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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 µg·kg-1·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 ≈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. [ABSTRACT FROM AUTHOR]

In addition to clinical risk markers, indices of left ventricular (LV) systolic function are valuable prognostic markers after acute myocardial infarction (MI). Previous studies have also suggested that LV diastolic function may contribute with prognostic information. The present study assessed whether this assumption applies to a large population of patients with acute MI who underwent thrombolytic therapy.520 out of 608 patients participating in the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study, with an ST-elevation acute MI underwent two-dimensional and Doppler echocardiographic examination at 4 (range 2–10) days after admission. During the follow-up period of 31 (S.D.±11) months, cardiovascular death occurred in 57 (11%) patients, nonfatal acute MI occurred in 77 (15%), and 124 (24%) patients suffered a combined cardiovascular end-point (either nonfatal acute MI or cardiovascular death). Univariate regression analysis showed that all indices of LV systolic function predicted cardiovascular death and combined cardiovascular end-points. Regarding LV diastolic function only a restrictive filling pattern predicted cardiovascular death. In a multistep multivariate regression analysis in which the variables were introduced in a hierarchic order age, history of systemic hypertension, wall motion score index (WMSi), and history of previous MI and diabetes mellitus were independent predictors of cardiovascular death. A history of systemic hypertension or congestive heart failure were independent predictors of nonfatal acute MI, while a history of systemic hypertension, wall motion score index and diabetes mellitus independently predicted combined cardiovascular end-points.The results of this study confirmed that clinical risk indicators and LV systolic function were the most important independent predictors of cardiovascular death and combined cardiovascular end-points. LV diastolic function assessed by Doppler-echocardiography did not provide additional prognostic information. [Copyright &y& Elsevier]