Platelet P2Y12 Receptor Inhibitors Research Articles

Review of the Ticagrelor Trials Evidence Base.

Ticagrelor is a platelet P2Y12 receptor inhibitor approved for use in patients with acute coronary syndromes, coronary artery disease, and low-moderate risk acute ischemic stroke or high-risk transient ischemic attack. Clinical trials have evaluated the efficacy and safety of ticagrelor on ischemic and bleeding outcomes for different indications and with varying treatment approaches. As a result, there is a large body of clinical evidence demonstrating different degrees of net clinical benefit compared with other platelet inhibitor drugs based on indication, patient characteristics, clinical presentation, treatment duration, and other factors. We provide a review of the major trials of ticagrelor in the context of other randomized trials of clopidogrel and prasugrel to organize the volume of available information, elevate corroborating and conflicting data, and identify potential gaps as areas for further exploration of optimal antiplatelet treatment.

The use of cangrelor in a complex vascular patient: A case report

Medical decision-making surrounding high risk surgical procedures requires extensive consideration about the potential risks and benefits to the patient, including implications for concomitant medications and therapies. Managing cardiovascular risk in patients undergoing non-cardiac surgery is essential for safe and effective patient care. In instances where cardiac revascularization is needed prior to surgery, antiplatelet medication is also needed which can complicate future surgical procedures. This case report describes a patient who underwent percutaneous coronary intervention with drug eluting stent placement, who also needed urgent treatment for expanding thoracic abdominal aortic aneurysm (TAAA). Standard practice for endovascular repair of a TAAA includes placement of a lumbar drain to decrease the risk of spinal cord ischemia, however dual antiplatelet therapy is contraindicated. Cangrelor is the only intravenous platelet P2Y12 receptor inhibitor currently available. The use of Cangrelor, a short-acting P2Y12 inhibitor, was successfully utilized as a bridge in the setting of a patient requiring dual antiplatelet therapy (DAPT) and further surgical intervention. This medication may improve outcomes for this subset of patients.

Ácido acetilsalicílico versus inibidores dos receptores P2Y12 para prevenção secundária em pacientes tratados por meio de intervenção coronária percutânea

Currently, percutaneous coronary intervention with a drug-eluting stent implantation is the main method of myocardial revascularization in tertiary care hospitals, regardless of the clinical presentation of coronary artery disease. It is well known that to be effective, it requires the use of a dual antiplatelet therapy, which is a combination of acetylsalicylic acid and a P2Y12 platelet receptor inhibitor, which plays a key role in preventing thromboses after endoprosthesis implantation and is also indicated to prevent atherothrombotic events in the late clinical course, regardless of the stent model used. After a variable period of time, depending on some factors, such as the clinical presentation of coronary artery disease and the type of stent implanted, this therapy is discontinued, and the main current guidelines recommend interrupting the P2Y12 receptor inhibitor and maintaining acetylsalicylic acid in the long term, as one of the main pharmacological measures for secondary prevention of atherosclerosis. However, recently, due to their greater antiplatelet potency and probable lower potential for significant bleeding, especially in the digestive tract, P2Y12 inhibitors have been considered a valid and attractive option as an antiplatelet agent for long-term use; but this alternative has not been endorsed by guidelines yet. This review discusses the details related to this important decision that must be made by cardiologists when discontinuing the different antithrombotic therapies initially used after percutaneous coronary intervention. In principle, the scarcity of conclusive and normative clinical studies, especially in the population treated by percutaneous intervention, means that acetylsalicylic acid is the only antiplatelet agent with class I indication for secondary prevention of atherosclerosis.

