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International Journal of Molecular... Mar 2022Platelets are at the forefront of human health and disease following the advances in their research presented in past decades. Platelet activation, their most crucial... (Review)
Review
Platelets are at the forefront of human health and disease following the advances in their research presented in past decades. Platelet activation, their most crucial function, although beneficial in the case of vascular injury, may represent the initial step for thrombotic complications characterizing various pathologic states, primarily atherosclerotic cardiovascular diseases. In this review, we initially summarize the structural and functional characteristics of platelets. Next, we focus on the process of platelet activation and its associated factors, indicating the potential molecular mechanisms involving inflammation, endothelial dysfunction, and miRs. Finally, an overview of the available antiplatelet agents is being portrayed, together with agents possessing off-set platelet-inhibitory actions, while an extensive presentation of drugs under investigation is being given.
Topics: Blood Platelets; Humans; Pharmaceutical Preparations; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 35328719
DOI: 10.3390/ijms23063301 -
Current Pharmaceutical Design 2017Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes... (Review)
Review
Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration. In this review, we critically discuss their main pharmacodynamic and pharmacokinetic characteristics as well as recent advances in daily clinical practice.
Topics: Anticoagulants; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 28120727
DOI: 10.2174/1381612823666170124141806 -
Current Atherosclerosis Reports Jul 2015Stroke recurrence is common in the early period after a cerebral ischemic event. Treatment with an antiplatelet agent is recommended to reduce recurrent stroke and death... (Review)
Review
Stroke recurrence is common in the early period after a cerebral ischemic event. Treatment with an antiplatelet agent is recommended to reduce recurrent stroke and death in patients with a non-cardioembolic ischemic stroke and transient ischemic attack. Compared to monotherapy, dual antiplatelet therapy has more robust inhibition of platelet activation but a higher risk of systemic bleeding and intracranial hemorrhage. Randomized controlled trials and meta-analyses suggest that short-term use of dual antiplatelet treatment initiated early after ischemic stroke and TIA reduces the risk of recurrent stroke and major vascular events without significantly increasing the hemorrhagic complication rates, particularly in those with large-vessel disease, while long-term dual antiplatelet treatment increases the risk of systemic and intracranial hemorrhage over time, offsetting any potential benefit. Until further data becomes available, clinicians should carefully assess this risk and benefit in each case and continually reevaluate the need for prolonged dual antiplatelet therapy.
Topics: Brain Ischemia; Drug Therapy, Combination; Humans; Intracranial Hemorrhages; Platelet Activation; Platelet Aggregation Inhibitors; Stroke
PubMed: 25990661
DOI: 10.1007/s11883-015-0515-8 -
Expert Opinion on Pharmacotherapy Oct 2018Stroke not only causes critical disability and death but is also a cause of anxiety with the possibility of secondary cardiovascular events including secondary ischemic... (Review)
Review
Stroke not only causes critical disability and death but is also a cause of anxiety with the possibility of secondary cardiovascular events including secondary ischemic stroke. Indeed, patients with a history of previous stroke have a high rate of stroke recurrence, indicating the clinical importance of secondary stroke prevention. Area of covered: This review provides an overview of the pooled evidence for cilostazol's use in the management of secondary stroke prevention. Among the various antiplatelet agents that are available, aspirin is the most frequently used agent worldwide for the prevention of secondary stroke. Cilostazol, a selective phosphodiesterase (PDE) 3A inhibitor, is used worldwide for the treatment of patients with intermittent claudication. However, in Asia, cilostazol is recommended and used in practice for secondary stroke prevention. Expert opinion: The authors believe that cilostazol could be used for secondary stroke prevention not only in Asia but worldwide. However, further randomized trials on cilostazol are needed, especially in the US and Europe to better support its case.
Topics: Cerebral Infarction; Cilostazol; Humans; Platelet Aggregation Inhibitors
PubMed: 30212227
DOI: 10.1080/14656566.2018.1515199 -
Journal of Thrombosis and Thrombolysis Apr 2018Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen... (Review)
Review
Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39-55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.
Topics: Anticoagulants; Drug Therapy, Combination; Hemorrhage; Humans; Patient Selection; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 29478128
DOI: 10.1007/s11239-018-1635-0 -
Journal of Thrombosis and Haemostasis :... Oct 2022Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from...
Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.
Topics: Aftercare; Anticoagulants; COVID-19; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Humans; Patient Discharge; Platelet Aggregation Inhibitors; Rivaroxaban
PubMed: 35906716
DOI: 10.1111/jth.15808 -
Methods in Molecular Biology (Clifton,... 2022Platelet activation and aggregation is implicated in all stages of inflammation-related atherosclerosis from the initial steps of endothelial dysfunction and plaque...
Platelet activation and aggregation is implicated in all stages of inflammation-related atherosclerosis from the initial steps of endothelial dysfunction and plaque formation, to plaque rupture and atherothrombotic events, such as acute coronary syndrome, myocardial infarction, and ischemic incidences. Platelet aggregometry assays are the mainstream for evaluating and monitoring platelet reactivity in such conditions and for the investigation of prophylactic and therapeutic approaches. The most established methodology is light transmittance aggregometry (LTA). Here we describe the appropriate preparation of platelet suspensions from human blood and the methodology of LTA-based assays that is used for basic and clinical research for monitoring and evaluating the activities of several thrombotic mediators, as well as determining the dose efficacy and safety of several pharmaceutical and nutraceutical compounds intended for therapeutic and prophylactic interventions for atherosclerosis.
