Left ventricular function and cardiovascular events following adjuvant therapy with adenosine in acute myocardial infarction treated with thrombolysis, results of the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study.
BACKGROUND
Reperfusion therapy for acute myocardial infarction (AMI) reduces mortality but is also associated with reperfusion injury. The present study tested the hypothesis that adjuvant therapy with a low anti-inflammatory dose of adenosine might prevent reperfusion injury and preserve left ventricular function.


METHODS
Six hundred and eight patients with ST-elevation AMI were randomised to receive infusions of adenosine (10 microg x kg(-1) x min(-1)) or placebo (saline) to be started with thrombolysis and maintained for 6 h. The primary endpoint was global and regional left ventricular systolic and diastolic function, as assessed by two-dimensional and Doppler echocardiography before hospital discharge. The secondary end-point was all cause and cardiovascular mortality, and non-fatal myocardial infarction during 12 months of follow-up.


RESULTS
No beneficial effect of adenosine was found regarding echocardiographic indices of left ventricular systolic or diastolic function. Recruitment was stopped due to this apparent lack of effect after an interim analysis. However, after 12 months of follow-up, cardiovascular mortality was 8.9% with adenosine and 12.1% with placebo treatment [odds ratio (OR) 0.71, 95% confidence interval (C.I.) 0.4-1.2, P=0.2] among all patients and 8.4% vs 14.6% (OR 0.53, 95% C.I. 0.23-1.24, P=0.09) among patients with anterior AMI. All cause mortality differed similarly. Non-fatal AMI was not reduced similarly by adenosine treatment. Survival curves indicate that possible survival benefits are maintained after the first year of follow-up.


CONCLUSIONS
Adenosine, given as adjunctive treatment with thrombolysis, did not provide detectable improvement of echocardiographic indices of left ventricular function when assessed before hospital discharge. Cardiovascular and all cause mortality appear to have been reduced by low-dose adenosine treatment, and the size of the effect appears to be clinically relevant (absolute risk reductions of approximately 4%). The power of the study regarding morbidity and mortality was, however, limited. The results are compatible with a beneficial anti-inflammatory effect of adenosine treatment on reperfusion injury after thrombolysis, which may be mediated by inhibition of leukocytes in peripheral blood. A larger trial is warranted to possibly establish beneficial effects of low-dose adenosine on survival after thrombolysis.
The Karolinska Institute at the Department of Cardiology, Huddinge University Hospital, 141 86 Huddinge, Stockholm, Sweden. miguel.quintana@labtek.ki.se
Miguel
M
Quintana
Paul
P
Hjemdahl
Alf
A
Sollevi
Thomas
T
Kahan
Magnus
M
Edner
Nina
N
Rehnqvist
Eva
E
Swahn
Ann-Catrin
AC
Kjerr
Per
P
Näsman
D000241:Adenosine / Q000009:adverse effects / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control*
D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D000241:Adenosine