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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 :... Aug 2016Vorapaxar, a novel platelet thrombin protease-activated receptor 1 blocker, is currently approved for post-myocardial infarction and peripheral artery disease... (Review)
Review
BACKGROUND AND PURPOSE
Vorapaxar, a novel platelet thrombin protease-activated receptor 1 blocker, is currently approved for post-myocardial infarction and peripheral artery disease indications on top of clopidogrel or/and aspirin. We sought to summarize the conflicting stroke data after vorapaxar for justifying a secondary stroke prevention trial.
METHODS
Analyses of the stroke data after vorapaxar yielded from thrombin-receptor antagonist vorapaxar in acute coronary syndromes (TRACER) and TRA2P clinical trials, and affiliated Food and Drug Administration (FDA) reviews.
RESULTS
The stroke data are mixed, with catastrophic 2.5 excess of intracranial bleeding risks (HR = 2.52; 95% CI = 1.46-4.36, p < 0.0001); trend to worsened second stroke rates (13.0% vs. 11.7%; HR = 1.03; 95% CI = 0.85-1.25, p = NS), but a hint towards less primary ischemic strokes in vorapaxar indicated population (HR = 0.57; 95% CI = 0.43 to 0.75; p < 0.001). These conflicting data are not solely attributed to vorapaxar, but rather reflect unreasonably aggressive triple antiplatelet strategies utilized frequently in TRA2P and dominant in TRACER. Overall, the FDA-confirmed evidence advocates future vorapaxar secondary stroke prevention trial due to being first-in-class agent, unique pharmakynetics, and exhibiting very mild "comfort zone" antiplatelet profile. The three arm trial testing head-to-head monotherapy with vorapaxar (Zontivity®), versus clopidogrel (Plavix®), and versus extended-released dipyridamole with very low dose aspirin (Aggrenox®) is warranted.
CONCLUSIONS
Vorapaxar may be superior to currently recommended antiplatelet strategies and should be tested as a monotherapy in a randomized outcome-driven secondary stroke prevention trial.
Topics: Humans; Lactones; Platelet Aggregation Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 26860124
DOI: 10.1177/1747493016632253 -
Best Practice & Research. Clinical... Jun 2018There are several new anticoagulants on the market that will impact perioperative care, including the use of these anticoagulant drugs in the setting of regional... (Review)
Review
There are several new anticoagulants on the market that will impact perioperative care, including the use of these anticoagulant drugs in the setting of regional anesthesia. The ideal pharmacological agent would prevent pathological thrombosis and allow for a normal response to vascular injury to limit bleeding. At present, all antithrombotic agents have increased bleeding risk as their main side effect. We describe the different categories of drugs, e.g., antiplatelet, anticoagulant, and thrombolytic, with particular emphasis on the new drugs that have been introduced into the market. These agents can be evaluated by a number of methods including low-, medium-, or high-risk procedures and guidelines and best practice standards that have been published regarding the amount of time to wait after stopping the medication and before performing a procedure, e.g., the American Society of Regional Anesthesia and Pain Medicine recommendations. The present investigation will also describe new reversal agents for anticoagulants and the implications of all these drugs for regional anesthesia.
Topics: Anticoagulants; Hemorrhage; Humans; Narcotic Antagonists; Perioperative Care; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 30322457
DOI: 10.1016/j.bpa.2018.06.008 -
Current Pharmaceutical Design 2018Acetylsalicylic acid, clopidogrel and cilostazol are well-established agents inhibiting the normal function of platelets with known advantages and limitations. The... (Review)
Review
BACKGROUND
Acetylsalicylic acid, clopidogrel and cilostazol are well-established agents inhibiting the normal function of platelets with known advantages and limitations. The development of novel antiplatelet agents aims to provide equal or superior outcomes for patients and simultaneously minimize side effects.
OBJECTIVE
The aim of this manuscript is to review the latest data on the use of novel antiplatelet agents in vascular patients.
METHOD
Based on our 2016 review, a further search in the English medical literature has yielded a number of publications on cangrelor, prasugrel, ticagrelor, vorapaxar and a number of other - still experimental - agents (Ir- 6, UBO-QIC, W1, revacept and YM-254890).
RESULTS
Recently published data have not altered the use and indications of cangrelor, prasugrel and vorapaxar; all of them now approved by both FDA and EMA. The EUCLID trial has recently provided valuable data on the clinical use of ticagrelor, although results regarding vascular patients and administration of ticagrelor are still under scrutiny. Vorapaxar remains the only novel antiplatelet that is approved for PAD. Randomized control trials that focus on vascular patients are necessary to establish the safety and efficacy of these novel agents. Despite their positive initial results, most novel experimental antiplatelets are still in early development, thus in preclinical or early clinical phases of their trials. Research on three novel antiplatelets is currently discontinued (atopaxar, darexaban and elinogrel).
CONCLUSION
Vorapaxar remains the only novel antiplatelet that is approved for PAD. Other novel antiplatelets demonstrate positive results, but further studies focused on vascular patients are necessary. Novel experimental antiplatelets are still in the early phases of the clinical and preclinical studies.
Topics: Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Drugs, Investigational; Humans; Molecular Structure; Platelet Aggregation Inhibitors; Vascular Diseases
PubMed: 30585537
DOI: 10.2174/1381612825666181226144129 -
Analytical and Bioanalytical Chemistry Jan 2022Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known...
Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known complex cardiovascular diseases driven by platelet and/or coagulation activity, the need of more than one antithrombotic agent is inevitable. However, combining drugs with different mechanisms of action enhances risk of bleeding. Dual anticoagulant and antiplatelet (APAC), a novel semisynthetic antithrombotic molecule, provides both anticoagulant and antiplatelet properties in preclinical studies. APAC is entering clinical studies with this new exciting approach to manage cardiovascular diseases. For a better understanding of the biological function of APAC, comprehensive knowledge of its structure is essential. In this study, atomic force microscopy (AFM) was used to characterize APAC according to its structure and to investigate the molecular interaction of APAC with von Willebrand factor (VWF), since specific binding of APAC to VWF could reduce platelet accumulation at vascular injury sites. By the optimization of drop-casting experiments, we were able to determine the volume of an individual APAC molecule at around 600 nm, and confirm that APAC forms multimers, especially dimers and trimers under the experimental conditions. By studying the drop-casting behavior of APAC and VWF individually, we depictured their interaction by using an indirect approach. Moreover, in vitro and in vivo conducted experiments in pigs supported the AFM results further. Finally, the successful adsorption of APAC to a flat gold surface was confirmed by using photothermal-induced resonance, whereby attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) served as a reference method.
Topics: Anticoagulants; Heparin; Humans; Microscopy, Atomic Force; Platelet Aggregation Inhibitors; Proteoglycans; Spectroscopy, Fourier Transform Infrared
PubMed: 34773471
DOI: 10.1007/s00216-021-03765-y -
Clinical Medicine (London, England) Apr 2016Platelets play a very important role in physiological haemostasis and thrombus formation. Platelet aggregation is the key pathophysiological factor in the development of... (Review)
Review
Platelets play a very important role in physiological haemostasis and thrombus formation. Platelet aggregation is the key pathophysiological factor in the development of arterial ischaemic events, including coronary artery disease, cerebrovascular accidents and peripheral arterial disease. As such, antiplatelet therapy plays a very important role in preventing recurrent events in the individuals who are affected by one of these conditions. Until recently, the repertoire of antiplatelet therapy was limited to aspirin and clopidogrel. However, this landscape has changed dramatically with the advent of newer and more potent agents, prasugrel and ticagrelor and also the glycoprotein IIb/IIIa antagonists. This armamentarium is likely to expand further with the advent of protease-activated receptor-1 antagonists and the intravenous cangrelor. This review summarises the different agents available and some practical considerations for their use from a general physician's perspective.
Topics: Adenosine; Clopidogrel; General Practitioners; Humans; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine
PubMed: 27037385
DOI: 10.7861/clinmedicine.16-2-152 -
Pharmacology Research & Perspectives Dec 2020Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The... (Review)
Review
Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.
Topics: Animals; Clopidogrel; Drug Monitoring; Humans; Pharmacogenetics; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Systems; Thrombelastography
PubMed: 33200888
DOI: 10.1002/prp2.686 -
The Senior Care Pharmacist Jan 2022This case study reviews appropriate antiplatelet treatment options for an older patient post-myocardial infarction and stent placement. This case investigates the...
This case study reviews appropriate antiplatelet treatment options for an older patient post-myocardial infarction and stent placement. This case investigates the benefits and risks associated with antiplatelet agents in older people and what patient- and drug-specific factors, such as adverse effects and drug interactions, to consider when choosing treatment.
Topics: Aged; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors
PubMed: 34953509
DOI: 10.4140/TCP.n.2022.17 -
Stroke Sep 2017Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis.
METHODS
We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model.
RESULTS
Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit.
CONCLUSIONS
Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke.
Topics: Adenosine; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Proportional Hazards Models; Recurrence; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine; Treatment Failure
PubMed: 28701574
DOI: 10.1161/STROKEAHA.117.017895 -
American Journal of Health-system... Oct 2015The safety and efficacy of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in the setting of secondary stroke prevention are reviewed. (Review)
Review
PURPOSE
The safety and efficacy of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in the setting of secondary stroke prevention are reviewed.
SUMMARY
Antiplatelet therapy has been shown to reduce the risk of numerous vascular events, especially in the setting of secondary prevention. DAPT with aspirin and another antiplatelet agent such as clopidogrel, prasugrel, or ticagrelor has become the main stay of acute coronary syndrome (ACS) management. The underlying pathophysiologies of ACS, ischemic stroke, and transient ischemic attack (TIA) are similar. In the setting of ACS, DAPT has clearly been shown to improve outcomes over single antiplatelet therapy for up to 12 months after the ischemic event. However, the role for DAPT in the setting of ischemic stroke and TIA is less clear. The MATCH, CHARISMA, and SPS3 studies demonstrated that DAPT was associated with increased bleeding compared with single antiplatelet therapy without an appreciable reduction in ischemic events. Early initiation of DAPT proved beneficial in reducing future ischemic events in the FASTER and CHANCE trials; however, these trials did not provide enough evidence to recommend the routine use of DAPT in secondary stroke prevention, and current guidelines recommend against such therapy. DAPT with aspirin and clopidogrel appears to be effective only for patients with minor stroke or TIA when started within 24 hours of the ischemic event and continued for a maximum of 21 days.
CONCLUSION
Currently available evidence does not substantiate the widespread use of long-term aspirin with clopidogrel for the secondary prevention of ischemic stroke or TIA.
Topics: Aspirin; Atherosclerosis; Blood Platelets; Clopidogrel; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Severity of Illness Index; Stroke; Ticlopidine; Time Factors
PubMed: 26386103
DOI: 10.2146/ajhp140804