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Expert Review of Clinical Pharmacology Oct 2022Platelets play a key role in arterial thrombosis and antiplatelet therapy is pivotal in the treatment of cardiovascular disease. Current antiplatelet drugs target... (Review)
Review
INTRODUCTION
Platelets play a key role in arterial thrombosis and antiplatelet therapy is pivotal in the treatment of cardiovascular disease. Current antiplatelet drugs target different pathways of platelet activation and show specific pharmacodynamic and pharmacokinetic characteristics, implicating clinically relevant drug-drug interactions.
AREAS COVERED
This article reviews the role of platelets in hemostasis and cardiovascular thrombosis, and discusses the key pharmacodynamics, drug-drug interactions and reversal strategies of clinically used antiplatelet drugs.
EXPERT OPINION
Antiplatelet therapies target distinct pathways of platelet activation: thromboxane A synthesis, adenosine diphosphate-mediated signaling, integrin αβ (GPIIb/IIIa), thrombin-mediated platelet activation via the PAR1 receptor and phosphodiesterases. Key clinical drug-drug interactions of antiplatelet agents involve acetylsalicylic acid - ibuprofen, clopidogrel - omeprazole, and morphine - oral P2Y inhibitors, all of which lead to an attenuated antiplatelet effect. Platelet function and genetic testing and the use of scores (ARC-HBR, PRECISE-DAPT, ESC ischemic risk definition) may contribute to a more tailored antiplatelet therapy. High on-treatment platelet reactivity presents a key problem in the acute management of ST-elevation myocardial infarction (STEMI). A treatment strategy involving early initiation of an intravenous antiplatelet agent may be able to bridge the gap of insufficient platelet inhibition in high ischemic risk patients with STEMI.
Topics: Humans; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Drug Therapy, Combination; Clopidogrel; Thrombosis; Purinergic P2Y Receptor Antagonists
PubMed: 36065676
DOI: 10.1080/17512433.2022.2121702 -
Journal of Neurointerventional Surgery Feb 2016Antiplatelet agents are essential for the successful management of patients undergoing a variety of neurointerventional procedures. The most commonly used anti-platelet... (Review)
Review
Antiplatelet agents are essential for the successful management of patients undergoing a variety of neurointerventional procedures. The most commonly used anti-platelet agents are aspirin, clopidogrel and prasugrel. However, there exist an alternative class of anti-platelet agent that may prove useful for neurointerventionists. In particular a drug called cilostazol may have numerous added advantages above and beyond its antiplatelet effect that may be valuable for our patients. In this short review we aim to highlight some of these potential advantages.
Topics: Cilostazol; Humans; Neurosurgical Procedures; Platelet Aggregation Inhibitors; Postoperative Complications; Stents; Tetrazoles
PubMed: 25526917
DOI: 10.1136/neurintsurg-2014-011570 -
British Journal of Haematology Jun 2017The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an... (Review)
Review
The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Aspirin; Cardiovascular Diseases; Drug Discovery; Forecasting; Hematologic Diseases; Hemorrhage; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Plant Bark; Platelet Aggregation Inhibitors; Salix
PubMed: 28106908
DOI: 10.1111/bjh.14520 -
Stroke Nov 2022It has previously been shown in several animal experiments that platelet GPVI (glycoprotein VI) contributes to thrombosis, particularly in ischemic stroke. Moreover,... (Review)
Review
It has previously been shown in several animal experiments that platelet GPVI (glycoprotein VI) contributes to thrombosis, particularly in ischemic stroke. Moreover, GPVI levels are upregulated in stroke patients. This review describes the therapeutic roles of anti-GPVI antibody in preclinical models of ischemic stroke and provides the current evidence for potential benefits of glenzocimab, a Fab fragment of humanized anti-GPVI monoclonal antibody, in stroke patients. Anti-GPVI antibody, JAQ1, significantly decreased infarct volume and improved neurological function in mice with transient middle cerebral artery occlusion, a model of ischemic stroke, with no or minor bleeding tendency. Intravenous injection of glenzocimab in nonhuman primates produced rapid inhibition of ex vivo platelet aggregation induced by collagen (a GPVI ligand). Complete platelet inhibition is observed at 30 minutes following administration without increasing the risk of bleeding. In humans, glenzocimab is well tolerated and produces dose-dependent antiplatelet activity. More importantly, glenzocimab (125-1000 mg) was safe when administered as soon as possible (<3 hours) following reperfusion with the r-tPA (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke. Although glenzocimab 1000 mg (a selected dose) did not demonstrate a significant improvement in overall clinical outcomes, it appeared to provide benefits in severe cases and in patients who required thrombectomy. This promising efficacy together with a good safety profile of glenzocimab warrant further investigation in phase III (ACTISAVE [Adaptive Efficacy and Safety Study of Glenzocimab Used as an Add-On Therapy on Top of Standard of Care in the 4.5 Hours Following an Acute Ischemic Stroke]) clinical study.
