Drugs used as add-on therapy to heart procedure following heart attack

Acute myocardial infarction (AMI), or heart attack, is one of the major causes of mortality worldwide. Approximately one-third of people suffering heart attacks die before they reach the hospital. Primary percutaneous coronary intervention (PPCI) is a procedure whereby the coronary artery is widened without surgery, using a stent. Although this procedure restores blood flow through the coronary artery, perfusion through all areas of the heart may not occur. This is known as no-reflow. To try to resolve this problem, healthcare workers have tried drugs such as adenosine and verapamil as add-on treatment. We include 11 studies in this review with a total of 1027 participants. Ten studies compared adenosine or placebo as an addition to PPCI, and one compared verapamil or placebo.

No evidence suggests that adenosine reduced short-term or long-term all-cause mortality or non-fatal myocardial infarction to a greater extent than placebo treatment. However, we found evidence to show that adenosine can decrease angiographic no-reflow after PPCI. Conversely, we also found evidence indicating that adverse events (bradycardia, hypotension, atrioventricular block) were increased with adenosine, although these effects were short-lived. Included studies were few, with low numbers of participants and a relatively short period of follow-up, and event rates of mortality and angiographic no-reflow were low. Our meta-analyses therefore had insufficient numbers to support a clear-cut conclusion about the impact of adenosine in people with AMI undergoing PPCI.

Authors' conclusions: 

It is difficult to draw conclusions because of the insufficient quality and quantity of current research studies. We considered the overall risk of bias of included studies to be moderate. Adenosine as treatment for no-reflow during PPCI could reduce angiographic no-reflow (TIMI flow grade < 3) but was found to increase adverse events. What's more, no evidence could be found to suggest that adenosine reduced all-cause mortality, non-fatal myocardial infarction or the incidence of myocardial blush grade 0 to 1. Additionally, the efficacy of verapamil for no-reflow during PPCI could not be analysed because data were insufficient. Further clinical research into adenosine and verapamil is needed because of the limited numbers of available trials and participants.

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Background: 

Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST-segment elevation myocardial infarction. Although coronary flow is restored after PPCI, impaired myocardial perfusion (known as no-reflow) related to poor clinical outcomes is frequently observed. To overcome this phenomenon, drugs, such as atorvastatin, abciximab and others, have been tried as adjunctive treatment to PPCI. Among these drugs, verapamil and adenosine are among the most promising. No other systematic reviews have examined use of these two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. This is an update of the version previously published (2013, Issue 6), for which the people of interest in the review were those treated with PPCI - not those given fibrinolytic therapy.

Objectives: 

To study the impact of adenosine and verapamil on no-reflow during PPCI in people with AMI.

Search strategy: 

We updated searches of the following databases in June 2014 without language restriction: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science and BIOSIS, China National Knowledge Infrastructure and clinical trials registers (ClinicalTrials.gov, Current Controlled Trials, Australian and New Zealand Clinical Trials Registry, the World Health Organization (WHO) International Clinical Trials Registry Platform). We also handsearched The American Journal of Cardiology.

Selection criteria: 

We selected randomised controlled trials (RCTs) in which 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. When necessary, we contacted trial authors to obtain relevant information. We calculated risk ratios (RRs), P values and 95% confidence intervals (CIs) of dichotomous data.

Main results: 

We included in our review 11 RCTs (one new study with 59 participants) involving 1027 participants. Ten RCTs were associated with adenosine and one with verapamil. We considered the overall risk of bias of included studies to be moderate. We found no evidence that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.25 to 1.48, P value = 0.27), long-term all-cause mortality (RR 0.78, 95% CI 0.22 to 2.74, P value = 0.70), short-term non-fatal myocardial infarction (RR 1.32, 95% 0.33 to 5.29, P value = 0.69) or myocardial blush grade (MBG) 0 to 1 after PPCI (RR 0.96, 95% CI 0.76 to 1.22, P value = 0.75). The incidence of thrombolysis in myocardial infarction (TIMI) flow grade < 3 after PPCI (RR 0.62, 95% CI 0.42 to 0.91, P value = 0.01) was decreased. Conversely, adverse events with adenosine, such as bradycardia (RR 6.32, 95% CI 2.98 to 13.41, P value < 0.00001), hypotension (RR 11.43, 95% CI 2.75 to 47.57, P value = 0.0008) and atrioventricular (AV) block (RR 6.78, 95% CI 2.15 to 21.38, P value = 0.001), were significantly increased.

Meta-analysis of verapamil as treatment for no-reflow during PPCI was not performed because data were insufficient.

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