Impact of the New P2Y12 Receptor Inhibitors on Mortality in STElevation Myocardial Infarction Patients with Cardiogenic Shock and / or After Cardiopulmonary Resuscitation Undergoing Percutaneous Coronary Intervention

Abstract

IntroductionST-Elevation Myocardial Infarction (STEMI) represents a highly pro-thrombotic state with platelets being greatly activated [1,2]. The early and strong platelet inhibition seems to be of paramount importance in patients with STEMI undergoing Percutaneous Coronary Intervention (PCI) [3]. Newer P2Y12 receptor inhibitors prasugrel and ticagrelor (newer P2Y12) exhibit more rapid, potent, and consistent platelet inhibition than clopidogrel and reduce the risk for ischemic cardiovascular complications [4][5][6][7][8][9][10]. In STEMI patients, an initial delay in the onset of newer P2Y12 antiplatelet action was observed and ticagrelor did not appear superior to prasugrel [3]. However, patients with Cardiogenic Shock (CS) or after Cardio Pulmonary Resuscitation (CPR) were mostly excluded from randomized studies and data on the clinical efficacy of these drugs comparing to clopidogrel in these patients is sparse [11][12][13].CS has a profound effect on drug absorption and metabolism due to the disturbance of microcirculation, the use of catecholamines and opioids which results in slower platelet inhibition [13][14][15]. The pharmacological properties of the newer P2Y12 are promising in a CS setting since their bioactivation is more rapid and consistent when compared to clopidogrel [2,13].Mild therapeutic hypothermia leads to a pro-thrombotic milieu per se and activation of the P2Y12 receptor inhibitors (P2Y12) may AbstractBackground: Little is known about clinical efficacy of newer P2Y12 receptor inhibitors in ST-elevation myocardial infarction patients presenting with cardiogenic shock or after cardiopulmonary resuscitation. The aim of our study was to establish the possible role of newer P2Y12 receptor inhibitors prasugrel and ticagrelor on survival in comparison to clopidogrel administration in ST-elevation myocardial infarction patients presenting with cardiogenic shock and / or after cardiopulmonary resuscitation.

Clopidogrel, ticagrelor, prasugrel or an alternation of two P2Y12 in patients with acute myocardial infarction with cardiogenic shock

“…The percentage of patients receiving a combination of P2Y12 in our analysis (9.7%) was comparable to the pooled analysis of two randomized controlled prospective trials (13.1%) ( 2 ). Results of previous analyzes are inconclusive and sometimes contradictory ( 2 , 3 , 9 , 11 , 19 – 21 ). Retrospective analyzes and pooled data showed superiority of potent P2Y12 ( 3 , 12 , 9 ), whereas prospective and some retrospective studies showed no difference in survival between P2Y12 ( 2 , 11 , 19 – 21 ).…”

“…In patients with CS, multiple challenges with antiplatelet action remain ( 9 ). The antiplatelet effect of orally administered drugs is delayed by gastroparesis, delayed intestinal absorption, and slower metabolism of the drugs due to compromised hemodynamics in cardiogenic shock, and after morphine administration ( 3 , 5 – 7 , 10 ). In addition, oral administration of the drugs may be problematic ( 9 ).…”

“…In addition, oral administration of the drugs may be problematic ( 9 ). The data on P2Y12 receptor antagonists (P2Y12) in patients with CS are sparse and still inconclusive ( 2 , 3 , 9 ). The combined results of two randomized trials showed that there is no difference between the P2Y12 ( 2 ) while pooled analysis of randomized and retrospective studies showed a better outcome with potent P2Y12 ( 3 , 9 ).…”

“…The data on bleeding are also controversial and inconclusive ( 9 ). Some have found no difference in bleeding ( 3 , 9 , 11 , 12 ), whereas others have found a lower risk of bleeding with ticagrelor and a similar risk with prasugrel compared with clopidogrel ( 2 ). Randomized trials have numerous exclusion criteria and do not always capture the actual problems of individual patients.…”

“…Potent P2Y12 are usually later switched to clopidogrel in combination with oral anticoagulants. The combination of P2Y12 in the acute setting, when heparin/bivalirudin and GP IIb/IIIa receptor antagonists are also used, is expected to be associated with bleeding, a known predictor of worse outcome ( 1 , 3 ). These patients have mostly been excluded from randomized trials or have not been evaluated separately, and there are no data on how the combination of oral P2Y12 receptor antagonists affects bleeding and outcome in patients with CS, in whom drug administration, absorption, metabolism, and efficacy differ from other patients with MI.…”