ARCANGELO: an observational, prospective study with acute coronary syndrome patients undergoing percutaneous coronary intervention who receive cangrelor transitioning to oral P2Y12 inhibitors

Abstract Background The use of oral platelet P2Y12 receptor inhibitors, to reduce the risk of thrombotic complications related to Percutaneous Coronary Intervention (PCI), have some limitations in the acute phase, e.g., the delayed onset of action and lack of bioavailability in critical patients. Cangrelor is the only intravenous P2Y12 inhibitor, which based on its quick onset and offset of action is a valid alternative option for antiplatelet therapy, particularly for patients who are unable to take oral medications or for whom oral administration is not adequate. Notably, during the clinical development program of cangrelor, ticagrelor and prasugrel were not marketed and, therefore, the pivotal studies were conducted only with transitioning to clopidogrel. The aim of ARCANGELO study was the evaluation of the safety and effectiveness of cangrelor when administered to patients with Acute Coronary Syndrome (ACS) undergoing PCI in a real-world setting, including patients who received cangrelor transitioning to either clopidogrel, prasugrel, or ticagrelor. Methods Adult patients eligible to PCI for ACS who received cangrelor and who consented to take part in the study in 28 Italian centers, were followed in the 30 days after PCI. Bleedings, major adverse cardiac events (MACEs), and adverse events were recorded. The primary outcome was the incidence of any bleedings, according to BARC (Bleeding Academic Research Consortium) criteria, at 30 days post-PCI. Results A total of 1,004 patients were enrolled and 995 (99.2%) patients were eligible for analysis. Median (IQR) age was 65 (56-73) years, and 771 (77.5%) patients were males. 597 (59.9%) patients had ST-segment Elevation Myocardial Infarction; 509 (51.2%) patients had multi-vessel vessel coronary artery disease. A radial artery access was used in 926 (93.1%) patients and drug-eluting stents were implanted in almost all patients (n=972, 97.7%). All 995 patients included in the analysis received 30 micrograms/kg by intravenous bolus and 4 micrograms/kg/min by intravenous infusion. 730 patients (73.4%) were then transitioned to ticagrelor, 127 (12.8%) to prasugrel, and 138 (13.9%) to clopidogrel. 52 (5.2%) (95% CI 3.9% - 6.8%) patients experienced at least one bleeding event up to 30 days post-PCI. Five patients (0.5%) experienced at least one BARC type 3-5 (moderate-severe) bleeding (all type 3). Fourteen (1.4%) patients presented with at least one MACEs during observation (6 [0.6%] death, 7 [0.7%] myocardial infarction, 2 [0.2%] stent thrombosis). Six (0.6%) patients experienced at least one Treatment-Emergent Adverse Events related to cangrelor. Conclusions The results of this large real-world evidence study confirm that the use of cangrelor in patients with ACS undergoing PCI and transition strategy to the currently used P2Y12 oral inhibitors is safe and effective in daily practice.

Optimising antithrombotic therapy after ACS and PCI

Dual antiplatelet therapy, combining aspirin with a platelet P2Y12 receptor inhibitor, is the standard treatment for acute coronary syndrome patients undergoing percutaneous coronary intervention. The optimal type and duration of dual antiplatelet therapy depend on the patient's risk for ischemic and hemorrhagic complications. De-escalation strategies, such as switching to a less potent P2Y12 inhibitor, reducing the dose, or discontinuing one of the antiplatelet agents, may be suitable for high-risk bleeding patients with low risk of recurrent ischemic events, and platelet function testing and genetic testing can guide de-escalation. For patients at high ischemic risk, strategies include drug switching, dose escalation, or adding a new drug. Patients at high ischemic and hemorrhagic risk require individualized treatment decisions and trade-off considerations.

Features of antiplatelet therapy with P2Y12 receptor inhibitors in patients with myocardial infarction according to the Russian Register of Acute Myocardial Infarction REGION-MI.

