Stronger inhibitory effects of Ticagrelor plus aspirin compared with Clopidogrel plus aspirin on arachidonic acid-induced platelet aggregation in patients with acute coronary syndrome with PCI.

Antagonists of the Adenosine Diphosphate (ADP) receptor, P2Y12, may inhibit platelet aggregation as a result of stimulation with arachidonic acid (AA). The potent P2Y12 blocker, Ticagrelor has greater anti-platelet effects than Clopidogrel. We explored the effects of Ticagrelor versus Clopidogrel on mean maximum aggregation ratios (MAR%) in response to AA stimulation in patients receiving aspirin in conventional doses. A total of 613 acute coronary syndrome (ACS) patients were followed from October 2017 to October 2018. At the one- and six-month follow-up visit, mean AA-MAR% was lower in the Ticagrelor group when compared with the Clopidogrel group (28.9% vs 31.7%, 28.4% vs 31.0%, p<0.001 and p=0.001, respectively). BARC1-2 bleeding occurred with greater frequency with Ticagrelor than in patients treated with Clopidogrel (29.3% vs 9.5%, p<0.001; 23.5% vs 9.3%, p<0.001). Excessive platelet inhibition and decreased AA-MAR% were considered the main reasons for the severe subcutaneous/dermal bleeding in Ticagrelor treated patients.

Anti-thrombotic strategies in patients with atrial fibrillation undergoing PCI.

Triple anti-thrombotic therapy combining oral anticoagulation and dual anti-platelet therapy following percutaneous coronary intervention in patients with atrial fibrillation was considered as standard and recommended by guidelines. While bleeding risk is considerable with that approach, data for efficacy are scare. Several trials assessed the possibility of reducing anti-thrombotic treatment by mainly shortening the exposure to acetylsalicylic acid. Dropping one of the anti-platelet components might increase the risk of stent thrombosis, myocardial infarction or stroke. Despite that fear, the recent trials' primary endpoint was major and/or clinically-relevant non-major bleeding. We review data on major bleedings, intracranial bleedings and major adverse cardiovascular events from the published reports. We demonstrate that Non-Vitamin K oral anticoagulant (NOAC)-based strategies compared to VKA-based triple therapies significantly reduce the risk for TIMI-major bleedings by 39% and for intracranial bleedings by 66%, while they did not increase the risk for overall ischemic or embolic events. However, recent meta-analyses indicate an increased risk for stent thrombosis with less intense anti-thrombotic therapy. While the overall incidence rate for stent thrombosis is rather low, relative increases by about 30-60% are reported, but they did not translate into adverse clinical net-benefit ratios. This review highlights that using certain NOAC regimens proven effective for stroke prevention in AF can reduce the rate of bleeding without increasing ischemic or embolic events. Furthermore, additive ASA in triple anti-thrombotic regimens should be limited to 1 month and individual weighing of ischemic versus bleeding risk during the first 30 days seems to be reasonable.

Anti-thrombotic strategies in elderly patients receiving platelet inhibitors.

Acetyl-salicylic acid is the basic anti-thrombotic therapy used for single anti-platelet therapy in primary as well as secondary prevention of atherosclerotic disease. Dual anti-platelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary intervention or acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). DAPT duration has been frequently discussed. Currently, guideline recommendations strengthen the importance of individualized treatment to reduce bleeding risk based on clinical predictors, of which older age is an important one. Patients aged ≥75 years are often underrepresented in randomized clinical trials, but present a patient cohort deemed both at heightened ischaemic as well as bleeding risk. We aimed to summarize the evidence or the lack of evidence for anti-platelet treatment strategies in patients aged ≥75 years including combinations with anticoagulants in secondary prevention or coronary interventions in elderly patients with atrial fibrillation. This review article represents the author's interpretation of available data and is not discussed by a formal task force; it is intended to point out missing evidence and to provide age-specific data for individualized decision making, which is currently encouraged by the guidelines.

[Platelet inhibition in elderly patients]. / Thrombozytenhemmung beim alten Menschen.