Topics: Humans; Animals; Mice; Platelet Aggregation Inhibitors; Tissue Plasminogen Activator; Platelet Membrane Glycoproteins; Ischemic Stroke; Ligands; Antibodies, Monoclonal, Humanized; Immunoglobulin Fab Fragments; Stroke; Collagen
PubMed: 36128904
DOI: 10.1161/STROKEAHA.122.039790 -
Journal of the American College of... Jul 2023
Topics: Humans; Platelet Aggregation Inhibitors; Coronary Artery Disease; Secondary Prevention; Aspirin; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Drug Therapy, Combination; Treatment Outcome; Percutaneous Coronary Intervention
PubMed: 37407109
DOI: 10.1016/j.jacc.2023.05.022 -
International Journal of Stroke :... Apr 2015There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator... (Meta-Analysis)
Meta-Analysis Review
Prior antiplatelet agent use and outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: a meta-analysis of cohort studies and randomized controlled trials.
BACKGROUND
There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke.
AIM
We performed a systematic review with a final meta-analysis to evaluate the efficacy and safety of prior antiplatelet use before intravenous recombinant tissue plasminogen activator for acute ischemic stroke.
SUMMARY OF REVIEW
We searched PubMed and Embase databases from 1997 to 2014. Primary outcome was functional outcome at the end of follow-up; secondary outcomes were symptomatic intracranial hemorrhage and recanalization rate. The meta-analysis was performed with Review Manager 5.2 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). Eleven studies with a total of 19,453 patients were included. A total of 6517 (33.5%) patients who had received intravenous recombinant tissue plasminogen activator were taking antiplatelet agent before stroke onset. Pooled analysis demonstrated a clear trend that previous antiplatelet users had a reduced probability of good outcome, although it was not conventionally statistically significant (OR 0.86; 95% CI 0.73-1.01; P = 0.06). There was no difference in recanalization rate between two groups (OR 1.23; 95% CI 0.30-4.99; P = 0.77). The risk of symptomatic intracranial hemorrhage was significantly increased in the antiplatelet group (OR 1.65; 95% CI 1.44-1.90; P < 0.01).
CONCLUSIONS
In acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator therapy, prior antiplatelet agent use did not lead to a significant difference in functional outcome, although it significantly increased the risk of symptomatic intracranial hemorrhage. Recanalization rate was not different between two groups. In the subgroup analysis, prior clopidogrel mono therapy may not increase the risk of symptomatic intracranial hemorrhage, which will need further studies to confirm.
Topics: Cohort Studies; Databases, Bibliographic; Humans; Injections, Intravenous; Ischemia; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 25545076
DOI: 10.1111/ijs.12431 -
American Journal of Health-system... Jun 2008The pharmacology, pharmacokinetics, safety, and adverse effects of prasugrel, a novel antiplatelet agent, are described. (Review)
Review
PURPOSE
The pharmacology, pharmacokinetics, safety, and adverse effects of prasugrel, a novel antiplatelet agent, are described.
SUMMARY
Prasugrel is a third-generation thienopyridine. Like clopidogrel, prasugrel is a prodrug requiring hepatic metabolism to its active form to bind irreversibly to the P2Y(12) adenosine diphosphate receptor and inhibits platelet aggregation for the life of the platelet. Prasugrel's pharmacokinetic profile has not been clearly defined. Several preclinical and early-phase clinical trials of prasugrel have been completed. Five trials have assessed the platelet aggregation of prasugrel alone or compared with placebo or clopidogrel. Certain populations with acute coronary syndrome (ACS) may be at higher risk for major bleeding episodes leading to fatal events when using prasugrel with other antithrombotic agents and antiplatelet agents. Information on drug or food interactions with prasugrel is limited. Since prasugrel is still under investigation, an official recommended dosage regimen has yet to be determined. Clinical trials are still being conducted to determine prasugrel's exact place in therapy. In early trials, prasugrel has demonstrated a faster onset of action, higher rate of platelet inhibition, and lower rate of response variability compared with clopidogrel.
CONCLUSION
Prasugrel has demonstrated a greater platelet inhibition and a decreased incidence of ischemic events compared with clopidogrel, but with an increased incidence of bleeding events. Future studies with prasugrel should determine its optimal dosage regimen to minimize bleeding risks and evaluate its outcomes in ACS and safety profile in special patient populations.