Aim To study specific features of administering platelet P2Y12 receptor inhibitors to patients with myocardial infarction (MI) in real-life clinical practice; to reveal a possible inconsistency of the therapy with clinical guidelines; to evaluate the patients' compliance with the medication at the outpatient stage; and to outline major direction for improving quality of the antiplatelet treatment.Material and methods REGION-MI is a multicenter prospective, observational study. The observational period is divided into 3 stages: during the stay in the hospital and at 3 and 12 months following the inclusion into the registry. Information about the drug therapy (used at the time of hospitalization, administered before the hospitalization, received in the hospital, and prescribed at discharge from the hospital) was recorded in the patient's individual registration card. Information about the antiplatelet treatment at 6 months following enrollment into the study was obtain by phone.Results The study included 4 553 patients. Dual antiplatelet therapy was administered after MI to 94.4 % patients: clopidogrel was administered to 52 %, ticagrelor to 42.2 %, and prasugrel to 11 patients (0.2 %). Ticagrelor was administered significantly more frequently in ST segment elevation myocardial infarction (STEMI) than in NSTEMI, 45 % and 33 %, respectively (p<0.001); clopidogrel was also administered more frequently to patients with STEMI than with NSTEMI, 59 % and 50 %, respectively. According to ARC-HBR criteria, in MI and a high risk of bleeding, clopidogrel was administered more frequently than ticagrelor (p <0.001). Ticagrelor was significantly more frequently administered to patients with MI and a low risk of bleeding than to patients with a high risk (p<0.001). In STEMI and a low risk of bleeding, ticagrelor was administered somewhat more frequently than clopidogrel, 56 % and 44 %, respectively (р<0.05). In NSTEMI and a low risk of bleeding, clopidogrel was administered more frequently than ticagrelor, 53 % and 47 %, respectively (p<0.05). At 6 months post-MI, 94 % of patients continued taking one of the P2Y12 inhibitors.Conclusion According to data of the REGION-MI registry, the frequency of administering P2Y12 inhibitors to patients with acute MI was high, and the patients' compliance with this therapy was high at 6 months following MI. Although ticagrelor (the most available drug of all powerful platelet P2Y12 receptor inhibitors) has been prescribed more frequently in the recent years, a definite reserve exists for increasing the frequency of its administration. This is particularly important with a low risk of bleeding and the absence of requirement for anticoagulants. Thus, the prognosis for MI patients can be considerably improved.

Shortenеd and prolonged dual antiplatelet therapy after percutaneous coronary interventions – why, when and how?

The antithrombotic therapy is an important part of medical treatment in percutaneous coronary interventions (PCI). The so called dual antiplatelet therapy (DAPT), usually including acetyl salicylic acid (aspirin) plus platelet P2Y12 receptor inhibitors is an important part of that therapy. The careful balance between the protective effect regarding thrombotic/ischemic events and the risk of bleeding is an important task of the attending physician. Apart of the standard dosing regiments, in some of the cases a judgment regarding shortened or prolonged DAPT, as its de-escalation is mandatory. To present the causes and the way of application of that individualized approach in patients with PCI is the aim of this review. 

P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention.

For 20 years, dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and a platelet P2Y12 receptor inhibitor, has been the gold standard of antithrombotic pharmacology after percutaneous coronary intervention (PCI). In the past 5 years, several investigations have challenged this paradigm by testing the efficacy and safety of P2Y12 inhibitor monotherapy (that is, without aspirin) following a short course of DAPT. Collectively, these studies suggested a reduction in the risk of major bleeding and no significant increase in thrombotic or ischaemic events compared with guideline-recommended DAPT. Current recommendations are evolving to inform clinical practice on the ideal candidates for P2Y12 inhibitor monotherapy after PCI. Generalizing the results of studies of P2Y12 inhibitor monotherapy requires a thorough understanding of their design, populations, interventions, comparators and results. In this Review, we provide an up-to-date overview on the use of P2Y12 inhibitor monotherapy after PCI, including supporting pharmacodynamic and clinical evidence, practical recommendations and future directions.

The role of platelet glycoprotein IIb / IIIa inhibitors in current treatment of acute coronary syndrome.