Single antiplatelet therapy (SAPT) using predominantly acetylsalicylic acid (ASA) is the baseline anti-thrombotic therapy in primary as well as secondary prevention of atherosclerotic disease. Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary interventions or acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina pectoris). In the past the duration of DAPT in particular has been frequently discussed. Current recommendations, such as the "Focused Update DAPT 2017" of the European Society of Cardiology (ESC) emphasize the importance of strategies aiming to reduce an increased risk of bleeding based on clinical predictors. In this case older age is an important factor relevant for bleeding. In this article, the evidence for SAPT or DAPT is summarized with a special focus on patients aged ≥75 years.

Platelet inhibition during ticagrelor monotherapy versus ticagrelor plus aspirin in patients with coronary artery disease (TEMPLATE study): study protocol for a randomised controlled trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin (ASP) and a P2Y12 blocker is currently standard care after percutaneous coronary intervention (PCI) with stent insertion, and aims to inhibit platelet function in order to prevent stent thrombosis. The P2Y12 blocker ticagrelor (TIC) has greater antiplatelet effect than the previously used members of this class, such as clopidogrel. In healthy volunteers, TIC is sufficient to cause strong platelet inhibition, with little additional effect from ASP. Omission of ASP may improve the safety of antiplatelet regimes by reducing bleeding. However, the effect of single antiplatelet treatment with TIC, compared to DAPT with TIC + ASP, has not been studied in detail in patients with coronary artery disease. METHODS: To compare TIC with TIC + ASP, we have initiated a single centre, open-label randomised controlled trial (TEMPLATE study) in adults receiving DAPT following PCI with a sample size of 110 patients. Patients are invited to join the study when, as part of standard care, they are due to switch from DAPT (ASP + any P2Y12 blocker) to single antiplatelet treatment with ASP alone after 6-12 months. Patients are randomised to receive either TIC or TIC + ASP for 4 weeks. All patients then revert to standard care with ASP alone. Blood samples and clinical data are collected at three study visits: at baseline during treatment with ASP + any P2Y12 blocker (visit 1); approximately 4 weeks after visit 1 during treatment with either TIC or TIC + ASP (visit 2); and approximately 8 weeks after visit 1 when treatment has reverted to ASP alone (visit 3). The primary outcome is the extent of platelet inhibition, measured by light transmission aggregation, flow cytometry, flow chamber and plasma biomarker tests. The primary analysis will compare the extent of platelet inhibition between the TIC and TIC + ASP groups at visit 2, adjusted for baseline platelet reactivity. Secondary analyses will compare the extent of platelet inhibition at visit 2 with that at visit 3. DISCUSSION: This is the first study to compare in detail the extent of platelet inhibition in patients who are receiving TIC compared with TIC + ASP. The study findings will complement larger-scale trials of the clinical efficacy and safety of TIC compared to TIC + ASP. TRIAL REGISTRATION: ISRCTN registry, identifier ISRCTN84335288 . Registered on 23 June 2014.

[Focused update on dual antiplatelet treatment : ESC guidelines 2017]. / Fokussiertes Update zur dualen Plättchenhemmung : ESC-Leitlinie 2017.

Dual antiplatelet treatment (DAPT) is a cornerstone of maintenance medication of patients following elective percutaneous coronary interventions or an acute coronary syndrome (ACS), e. g. ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina. In recent years the inclusion of P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. Following the introduction of the modern generation of drug-eluting stents for elective coronary interventions, the duration of the necessary DAPT has been clearly reduced. In patients with ACS the question arises when treatment with one of the more potent P2Y12 inhibitors, such as prasugrel and ticagrelor should be used instead of clopidogrel. A potential extension of DAPT beyond 12 months can be considered in high-risk patients after implantation of bioresorbable vascular scaffolds and following myocardial infarction. A special focus is on those patients who have already been treated with oral anticoagulants for stroke prevention in atrial fibrillation and require additional platelet inhibition following coronary stenting. This article summarizes and assesses the major recommendations given in the Focused Update DAPT 2017 of the European Society of Cardiology (ESC). In particular the recommendations address strategies to reduce an increased risk of bleeding based on clinical predictors.