Cangrelor in patients with percutaneous coronary intervention for acute myocardial infarction after cardiac arrest and/or with cardiogenic shock

Abstract

The highest mortality in patients undergoing percutaneous coronary intervention (PCI) is observed in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), cardiac arrest (CA) or with the need for mechanical ventilation. It has been shown that the onset of action of oral P2Y12 inhibitors is delayed in patients with CS or after CA, especially in those with therapeutic hypothermia and administration of morphine, which is associated with a high incidence of stent thrombosis.1 Cangrelor is administered intravenously and binds directly at the P2Y12 receptor and thus inhibits Adenodiphosphat (ADP)-induced platelet aggregation within minutes in a complete and rapidly reversible fashion.2 We have performed a retrospective study to assess the use of cangrelor in high-risk patients with acute myocardial infarction (AMI) in a real-world population in Austria and Germany. The methods are given in the Supplementary material. All patients underwent PCI for AMI and presented with heart failure with the need for ventilation (n = 10, 3.3%), CA before PCI (n = 148, 48.8%), CS (n = 42, 13.9%), or CA and CS (n = 103, 34.0%). Baseline characteristics and results of the total population and the four subgroups are given in Table 1. Oral P2Y12 inhibitors used were clopidogrel in 27.8%, prasugrel in 38.0%, and ticagrelor in 36.0%, respectively. The cangrelor infusion was started before PCI in 12.9% of cases and administered for a mean duration of 121.2 ± 53.5 min. The majority of patients (67.4%) was treated for <2 h, 25.3% for 2–4 h, and 7.3% for >4 h. The primary outcome of stent thrombosis and myocardial re-infarction within the first 48 h was reported in two (0.7%) patients. Bleeding Academic Research Consortium (BARC) 2–3 bleeding complications were observed in 11.2% of patients and fatal bleedings (BARC 5) in 3.3%. Total in-hospital mortality was 41.6%, and cardiac mortality was 21.8%. In the matched comparison analysis of 118 patients in each group, comparable Thrombolysis in myocardial infarction (TIMI) 3 patency rates of the infarct-related artery (IRA) after PCI (91.5% vs. 87.9%) and numerically fewer ischaemic events were observed compared with the patients in the CULPRIT-SHOCK trial3 (Figure 1). To the best of our knowledge, this is one of the largest studies evaluating the use of cangrelor in very high-risk patients with AMI undergoing PCI. The results can be summarized as follows: cangrelor is associated with a low rate of stent thrombosis and re-infarction within the first 48 h after PCI; the number of ischaemic and bleeding events and total and cardiac mortality were numerically lower compared with those in a matched patient group of patients with CS from the CULPRIT-SHOCK trial. Comparison of in-hospital events in a matched comparison between 118 patients included in the CAN-SHOCK trial treated with cangrelor and 118 patients included in the CULPRIT-SHOCK trial treated with oral P2Y12 inhibitors. Combined endpoint: death, stent thrombosis, re-myocardial infarction, stroke, and BARC 2–5 bleeding. Baseline parameters and results of the total population and in the four groups according to the initial clinical status Abbreviation: CV, Cardiovascular. Our results support the findings of the CANGRELOR-OHCA study,2 which suggest that cangrelor is able to prevent ischaemic complications in the early hours after PCI in CA patients, even more effective than with oral P2Y12 inhibitors. Bleeding complications occurring in ∼15% were reported in more than half of cases after more than 24 h and therefore might be not directly associated with the use of cangrelor. Thus, cangrelor seems to provide an acceptable safety profile after CA, supporting the recommendation for the use of cangrelor for PCI after CA in a position statement of the European Association for Percutaneous Coronary Intervention (EAPCI).4 There are limited data available evaluating the clinical profile of cangrelor in the context of CS. A multicentre study has shown5 a trend towards an improved outcome in a matched-pair analysis of patients treated with cangrelor compared with patients included in the IABP-SHOCK 2 study. The ongoing randomized Dual Antiplatelet Therapy for Shock Patients with Acute Myocardial Infarction trial will determine the role of cangrelor in PCI for CS. Our study is subject to a number of limitations. Given the non-randomized design and potential for selection bias, these findings should be regarded as hypothesis-generating. Since we did not have autopsies and mandatory control coronary angiography available, the rate of stent thrombosis might be higher than observed clinically. Supplementary material is available at European Heart Journal: Acute Cardiovascular Care. The CAN-SHOCK study has been supported by an unrestricted grant from Ferrer, Germany. The data underlying this article cannot be shared publicly due to data protection issues. The data will be shared on reasonable request to the corresponding author.

Topics & Concepts