Topics: Acute Coronary Syndrome; Animals; Clopidogrel; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Thiophenes; Thrombolytic Therapy; Ticlopidine
PubMed: 18499874
DOI: 10.2146/ajhp070496 -
CNS Drugs Dec 2010Oral antiplatelet drugs, including aspirin, clopidogrel and extended-release dipyridamole, are widely prescribed for the secondary prevention of vascular events,... (Review)
Review
Oral antiplatelet drugs, including aspirin, clopidogrel and extended-release dipyridamole, are widely prescribed for the secondary prevention of vascular events, including stroke. Despite the benefits of antiplatelet therapy, 10−20% of patients experience a recurrent vascular event while taking antiplatelet medication. This article discusses the concept of antiplatelet resistance in general, focusing on aspirin resistance in particular, as a poorly defined cause of recurrent vascular events. Factors such as the lack of a standardized method to diagnose aspirin resistance and a poor clinical correlation with laboratory assays make the treatment of aspirin nonresponders difficult. In addition, there are confounding conditions such as diabetes mellitus that can affect aspirin resistance and determine a different course of treatment for these patients. Other antiplatelet options may also have resistant subpopulations; thus, alternative strategies for the secondary stroke patient must be explored.
Topics: Aspirin; Clopidogrel; Dipyridamole; Drug Resistance; Humans; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticlopidine
PubMed: 20932071
DOI: 10.2165/11539160-0000000000-00000 -
Cardiology in Review 2011The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet... (Review)
Review
The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet medications that are used in addition to aspirin include the thienopyridines, clopidogrel and prasugrel, but there are several limitations to the use of these medications. Clopidogrel and prasugrel irreversibly bind to the P2Y12 receptor, creating a prolonged antiplatelet effect which can be undesirable when surgery is needed. Clopidogrel requires hepatic activation and produces variable platelet inhibition based on genetic polymorphisms. Prasugrel has more consistent platelet inhibition than clopidogrel but carries with it an increased risk of serious bleeds. Ticagrelor is a drug in a new chemical class that reversibly binds the P2Y12 receptor and noncompetitively blocks adenosine diphosphate-induced platelet activation. It was specifically designed to address the limitations of the available antiplatelet agents while maintaining comparable or better antiplatelet effects. It does not require metabolic activation and demonstrates greater platelet inhibition, a faster offset of action and comparable bleeding risk compared to clopidogrel. The pivotal PLATO (The Study of Platelet Inhibition and Patient Outcomes) trial in patients with an acute coronary syndrome demonstrated improved cardiovascular outcomes, including a reduction in myocardial infarctions and vascular events using ticagrelor as compared to clopidogrel with comparable rates of major bleeds. A puzzling finding from that trial was the lack of benefit with ticagrelor in patients enrolled from the United States, which has led to ticagrelor not being approved at this time in this country. The main adverse events with ticagrelor are bleeding and dyspnea, the latter of which is of unclear etiology and of unknown long-term clinical concern. In summary, ticagrelor is an exciting new oral antiplatelet drug that seems to be more efficacious than clopidogrel, with comparable safety. Whether issues of geographic disparities in response and the unusual side effect of dyspnea ultimately prove problematic has yet to be determined. Nonetheless, ticagrelor is a drug that has the potential to change the standard of care of patients with acute coronary syndromes.
Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Clopidogrel; Drug Resistance; Dyspnea; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Ticagrelor; Ticlopidine
PubMed: 21285670
DOI: 10.1097/CRD.0b013e3182099d86 -
The Korean Journal of Gastroenterology... Nov 2020The Korean guidelines for the Clinical Guidelines for Drug-related Peptic Ulcer were revised under the Korean College of Helicobacter and Upper Gastrointestinal Research... (Review)
Review
The Korean guidelines for the Clinical Guidelines for Drug-related Peptic Ulcer were revised under the Korean College of Helicobacter and Upper Gastrointestinal Research in 2020. In these revised guidelines, treatment for infections is recommended in patients with a history of peptic ulcers and are receiving long-term low-dose aspirin therapy to prevent peptic ulcers and complications. The maintenance of anti-ulcer drugs, such as proton pump inhibitors, is also recommended after eradication if patients require other antiplatelet agents or anticoagulants. Regardless of eradication, when patients with a history of peptic ulcer take long-term low dose aspirin, the concomitant use of a proton pump inhibitor according to the severity of the peptic ulcer is recommended.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Aspirin; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Platelet Aggregation Inhibitors; Proton Pump Inhibitors
PubMed: 33234770
DOI: 10.4166/kjg.2020.140