Current management of patients with acute coronary syndrome (ACS) includes a dual antiplatelet therapy with acetylsalicylic acid and a platelet P2Y12 receptor inhibitor. For patients without a high risk of bleeding, prasugrel and ticagrelor are preferred, since their effect is more pronounced, less dependent on metabolism of a specific patient, and occurs faster that the effect of clopidogrel. The prescription rate of platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor inhibitors has considerably decreased. However, these drugs remain relevant in percutaneous coronary interventions in patients with a high risk of coronary thrombosis or a massive coronary thrombus, in thrombotic complications of the procedure, and in the "no-reflow" phenomenon. The intravenous route of GP IIb / IIIa inhibitor administration provides their effectiveness in patients with difficulties of drug intake or with impaired absorption of oral medications. This review presents clinical and pharmacological characteristics of various GP IIb / IIIa inhibitors and data of randomized clinical studies and registries of recent years that evaluated results of their use in patients with ACS.

Construction of novel antiplatelet modified polyethersulfone membrane and study into its blood compatibility

Blood purification therapy is widely used in patients with renal insufficiency and severe infections, where membrane-associated thrombosis is a side effect. How to improve the hemocompatibility of dialysis membranes and reduce thrombosis is a focus of current research, in which platelets play a key role. However, few dialysis membranes that directly inhibit platelets have been developed to date. In this study, a polyethersulfone (PES) membrane was modified with ticagrelor, a platelet P2Y12 receptor inhibitor, and detailed characterization was performed. The ticagrelor modified PES membrane (TMPES) showed good hydrophilicity and anti-protein adsorption and significantly inhibited platelet adhesion, aggregation, and activation, which demonstrated good antithrombotic properties. In addition, the membrane had excellent red blood cell (RBC) compatibility, anticoagulant, and antiinflammatory effects, which demonstrated superior biosafety in cell and animal experiments. Therefore, the TMPES dialysis membrane could have potential in clinical applications.

Persistent risk of vascular complications and efficacy of prolonged dual antiplatelet therapy after myocardial infarction

The article discusses data on the duration of risk retention and the main cause of vascular complications in patients with acute coronary syndrome. Preconditions for prolonged use of dual antiplatelet therapy after myocardial infarction are presented. The authors consider the results of a large, prospective, randomized, placebo-controlled, multinational PEGASUS-TIMI 54 study evaluating the efficacy and safety of the long-term use of acetylsalicylic acid combined with ticagrelor (P2Y12 platelet receptor blocker) in patients with a high risk of thrombotic complications of atherosclerosis in the period from 1 to 3 years after myocardial infarction. The article presents an analysis of optimal approaches to prolonged double antiplatelet therapy after myocardial infarction, taking into account the results of the PEGASUS-TIMI 54 study, which laid the foundation for current clinical guidelines. The PEGASUS-TIMI 54 study demonstrated the benefits of prolonged dual antiplatelet therapy for at least 4 years after myocardial infarction in patients with a high risk of atherothrombotic complications and confirmed the expediency to reduce the dose of ticagrelor from 90 to 60 mg twice daily for 1 year after the onset of the disease to ensure the best balance of efficacy and safety of treatment. The possibility of prolonging double antiplatelet therapy using a combination of ASA and ticagrelor at a dose of 60 mg twice daily for 1 year after myocardial infarction is provided for in the guidelines for medical use of ticagrelor and is enshrined in existing clinical guidelines. Presently, ticagrelor is the only P2Y12 platelet receptor inhibitor approved in the Russian Federation as an adjunct to ASA for the long-term prevention of atherothrombotic cardiovascular events.

Monoterapia com inibidores dos receptores P2Y12 em pacientes tratados por meio de intervenção coronária percutânea

Since the mid-1990s, the dual antiplatelet therapy, consisting of the association between acetylsalicylic acid and a platelet P2Y12 receptor inhibitor, is the core of thrombosis prevention after coronary stent implantation, regardless of the models used. It is also used to prevent the occurrence of atherothrombotic events in the late phase after the intervention. The clinical presentation of coronary artery disease influences the duration of dual therapy, which tends to be longer in treated cases of acute coronary syndrome (usually for one year), when compared to cases of chronic coronary disease (often for up to 6 months). After this period, the P2Y12 inhibitor is usually discontinued, and monotherapy with aspirin is maintained. However, in the last two decades, it has been observed that prolonged use of two associated antiplatelet agents predisposes treated cases to bleeding complications, with potentially severe consequences – including increased mortality. Thus, alternatives that minimize this risk have been considered and evaluated, such as early discontinuation of acetylsalicylic acid (between 1 and 3 months after discharge), or the so-called monotherapy with P2Y12 inhibitors, aiming to reduce bleeding without compromising prevention of ischemic events. In the last decade, a series of randomized clinical trials evaluated this hypothesis, generally resulting in reduced bleeding complications, although not necessarily of those classified as major, with no significant increase in the most relevant cardiovascular events. This review discusses the main results of these clinical trials and their potential clinical implications for routine cardiology practice.

Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives.

Cangrelor is the only currently available intravenous platelet P2Y12 receptor inhibitor. It is characterized by potent, predictable, and rapidly reversible antiplatelet effects. Cangrelor has been tested in the large CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) program, where it was compared with different clopidogrel regimens, and it is currently indicated for use in patients with coronary artery disease undergoing percutaneous coronary intervention. However, the uptake of cangrelor use varies across the globe and may also include patients with profiles different from those enrolled in the registration trials. These observations underscore the need to fully examine the safety and efficacy of cangrelor in postregistration studies. There are several ongoing and planned studies evaluating the use of cangrelor in real‐world practice which will provide important insights to this extent. The current article provides a review on the pharmacology, clinical studies, contemporary use of cangrelor in real‐world practice, a description of ongoing studies, and futuristic insights on potential strategies on how to improve outcomes of patients undergoing percutaneous coronary intervention.

Ticagrelor use and practice patterns among Canadian cardiac surgeons.

The P2Y12 platelet receptor inhibitor ticagrelor is widely used in patients following acute coronary syndromes or in those who have received coronary stents. Bentracimab is a monoclonal antibody-based reversal agent that is being formally evaluated in a Phase 3 clinical trial. Here, we probe the knowledge, attitudes, and practice patterns of cardiac surgeons regarding their perioperative management of ticagrelor and potential application of a ticagrelor reversal agent. A questionnaire was developed by a working group of cardiac surgeons to inquire into participants' practices and beliefs regarding ticagrelor and disseminated to practicing, Canadian-trained cardiac surgeons. A total of 70 Canadian-trained cardiac surgeons participated. Bleeding risk was identified as the most significant consideration when surgically revascularizing ticagrelor-treated patients (90%). There is variability in the duration of withholding ticagrelor before coronary artery bypass graft procedure in a stable patient; 44.3% wait 3 days and 32.9% wait 4 days or longer. Currently, 15.7% of cardiac surgeons prophylactically give platelet transfusions and fresh frozen plasma intraoperatively following protamine infusion in patients who have recently received ticagrelor. Interestingly, 47.1% of surveyed surgeons were aware of a reversal agent for ticagrelor, 91.4% of cardiac surgeons would consider utilizing a ticagrelor reversal agent if available, and 51.4% acknowledged that the introduction of such an agent would be a major advance in clinical practice. The present survey identified ticagrelor-related bleeding as a major concern for cardiac surgeons. Surgeons recognized the significant unmet need that a ticagrelor reversal agent would address.

Impact of periprocedural morphine use on mortality in STEMI patients treated with primary PCI.

Intravenous morphine (MO) decreases the effect of all oral platelet P2Y12 receptor inhibitors in vitro and observational reports suggest that its use may be associated with larger infarct size. Yet, there are limited data available about the impact of this interaction on clinical outcomes. We studied the effect of MO on mortality in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI using a prospective registry. Of the 1255 patients who underwent primary PCI, 397 received MO based on physician's judgment. Clopidogrel was used as P2Y12 receptor antagonist in all cases. Median follow-up time was 7.5 years with 457 deaths. To adjust for confounding, two propensity score-based procedures were performed: 1 to 1 matching (PSM, 728 cases), and inverse probability of treatment weighting (IPTW) retaining data from all patients. Primary outcome measure was time to all-cause death, whereas predischarge left ventricular ejection fraction (LVEF) was used as secondary end point. An adequate balance on baseline covariates was achieved by both methods. We found no difference in survival as the HR (MO/no MO) was 0.98 (95% confidence interval [CI]: 0.76-1.26), p = 0.86 using PSM and 1.01 (95% CI: 0.84-1.23), p = 0.88 with IPTW. Likewise, distributions of LVEFs were similar using either methods: with PSM, median LVEFs were 50.0% (interquartile range [IQR]: 43.0%-55.3%) vs 50.0% (IQR: 42.0%-55.0%) in the no MO and MO groups, respectively (p = 0.76), whereas using IPTW, they were 50.0% (IQR: 42.5%-55.0%) vs 50.0% (IQR: 41.0%-55.0%), respectively (p = 0.86). Our data suggest that morphine use may have no impact on long-term mortality and on predischarge ejection fraction in STEMI patients treated with primary PCI.

