEARCH METHODS: We searched the following databases in February 2012: the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, Web of Science and BIOSIS, China National Knowledge Infrastructure, Clinical Trials registers (Clinical Trials.gov, Current Controlled Trials, Australian & New Zealand Clinical Trials Registry, the WHO International Clinical Trials Registry Platform). We also handsearched the American Journal of Cardiology. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) where adenosine or verapamil was the primary intervention. Participants were individuals diagnosed with AMI who were undergoing PPCI. DATA COLLECTION AND ANALYSIS: Two review authors collected studies and extracted data. Where necessary, we contacted the trial authors to obtain the relevant information. We calculated risk ratios (RRs), P values, and 95% confidence intervals (CIs) of dichotomous data. MAIN RESULTS: We included 10 RCTs involving 939 participants in our review. Nine RCTs were associated with adenosine and one with verapamil. We considered the overall risk of bias of included studies to be moderate. There was no evidence that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.23 to 1.61, P = 0.32), long-term all-cause mortality (RR 1.20, 95% CI 0.27 to 5.22, P = 0.81), short-term non-fatal myocardial infarction (RR 1.38, 95% 0.28 to 6.96, P = 0.69) or the incidence of angiographic no-reflow (TIMI flow grade < 3 after PPCI: RR 0.72, 95% CI 0.49 to 1.07, P = 0.11, and myocardial blush grade (MBG) 0 to 1 after PPCI: RR 0.96, 95% CI 0.76 to 1.22, P=0.75). But the incidence of adverse events with adenosine, such as bradycardia (RR 6.57, 95% CI 2.94 to 14.67, P<0.00001), hypotension (RR 11.43, 95% CI 2.75 to 47.57, P=0.0008) and atrioventricular (AV) block (RR 6.67, 95% CI 1.52 to 29.21, P=0.01) was significantly increased.Meta-analysis of verapamil as treatment for no-reflow during PPCI was not calculated due to lack of data. AUTHORS' CONCLUSIONS: We found no evidence that adenosine and verapamil as treatments for no-reflow during PPCI can reduce all-cause mortality, non-fatal myocardial infarction or the incidence of angiographic no-reflow (TIMI flow grade < 3 and MBG 0 to1), but there was some evidence of increased adverse events. Further clinical research into adenosine and verapamil is needed because of the limited numbers of included trials and participants.
BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST segment elevation myocardial infarction. Although there is restoration of coronary flow after PPCI, impaired myocardial perfusion (known as no-reflow) is frequently observed, and is related to poor clinical outcomes. In order to overcome this phenomenon, drugs have been tried as adjunctive treatments to PPCI. Among them, verapamil and adenosine are two of the most promising drugs. There are no systematic reviews of these two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. OBJECTIVES: To study the impact of adenosine and verapamil on people with AMI who are undergoing PPCI. SEARCH METHODS: We searched the following databases in February 2012: the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, Web of Science and BIOSIS, China National Knowledge Infrastructure, Clinical Trials registers (Clinical Trials.gov, Current Controlled Trials, Australian & New Zealand Clinical Trials Registry, the WHO International Clinical Trials Registry Platform). We also handsearched the American Journal of Cardiology. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) where adenosine or verapamil was the primary intervention. Participants were individuals diagnosed with AMI who were undergoing PPCI. DATA COLLECTION AND ANALYSIS: Two review authors collected studies and extracted data. Where necessary, we contacted the trial authors to obtain the relevant information. We calculated risk ratios (RRs), P values, and 95% confidence intervals (CIs) of dichotomous data. MAIN RESULTS: We included 10 RCTs involving 939 participants in our review. Nine RCTs were associated with adenosine and one with verapamil. We considered the overall risk of bias of included studies to be moderate. There was no evidence that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.23 to 1.61, P = 0.32), long-term all-cause mortality (RR 1.20, 95% CI 0.27 to 5.22, P = 0.81), short-term non-fatal myocardial infarction (RR 1.38, 95% 0.28 to 6.96, P = 0.69) or the incidence of angiographic no-reflow (TIMI flow grade < 3 after PPCI: RR 0.72, 95% CI 0.49 to 1.07, P = 0.11, and myocardial blush grade (MBG) 0 to 1 after PPCI: RR 0.96, 95% CI 0.76 to 1.22, P=0.75). But the incidence of adverse events with adenosine, such as bradycardia (RR 6.57, 95% CI 2.94 to 14.67, P<0.00001), hypotension (RR 11.43, 95% CI 2.75 to 47.57, P=0.0008) and atrioventricular (AV) block (RR 6.67, 95% CI 1.52 to 29.21, P=0.01) was significantly increased.Meta-analysis of verapamil as treatment for no-reflow during PPCI was not calculated due to lack of data. AUTHORS' CONCLUSIONS: We found no evidence that adenosine and verapamil as treatments for no-reflow during PPCI can reduce all-cause mortality, non-fatal myocardial infarction or the incidence of angiographic no-reflow (TIMI flow grade < 3 and MBG 0 to1), but there was some evidence of increased adverse events. Further clinical research into adenosine and verapamil is needed because of the limited numbers of included trials and participants.
Authors: Sheraz A Nazir; Jamal N Khan; Islam Z Mahmoud; John P Greenwood; Daniel J Blackman; Vijay Kunadian; Martin Been; Keith R Abrams; Robert Wilcox; A A Jennifer Adgey; Gerry P McCann; Anthony H Gershlick Journal: Trials Date: 2014-09-25 Impact factor: 2.279