The balance of thrombosis and hemorrhage in STEMI patients with or without associated cardiac arrest: An observational study

Abstract

Background

Data is scarce on hemorrhagic and thrombotic complications in patients with ST-elevation myocardial infarction (STEMI) associated with out-of-hospital cardiac arrest (OHCA).

Methods

This is a monocentric, retrospective study conducted from January 2012 to December 2017 in a tertiary university hospital, which serves as a cardiac arrest center for a large urban area. Over the study period, all consecutive patients who were treated with stent implantation for STEMI with or without OHCA were included. Baseline characteristics, treatments, hemorrhagic and thrombotic events were compared between STEMI patients with and without OHCA. Univariate and multivariate analysis were performed in order to identify predictors of 30-day mortality, occurrence of major bleeding (MB), and early stent thrombosis (ST).

Results

A total of 549 patients treated for STEMI without OHCA and 146 patients for STEMI with OHCA were included. The incidence of definite ST and MB after coronary angioplasty was significantly higher in patients with OHCA (2.6% vs. 7.5%, p = 0.004 and 3.3% vs. 19.2%, p < 0.001, respectively). Independent predictors of MB in OHCA patients were anticoagulation therapy (HR = 3.11, 95%CI [1.22–7.98], p = 0.02) and the use of glycoprotein IIb/IIIa inhibitors (HR = 4.16, 95%CI [1.61–10.79], p = 0.003). Independent predictors of mortality in OHCA patients were age (HR = 1.05, 95%CI [1.02–1.09], p = 0.004) and ST (HR = 5.62, 95%CI [1.61–19.65], p = 0.007, with a protective effect of new anti-P2Y12 treatments (HR = 0.20, 95%CI [0.08-0.46], p < 0.001).

Conclusion

Patients treated for STEMI associated with OHCA are at higher-risk of ST and MB than those who did not experience cardiac arrest. In this subset of patients, prospective studies are needed to better evaluate the balance of thrombosis and hemorrhage.

Introduction

Acute coronary syndromes (ACS) are the leading cause of sudden cardiac arrest in adults.¹ European guidelines recommend urgent coronary angiography in a view for primary percutaneous coronary intervention (PCI) in survivors of out-of-hospital cardiac arrest (OHCA).1, 2 This primary PCI strategy is particularly recommended in patients with resuscitated cardiac arrest and an ECG consistent with ST segment elevation myocardial infarction (STEMI) (Class I), but urgent angiography (and PCI if indicated) should also be considered in those without diagnostic ST-segment elevation but with a high suspicion of ongoing myocardial ischemia (Class IIa).³ Data concerning thrombotic events in these OHCA patients are controversial. Shock, hypothermia and changes in antiplatelet pharmacokinetic have been pointed at as potential promoters of stent thrombosis (ST). Indeed, hypothermia used to prevent ischemia-related organ damage has been showed to be associated with pro-thrombotic side effects in pre-clinical studies. Different mechanisms such as increased expression of platelet activation marker P-selectin, platelet-leukocyte aggregate formation, and thrombocytopenia were described.⁴ When comparing ST in patients with acute myocardial infarction and OHCA, Joffre et al. found a significantly higher incidence of confirmed acute or subacute ST in the cardiac-arrest group treated with cooling than in the control group (10.9% vs. 2.0%, p = 0.01).⁵ On the other side, OHCA patients are also at higher risk of bleeding events, that may be promoted by cardio-pulmonary resuscitation maneuvers and subsequent trauma induced by chest compressions used for resuscitation, by antithrombotic therapies associated with coronary angiography and subsequent angioplasty (i.e., antiplatelet therapy, heparin, and Glycoprotein IIb/IIa-inhibitors), by the need of arterial and venous lines insertion at the initial phase of intensive care, and by potential need of large mechanical support devices such as Impella or Extra-corporeal membrane oxygenation.⁶ There is an activation of the inflammatory reaction associated with clinical features that are very similar to those observed during severe sepsis. Coagulation abnormalities have been identified, involving a significant activation of coagulation factors, whereas endogenous anticoagulants (antithrombin, protein S and C) are decreased. This intravascular coagulation can be implicated in the genesis of microvascular abnormalities, which in turn lead to more visceral lesions. Of note these coagulation abnormalities are particularly common in patients who die quickly from a post-resuscitation shock.⁷ Lastly, cardiac arrest patients treated with hypothermia experience increased platelet aggregation and strengthened clot formation over time. In addition, in patients on oral dual platelet inhibition, the effect of ticagrelor is delayed, probably due to slow gastric emptying,⁸ Indeed, the effect of platelet inhibition with the P2Y12-antagonist pro-drug clopidogrel may vary secondary to differences in intestinal absorption, variations in liver cytochrome activities, drug interactions, and platelet receptor polymorphisms.⁹ Although thrombotic/hemorrhagic balance is starting to be well documented in ACS without cardiac arrest,¹⁰ data is scarce concerning patients presenting STEMI associated with OHCA, two populations that share the same trigger but seem to be fundamentally different in regard of thrombotic/hemorrhagic balance. Therefore, using an observational retrospective study we sought to evaluate the thrombotic/hemorrhagic balance in patients with STEMI associated or not with OHCA.