State of the art: Oral antiplatelet therapy

Abstract

Platelet adhesion, activation, and aggregation are central to the propagation of coronary thrombosis following rupture, fissure, or erosion of an atherosclerotic plaque. This chain of deleterious events underlies the pathophysiological process leading to an acute coronary syndrome. Therefore, oral antiplatelet therapy has become the cornerstone of therapy for the management of acute coronary syndrome and the prevention of ischemic complications associated with percutaneous coronary intervention. Landmark trials have established aspirin, and the addition of clopidogrel to aspirin, as key therapeutic agents in the context of acute coronary syndrome and percutaneous coronary intervention. Dual antiplatelet therapy has been the guideline-mandated standard of care in acute coronary syndrome and percutaneous coronary intervention. Despite the proven efficacy of dual antiplatelet therapy, adverse ischemic events continue to occur and this has stimulated the development of novel, more potent antiplatelet agents. We focus this state-of-the-art review on the most recent advances in oral antiplatelet therapy, treading the tightrope of potency versus bleeding risk, the quest to determine the optimal duration of dual antiplatelet therapy and future of personalized antiplatelet therapy.

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest

“…The maximal plasma concentration of ticagrelor was lower in MTH group vs. no-MTH group (C max for ticagrelor: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002), whereas there were no differences in maximal concentration of the metabolite between the groups (C max for AR-C124910XX: 203 ± 121 vs. 337 ± 186 ng/mL; p = 0.1). Time to achieve maximal plasma concentrations was delayed for both ticagrelor and AR-C124910XX in MTH group vs. no-MTH group (t max for ticagrelor: 12 [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] vs. 4 [2][3][4][5][6][7][8][9][10][11][12] h, p = 0.01; t max for AR-C124910XX: 18 [12][13][14][15][16][17][18][19][20][21][22][23][24] vs. 4 [4][5][6]…”

“…OHCA survivors presenting symptoms of acute MI require primary percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy (DAPT), including acetylsalicylic acid (ASA) and a P2Y 12 receptor inhibitor [1][2][3][4]. Early administration of antiplatelet agents is necessary as the highest risk of stent thrombosis was reported within the early phase after stent implantation [5]. Ticagrelor and prasugrel are the preferred P2Y 12 inhibitors in this clinical setting [6][7][8][9][10][11].…”

The influence of naloxone on pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina pectoris receiving concomitant treatment with morphine — a protocol of a randomized trial

“…Morphine has been found to intensify the muscle tone of the gastrointestinal tract, especially the sphincters, which inhibits gastric emptying and weakens intestinal peristalsis, which in turn may lead to the impairment of intestinal absorption and thus to the decrease of peak plasma levels of oral medications [8,11]. The described phenomenon, which can be called "the morphine effect" is particularly undesirable in patients treated for STEMI, as this population requires immediate platelet inhibition to increase the chance of successful therapy [12][13][14].…”

Update of Antiplatelet Therapy in Patients Without Known Cardiovascular Disease

“…Aspirin is irreversible non-selective inhibitor of cyclooxygenase enzyme (COX-1 and COX-2, respectively) that is responsible for formation of prostanoids, including prostaglandins, prostacyclins and platelet thromboxane (TxA2) (1-2). It prevents synthesis of TxA2 from arachidonic acid and therefore TxA2-induced platelet aggregation (2,16). Although efficacy and safety of aspirin in the treatment of patients without known CVD have been studied in 10 RCTs, the role of aspirin for the primary CVD prevention is still unclear (2,10,(15)(16) (17).…”

“…It prevents synthesis of TxA2 from arachidonic acid and therefore TxA2-induced platelet aggregation (2,16). Although efficacy and safety of aspirin in the treatment of patients without known CVD have been studied in 10 RCTs, the role of aspirin for the primary CVD prevention is still unclear (2,10,(15)(16) (17). The efficacy of aspirin monotherapy in reduction of CV events, especially non-fatal MI, was even higher in patients at moderate (10-20%) and high (>20%) Framingham coronary heart disease (CHD) risk, without significant reduction in stroke and CV mortality regardless of the patient CHD risk (15,18).…”