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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

  • Clinical Trials
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

The authors wish to thank all investigators who enthusiastically contributed to this study (see Appendix). We are very grateful for the support of Item Development AB, who sponsored meetings and data analysis, and provided adenosine and placebo for the study. Further support was obtained by grants from the Karolinska Institute, the Swedish Heart-Lung Foundation, the Swedish Society of Medicine and the Swedish Medical Research Council (project no. 7485).

Author information

Authors and Affiliations

  1. The Karolinska Institute at the Department of Cardiology, Huddinge University Hospital, 141 86 Huddinge, Stockholm, Sweden

    Miguel Quintana

  2. The Karolinska Institute at the Department of Clinical Physiology, Huddinge University Hospital, Stockholm, Sweden

    Miguel Quintana

  3. Department of Anesthesiology, Huddinge University Hospital, Stockholm, Sweden

    Alf Sollevi

  4. Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden

    Paul Hjemdahl

  5. Division of Internal Medicine, Danderyd Hospital, Stockholm, Sweden

    Thomas Kahan, Magnus Edner, Nina Rehnqvist & Ann-Catrin Kjerr

  6. National Board of Health and Welfare, Stockholm, Sweden

    Nina Rehnqvist

  7. Department of Cardiology, Linköping University Hospital, Stockholm, Sweden

    Eva Swahn

  8. Royal Institute of Technology, Stockholm, Sweden

    Per Näsman

Authors
  1. Miguel Quintana
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  2. Paul Hjemdahl
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  3. Alf Sollevi
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  4. Thomas Kahan
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  5. Magnus Edner
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  6. Nina Rehnqvist
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  7. Eva Swahn
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  8. Ann-Catrin Kjerr
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  9. Per Näsman
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Consortia

for the ATTACC investigators

Corresponding author

Correspondence to Miguel Quintana.

Appendix

Appendix

The ATTACC study had the following organisation and participating investigators:

  • Principal Investigators: N. Rehnqvist, P. Hjemdahl, A. Sollevi.

  • Participating centres and investigators: Danderyd University Hospital, Stockholm: T. Kahan, M. Edner, P. Hansson, M. Quintana; Linköping University Hospital: E. Swahn, R.M. Pettersson, M. Gustafsson; Helsingborg Hospital: O. Fredholm, L. Ljungdahl; Central Hospital, Skövde: A. Kallryd. County Hospital, Halmstad: A. Kirkegaard, G. Ruter.

  • Echocardiography Core Laboratory: Cardiovascular Research Laboratory, Karolinska Institutet Danderyd Hospital. M. Edner, M. Quintana, A.-C. Kjerr.

  • Safety Committee: P. Näsman, A. Sjögren, O. Nyqvist.

  • Statistical analysis: P. Näsman, M. Quintana

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Quintana, M., Hjemdahl, P., Sollevi, A. et al. Left ventricular function and cardiovascular events following adjuvant therapy with adenosine in acute myocardial infarction treated with thrombolysis. Eur J Clin Pharmacol 59, 1–9 (2003). https://doi.org/10.1007/s00228-003-0564-8

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  • DOI: https://doi.org/10.1007/s00228-003-0564-8

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