Acetylsalicylic acid improves outcome after acute myocardial infarction by reducing thromboinflammation.

BACKGROUND

Inflammation orchestrates an outcome after acute myocardial infarction (AMI). Thromboinflammation, via the CD40- and CD40 ligand (CD40L)-mediated platelet-leukocyte interaction, is involved in post-AMI inflammation.

OBJECTIVES

This study hypothesized that acetylsalicylic acid (ASA) exerts pleiotropic cardioprotective effects beyond prevention of reinfarction by reducing thromboinflammation and infarct size.

METHODS

A murine AMI model was used to investigate the effects of low-dose ASA, which is applied preischemia or after induction of ischemia (intraischemia), on post-AMI thromboinflammation and the outcome. To investigate the underlying mechanisms, platelet and neutrophil depletion and genetically induced and antibody-induced CD40L deficiency were applied. Thromboinflammation markers were analyzed. Translationally, the outcome after ST-elevation myocardial infarction (STEMI) was measured in ASA-pretreated vs ASA-naive patients (ClinicalTrials.gov ID: NCT03539133).

RESULTS

Both ASA treatment preischemia and intraischemia reduced infarct size and thromboinflammation and improved cardiac function and remodeling. The scar size was smaller with ASA preischemia 21 days after AMI but not with ASA intraischemia. This cardioprotection was blunted in the absence of (a) platelets or (b) neutrophils. Both pharmacologic inhibition or genetic deficiency of CD40L abrogated ASA's protective effect. Accordingly, ASA-pretreated patients with STEMI had improved outcome (12.5% vs 23.8%; hazard ratio, 0.50; 95% CI, 0.31-0.80; P < .001). This was driven by reduced mortality without differences in recurrent AMI.

CONCLUSION

Existing ASA therapy shows pleiotropic effects in the reduction of thromboinflammation and improvement of outcome after AMI, independent of its effects on the occurrence of ischemia itself. This should be considered while choosing timing of initiation and the optimal antithrombotic regime post-AMI in patients with coronary artery disease.