Adjunctive Intracoronary Adenosine Lessens No-Reflow in AMI Patients

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A double injection of intracoronary adenosine improves myocardial reperfusion as well as early clinical outcomes in patients receiving primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Results of the small randomized trial were published online February 11, 2011, ahead of print in the American Journal of Cardiology.

Researchers led by Marek Grygier, PhD, of the Poznan University of Medical Sciences (Poznań, Poland), randomized 70 consecutive STEMI patients at their institution to a simplified course of intracoronary adenosine or placebo during PCI. In several previous studies, adenosine has been given using complicated protocols involving infusions over prolonged periods of time. In the current study, researchers gave the drug in 2 injections by hand directly into the coronary artery through the guiding catheter both immediately after crossing the lesion (2 mg to the left or 1 mg to the right coronary artery) and immediately after the first balloon inflation (same dosing).

Baseline angiographic and clinical characteristics of the 2 groups were well matched, with the exception of an excess of smokers in the adenosine group (63% vs. 37%; P < 0.05). More patients in the adenosine group than in the placebo group had improvements in the primary endpoints of postprocedural myocardial blush grade 3 and ST-segment elevation resolution 60 minutes after PCI. Mean ejection fraction was also slightly but significantly improved with adenosine 5 to 7 days later (table 1).

Table 1. Angiographic, ECG, and Echocardiographic Endpoints

 

Adenosine
(n = 35)

Placebo
(n = 35)

P Value

MBG 3

65.7%

37.1%

< 0.05

ST Resolution

77%

43%

< 0.01

LVEF

52 ± 8%

47 ± 9%

< 0.05

Abbreviations: MBG, myocardial blush grade; LVEF, left ventricular ejection fraction.

TIMI grade 3 flow was improved with adenosine, but the difference between the adenosine and placebo groups just missed statistical significance (32% vs. 26%; P = 0.058). The same was true for the prevalence of corrected TIMI frame count (CTFC) less than 28 (32% vs. 26%; P = 0.057). CTFC 28 to 40, meanwhile, was similar in both groups, while CTFC greater than 40 was less common with adenosine (0 vs. 4%; P < 0.05).

Peak levels of creatine kinase (CK), CK-MB, and troponin were similar between the 2 groups.

In terms of clinical outcomes, the composite of death, MI, cardiac arrest, cardiogenic shock, heart failure, and recurrent angina was lower in the adenosine group at 1 month (8.6% vs. 31.4%; P < 0.05). There were no deaths or recurrent MIs in the entire cohort. Other individual clinical outcomes were consistently lower in the adenosine group, though the differences were not statistically significant (table 2).

Table 2. Individual Clinical Endpointsa

 

Adenosine
(n = 35)

Placebo
(n = 35)

Cardiac Arrest

5.7%

11.4%

Heart Failure > NYHA Class II

5.7%

14.3%

Angina Leading to Repeat Angiography

2.9%

11.4%

a P = NS for all comparisons.

“The main finding of our study was that the new, simple protocol of adenosine injections through the guiding catheter was effective in improving myocardial perfusion and preventing the no-reflow phenomenon,” the researchers conclude.

Standard Care of the Future?

“I believe that if our results can be confirmed by larger trials, intracoronary adenosine should become standard care in the primary PCI setting. Our protocol of adenosine administration is simple, cheap, and easy to use everywhere,” Dr. Grygier told TCTMD in an e-mail communication. “Moreover, adenosine administration improves angiographic and electrocardiographic results in patients with acute myocardial infarction with ST-segment elevation undergoing percutaneous coronary intervention. Adenosine administration seems to be associated with a more favorable clinical course. However, we definitely need larger trials.”

He acknowledged that the exact cardioprotective mechanism of adenosine is not fully understood, noting that neutrophil activation and prevention of endothelial damage seem to play a major role. “Moreover, adenosine antagonizes many of the biochemical and physiological mechanisms implicated in ischemia-reperfusion injury and has been shown to reduce post-ischemic ventricular dysfunction and myocyte necrosis and apoptosis,” Dr. Grygier said.

The actual keys to the technique’s success, he added, are both the timing—immediately after guidewire crossing and after the first low-pressure balloon inflation—and the relatively high dose of the adenosine injections.

Nothing New Here

However, not everyone was as impressed with the results. In an e-mail communication with TCTMD, Gennaro Sardella, MD, of “Sapienza” University of Rome (Rome, Italy), called the trial “not really new except for the method of adenosine infusion. In my experience and that of many others, adenosine has resulted in safety and efficacy during primary PCI.”

Dr. Sardella presented results in May 2010 at EuroPCR in Paris, France, from the RACE (Randomized comparison of Adenosine intracoronary infusion and Clopidogrel pretreatment on myonecrosis occurrence in Elective PCI) trial demonstrating the benefits of adenosine in patients who are not given or do not respond to clopidogrel before elective PCI.

He indicated being unsurprised that the control group in the current study fared worse, especially since few patients received glycoprotein IIb/IIIa inhibitors and none received thrombectomy. “The real comparison should be made between the double adenosine infusion and a treated control group,” Dr. Sardella said.

In the paper, the authors acknowledge that “the study protocol was designed before the era of widespread use of thrombectomy during primary PCI. It would be interesting to determine whether our results would be reproducible during PCI with the combination of adenosine injections and balloon thrombectomy.”

Still, Dr. Sardella supports using adenosine during primary PCI. “Adenosine infusion can fit with any other intervention,” he said. “In my experience, we usually use adjunct adenosine infusion with thrombectomy and GP IIb/IIIa inhibitors.”

Along similar lines, Dr. Grygier offered a basic recommendation to clinicians: “Try intracoronary adenosine with your next AMI patient undergoing primary PCI.”

Study Details

The injections of adenosine or saline directly to the coronary arteries were well tolerated and were not associated with significant side effects. No patient complained of worsening chest pain or developed hemodynamic instability. Significant bradyarrhythmias, including asystole and third-degree atrioventricular block, were observed in 8 patients, occurring only after adenosine injection to the RCA. These episodes lasted for a few seconds (maximum of 15 seconds), resolved spontaneously or after the patient coughed, and did not require temporary pacing in any patient.

 


Source:
Grygier M, Araszkiewicz A, Lesiak M, et al. New method of intracoronary adenosine injection to prevent microvascular reperfusion injury in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Am J Cardiol. 2011;Epub ahead of print.

 

 

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Disclosures
  • Dr. Grygier made no statement regarding conflicts of interest.
  • Dr. Sardella reports no relevant conflicts of interest.

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