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Blood Reviews Jan 2020Antiplatelet medications have long been the mainstay for secondary prevention in cardiovascular disorders. More recently, with the advent of coronary stents, there has... (Review)
Review
Antiplatelet medications have long been the mainstay for secondary prevention in cardiovascular disorders. More recently, with the advent of coronary stents, there has been an increased use of more potent antiplatelet agents to prevent stent occlusion. Since these drugs are antithrombotic, it is not unusual for them to be associated with serious bleeding, particularly intracranial and gastrointestinal haemorrhage. There are no robust guidelines on how to manage these clinical situations, although there have been some important studies published recently in this area. Similarly, there is very limited evidence on how to manage urgent surgery in patients receiving these medications. In this review, we provide updated guidance on the management of bleeding and surgery on antiplatelet drugs while stressing the need for further studies to provide evidence-based guidelines.
Topics: Hemorrhage; Humans; Platelet Aggregation Inhibitors
PubMed: 31648803
DOI: 10.1016/j.blre.2019.100619 -
European Heart Journal Jul 2023
Topics: Humans; Aspirin; Platelet Aggregation Inhibitors; Perioperative Care
PubMed: 37155334
DOI: 10.1093/eurheartj/ehad246 -
Pharmacology 2023Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in...
BACKGROUND
Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in combination with OAC is recommended after PCI for 6-12 months. Clopidogrel is used most frequently in this setting. However, data comparing P2Y12 inhibition with clopidogrel versus cyclooxygenase inhibition by acetylsalicylic acid (ASA, aspirin) is missing. It is well known that the antiplatelet effects of ASA and clopidogrel are frequently impaired (high on-treatment platelet reactivity [HTPR]). In this pilot investigation, we compared the antiplatelet effects of clopidogrel versus ASA.
METHODS
In this retrospective single-center database analysis, we investigated platelet reactivity by light transmission aggregometry in patients under different antiplatelet regimes. Results were presented as maximum of aggregation (MoA). HTPR to ASA and to clopidogrel were assessed.
RESULTS
755 patients were enrolled. 677 were on ASA, 521 were on clopidogrel, and 198 had OAC. Overall mean age was 73 ± 13.4 years, and 458 (60.7%) were male. HTPR to ASA occurred in 94/677 patients (13.9%), and mean arachidonic acid-induced MoA was 14.15 ± 19.04%. HTPR to clopidogrel occurred in 241/521 patients (46.3%), and mean adenosine diphosphate-induced MoA was 50.06 ± 20.42%. HTPR to clopidogrel was significantly more frequent than HTPR to ASA; single antiplatelet therapy (SAPT)-mono ASA: 27/199 (13.6%) versus mono clopidogrel: 6/18 (33.3%); p = 0.037; SAPT with OAC-OAC with ASA: 8/35 (22.9%) versus OAC with clopidogrel: 27/60 (45%); p = 0.046. Same difference in HTPR contingency could be shown in subgroups of dual antiplatelet therapy and ASA + clopidogrel + OAC therapy.
CONCLUSION
Impaired pharmacodynamic response to clopidogrel was more frequent as HTPR to ASA. Hence, ASA should be tested in combination with OAC post-PCI.
Topics: Humans; Male; Middle Aged; Aged; Aged, 80 and over; Female; Clopidogrel; Aspirin; Ticlopidine; Percutaneous Coronary Intervention; Retrospective Studies; Platelet Aggregation Inhibitors; Blood Platelets; Platelet Aggregation
PubMed: 36463859
DOI: 10.1159/000527816 -
Journal of Intensive Care Medicine Jan 2021Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care...
INTRODUCTION
Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage.
METHODS
We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution.
RESULTS
Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], < .001).
CONCLUSIONS
Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage.
Topics: Adult; Health Care Costs; Hospital Mortality; Hospitalization; Humans; Intensive Care Units; Intracranial Hemorrhages; Length of Stay; Platelet Aggregation Inhibitors; Retrospective Studies
PubMed: 31741418
DOI: 10.1177/0885066619885347 -
American Journal of Health-system... Sep 2019Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing... (Review)
Review
PURPOSE
Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and stenting are reviewed.
SUMMARY
Up to 8% of patients undergoing PCI have AF and thus require both antiplatelet and anticoagulation therapies, which put them at increased risk for bleeding. Current literature suggests that using a single antiplatelet agent in combination with oral anticoagulation with a direct-acting oral anticoagulant (i.e., dual therapy) is effective and associated with less bleeding risk than triple therapy (dual antiplatelet therapy plus an oral anticoagulant) in patients with AF undergoing PCI with stent placement. The most recently studied dual therapy regimens consist of clopidogrel in combination with apixaban, rivaroxaban, or dabigatran. Guidelines recommend use of an oral anticoagulant plus clopidogrel and aspirin for a short period of time. In general, aspirin should be discontinued in most patients at discharge. In patients with a high risk of thrombosis, aspirin can be continued for up to 1 month. Dual therapy should be continued for 12 months, with oral anticoagulant monotherapy continued thereafter.