Topics: Atherosclerosis; Blood Platelets; Humans; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests
PubMed: 35237975
DOI: 10.1007/978-1-0716-1924-7_21 -
Expert Opinion on Pharmacotherapy Apr 2015Clopidogrel is an antiplatelet agent widely prescribed for acute coronary syndrome (ACS), and it is activated by the CYP enzyme system to active metabolite. CYP2C19... (Review)
Review
INTRODUCTION
Clopidogrel is an antiplatelet agent widely prescribed for acute coronary syndrome (ACS), and it is activated by the CYP enzyme system to active metabolite. CYP2C19 loss-of-function (LOF) allele(s) affect the responsiveness of clopidogrel, but not the new antiplatelet agents (prasugrel and ticagrelor). We reviewed the pharmacoeconomic studies on genotype-guided use of new antiplatelet agents.
AREAS COVERED
A literature search was conducted between the period of 2000 and 2014. Seven studies including cost-effectiveness and risk-benefit analyses of CYP2C19 genotype-guided antiplatelet therapy in ACS patients were reviewed. Genotype-guided prasugrel was found to be cost-effective when compared with universal antiplatelet therapy in four studies. Three studies showed genotype-guided ticagrelor to be cost-effective in ACS patients with percutaneous coronary intervention (PCI), and universal ticagrelor to be cost-effective in ACS patients. Drug cost of antiplatelet agents and relative risk of the new antiplatelet versus clopidogrel for clinical events were common influential factors of cost-effectiveness analyses.
EXPERT OPINION
All studies in the present review focused on selecting antiplatelet agents for carriers of CYP2C19 LOF allele(s). Cost-effectiveness of genotype-guided use of antiplatelets was demonstrated in high-risk ACS patients.
Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Genotype; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Risk Assessment; Thiophenes; Ticagrelor; Ticlopidine
PubMed: 25660101
DOI: 10.1517/14656566.2015.1013028 -
Current Cardiology Reports Jan 2019The treatment of patients requiring anticoagulation who develop acute coronary syndrome (ACS) and/or require percutaneous coronary intervention (PCI) must balance the... (Review)
Review
The treatment of patients requiring anticoagulation who develop acute coronary syndrome (ACS) and/or require percutaneous coronary intervention (PCI) must balance the reduction in major adverse cardiovascular events, stroke, and major bleeding. The development of direct oral anticoagulants (DOACs) for the treatment of atrial fibrillation has ushered in an era of potential treatment options for these complex patients. PURPOSE OF REVIEW: To review the clinical evidence underlying the use of DOACs for the treatment of patients with atrial fibrillation and ACS or PCI. RECENT FINDINGS: Three trials studied this particular patient population; WOEST showed that dual therapy with warfarin and clopidogrel decreased hemorrhage at 1 year compared with standard triple therapy (19.4 vs. 44.4% HR 0.36; 95% CI 0.26-0.50; P < 0.0001), without increasing thromboembolic events (11.1 vs. 17.6% HR 0.60; 95% CI 0.38-0.94; P = 0.025). PIONEER AF-PCI showed that 10-15 mg rivaroxaban plus P2Y inhibitor for 12 months significantly lowered bleeding rates than standard triple therapy (16.8 vs. 26.7% HR 0.59; 95% CI 0.47-0.76; P < 0.001) and had equivalent rates of MACE. Finally, REDUAL-PCI compared two different doses of dabigatran (110 mg twice daily and 150 mg twice daily) plus P2Y inhibitor with standard triple therapy and reported reduced ISTH bleeding with both doses; HR 0.52 with 110 mg dabigatran (95% CI 0.42-0.63, P < 0.001) and HR 0.72 with 150 mg dabigatran (95% CI 0.58-0.88; P = 0.002). The rate of the composite of thromboembolic events, death, or unplanned revascularizations was similar between pooled dabigatran dual therapy and triple therapy groups (13.7 vs 13.4% HR 1.04; 95% CI 0.84-1.29; P = 0.005). Recent evidence shows that DOACs plus one antiplatelet agent can decrease bleeding in patients with atrial fibrillation undergoing PCI for ACS. Although not powered to detect non-inferiority or superiority, large studies suggest rivaroxaban 10-15 mg plus P2Y inhibitor for 12 months or dabigatran 150 mg twice daily plus P2y12 inhibitor for 12 months will have similar rates of MACE and stent thrombosis as triple therapy. In patients who have contraindications to DOACs, the strategy of INR-adjusted warfarin plus clopidogrel appears to be safer than warfarin plus dual antiplatelet therapy.
Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Treatment Outcome; Warfarin
PubMed: 30637536
DOI: 10.1007/s11886-019-1090-3 -
Annales de Cardiologie Et D'angeiologie Dec 2016Women is a fragile and complex substet of patients, under-represented in clinical trials, but experiencing growing cardiovascular events, with higher mortality, delayed... (Comparative Study)
Comparative Study Review
Women is a fragile and complex substet of patients, under-represented in clinical trials, but experiencing growing cardiovascular events, with higher mortality, delayed presentation, higher bleeding complications and undertreatment with antithrombotic therapies, compared to their male counterparts. Female gender has been associated with enhanced basal platelet reactivity, high residual on-treatment platelet reactivity and various responses to antiplatelet agents. Growing concern on gender-specificity has emerged, including potential difference in women compared with men on the benefits and risks of antiplatelet therapy in primary or secondary prevention and according the antiplatelet agent used. We provide here a review of available data on antiplatelet therapy in women.
Topics: Clinical Trials as Topic; Coronary Thrombosis; Female; Hemorrhage; Humans; Male; Platelet Activation; Platelet Aggregation Inhibitors; Sex Factors
PubMed: 27816174
DOI: 10.1016/j.ancard.2016.10.008