Ticagrelor Plus Aspirin for Stroke or TIA of Atherosclerotic Origin

Ticagrelor is a reversible platelet P2Y12 receptor inhibitor. The recently completed THALES trial, comparing aspirin plus ticagrelor (A+T) versus

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy

BackgroundTo mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.MethodsThis prospective (April 2013–December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.DiscussionThe risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.Trial registrationTrial registration name is “Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy” (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Short- and Midterm Adherence to Platelet P2Y12 Receptor Inhibitors After Percutaneous Coronary Intervention With Drug-Eluting Stents.

In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence. In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence. A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days. We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.

Pharmacological strategy pre- and post-percutaneous coronary intervention in patients with acute coronary syndrome on oral anticoagulation therapy

In patients with atrial fibrillation (AF) who undergo an acute coronary syndrome (ACS), with or without percutaneous coronary intervention and coronary stent implantation, the association of dual antiplatelet therapy with an oral anticoagulant (also known as triple antithrombotic therapy, TAT) increases the risk for major and fatal bleeding. Recently, several trials have evaluated alternative therapeutic regimens to TAT, such as dual antithrombotic therapy (DAT) comprising a direct oral anticoagulant and a platelet P2Y12 receptor inhibitor. In the context of patients treated with percutaneous coronary intervention, these regimens have generally been associated with a reduction in bleeding that was not accompanied by a substantial increase in ischemic events. However, the net benefit of DAT is more controversial in the case of patients at higher thrombotic risk, such as patients with ACS. This review, based on the available literature, describes the best peri-procedural and post-procedural antithrombotic strategies for patients with AF and ACS.

Aggregometry Response to Half-dose Prasugrel inFlow-diverting Stent Implantation.

The aim of this study was to determine whether half-dose loading (30 mg) of prasugrel is sufficient to achieve adequate platelet inhibition, and whether such aloading dose of prasugrel together with aspirin followed by a10 mg/day prasugrel maintenance, could serve as afirst-line antiplatelet strategy for patients undergoing flow-diverting stent (FDS) implantation. Data from agroup of consecutive patients treated for intracranial aneurysm with FDS were retrospectively collected. Platelet P2Y12 receptor responsiveness was assessed by arapid platelet function test just prior to the procedure. All ischemic and hemorrhagic complications as well as morbidity and mortality rates were documented. Atotal of 138 patients with 153 aneurysms (32were symptomatic and 121 were incidental) underwent FDS treatment in atotal of 147 loading sessions. Adequate platelet inhibition was obtained in 136/138 (98.5%) patients and 145/147 (98.6%) loading sessions. Overall, there was one case of (hemorrhagic) mortality (0.7%), one of (ischemic) morbidity (0.7%), one of symptomatic (hemorrhagic) clinical complications without permanent deficits (0.7%), and six transient ischemic attacks (4.1%). The 6‑month control angiography, available for all patients, revealed a95.4% aneurysm occlusion rate. Half-dose (30 mg) prasugrel loading results in effective platelet P2Y12 receptor inhibition in more than 98% of patients. Dual antiaggregant loading with half dose prasugrel followed by prasugrel maintenance as afirst-line therapy appears to be feasible in patients treated with FDS implantation for intracranial aneurysm.