CONCLUSION
A review of current literature on antithrombotic therapy in patients with AF undergoing PCI and subsequent coronary artery stenting indicates that the favored regimen is dual therapy consisting of clopidogrel with rivaroxaban, apixaban, dabigatran, or a vitamin K antagonist. Aspirin may be used in the periprocedural period but should be discontinued thereafter to reduce the risk of bleeding. Decisions regarding specific agents and duration of treatment should be based on thrombotic risk, bleeding risk, and patient preference.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Clinical Decision-Making; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Humans; Patient Preference; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Practice Guidelines as Topic; Risk Assessment; Stents; Thrombosis; Time Factors
PubMed: 31505555
DOI: 10.1093/ajhp/zxz152 -
Platelets Jan 2021Acute coronary syndromes (ACS) are a global cause of mortality and morbidity that affect millions of lives worldwide. Following atherosclerotic plaque rupture, platelet... (Review)
Review
Acute coronary syndromes (ACS) are a global cause of mortality and morbidity that affect millions of lives worldwide. Following atherosclerotic plaque rupture, platelet activation and aggregation are the two major elements that initiate thrombus formation inside a coronary artery, which can obstruct blood flow and cause myocardial ischemia; ergo, antiplatelet therapy forms a major part of the treatment strategy for ACS. Patients with ACS routinely receive dual antiplatelet therapy (DAPT), which consists of aspirin and a platelet P2Y inhibitor to both treat and prevent atherothrombosis. Use of platelet glycoprotein (GP) IIb/IIIa inhibitors is now limited due to the risk of severe bleeding and thrombocytopenia. Thus, administration of GPIIb/IIIa inhibitors is generally restricted to bail out thrombotic events associated with PCI. Furthermore, current antiplatelet medications mainly rely on thromboxane A and P2Y inhibition, which have broad-acting effects on platelets and are known to cause bleeding, which especially limits the long-term use of these agents. In addition, not all ACS patients treated with current antiplatelet treatments are protected from recurrence of arterial thrombosis, since many platelet mechanisms and activation pathways remain uninhibited by current antiplatelet therapy. Pharmacological antagonism of novel targets involved in platelet function could shape future antiplatelet therapies that could ultimately lead to more effective or safer therapeutic approaches. In this article, we focus on inhibitors of promising targets that have not yet been introduced into clinical practice, including inhibitors of GPVI, protease-activated receptor (PAR)-4, GPIb, 5-hydroxytryptamine receptor subtype 2A (5-HT), protein disulfide isomerase, -selectin and phosphoinositide 3-kinase β.
Topics: Acute Coronary Syndrome; Humans; Platelet Aggregation Inhibitors
PubMed: 32529932
DOI: 10.1080/09537104.2020.1763731 -
Bioorganic & Medicinal Chemistry Letters May 2023Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that...
Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity. It was found that GSK3β inhibition by 2-oxindoles correlates with inhibition of platelet activation only for compounds 1b and 5a. Albeit, in vitro antiplatelet activity matched well with in vivo anti-thrombosis activity. The most active GSK3β inhibitor 5a exceeds antiplatelet activity of acetylsalicylic acid in vitro by 10.3 times and antithrombotic activity in vivo by 18.7 times (ED 7.3 mg/kg). These results support the promising role of GSK3β inhibitors for development of novel antithrombotic agents.
Topics: Humans; Platelet Aggregation Inhibitors; Oxindoles; Fibrinolytic Agents; Glycogen Synthase Kinase 3 beta; COVID-19; Thrombosis; Platelet Aggregation
PubMed: 37054760
DOI: 10.1016/j.bmcl.2023.129283 -
Hellenic Journal of Cardiology : HJC =... 2019
Topics: Blood Platelets; Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors
PubMed: 32014559
DOI: 10.1016/j.hjc.2020.01.001 -
Expert Review of Hematology Oct 2020Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the... (Review)
Review
INTRODUCTION
Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety.
AREAS COVERED
Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients.
EXPERT OPINION
While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.
Topics: Anemia, Sickle Cell; Blood Coagulation; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Monitoring; Humans; Molecular Structure; Platelet Activation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Thrombophilia; Ticagrelor; Treatment Outcome
PubMed: 32972255
DOI: 10.1080/17474086.2020.1817736 -
World Journal of Urology Nov 2020The perioperative management of patients who are receiving antithrombotic (antiplatelet or anticoagulant) therapy and require urologic surgery is challenging due to the... (Review)
Review
PURPOSE
The perioperative management of patients who are receiving antithrombotic (antiplatelet or anticoagulant) therapy and require urologic surgery is challenging due to the inherent risk for surgical bleeding and the need to minimize thromboembolic risk. The aim of this review is to assess the quality and consistency of clinical practice guidelines (CPGs) and clinical practice recommendations (CPRs) on this topic, and to summarize the evidence and associated strength of recommendations relating to perioperative antithrombotic management.
METHODS
A pragmatic search of electronic databases and guidelines websites was performed to identify relevant CPGs/CPRs. The AGREE II (Appraisal of Guidelines for REsearch and Evaluation) instrument was used to assess the methodological quality and integrity of the CPGs.
RESULTS
The CPGs provided by the European Association of Urology (EAU), the American College of Chest Physicians (ACCP) and the European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA), and the CPRs provided by the International Consultation on Urological Disease (ICUD)/American Urologic Association (AUA) were retrieved and reviewed. The 3 CPGs were critically assessed using the AGREE II instrument. Inconsistent recommendations were provided based on the indication for antithrombotic medication, the antiplatelet/anticoagulant agent and the type of urological procedure. Based on the AGREE II tool for CPG assessment, the EAU CPGs scored higher (83.3 points) compared to the ESC/ESA (75 points) and ACCP CPG (66.7 points).
CONCLUSION
The perioperative management of antithrombotic therapy in urological patients is potentially challenging but inconsistent CPG of varying quality may create uncertainty as to best practices to minimize thromboembolic and bleeding risk.
Topics: Anticoagulants; Humans; Perioperative Period; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Factors; Urologic Surgical Procedures
PubMed: 31938841
DOI: 10.1007/s00345-020-03078-2