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BioMed Research International 2022Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and...
Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLC2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.
Topics: Animals; Blood Platelets; Collagen; Mice; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinazolines; Thrombosis
PubMed: 35937403
DOI: 10.1155/2022/4893859 -
Journal of Thrombosis and Haemostasis :... Jun 2015There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response... (Review)
Review
There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response may be attributable to genetic variants. Thus, pharmacogenetics may help to accurately predict response to cardiovascular disease (CVD) therapies in order to maximize drug efficacy, minimize drug toxicity, and to tailor personalized care for these patients. Although the clinical utility of pharmacogenetics is promising, its adoption in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies. Thus, this review focuses on the genetic determinants of commonly used platelet antagonists and anticoagulants including aspirin, clopidogrel, dabigatran, and warfarin. We also explore the clinical translation of pharmacogenetics in the management of patients with CVD.
Topics: Animals; Anticoagulants; Biotransformation; Cardiovascular Diseases; Drug Resistance; Genotype; Humans; Pharmacogenetics; Phenotype; Platelet Aggregation Inhibitors; Precision Medicine; Risk Factors; Treatment Outcome
PubMed: 26149037
DOI: 10.1111/jth.12924 -
The Cochrane Database of Systematic... Jul 2007Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived... (Review)
Review
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, and low dose aspirin in particular, might prevent or delay the development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia, and to those with established pre-eclampsia.
SEARCH STRATEGY
This review drew on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The Cochrane Controlled Trials Register was also searched, The Cochrane Library 1999 Issue 1, Embase was searched from 1994-1999 and hand searches were performed of the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia, and those with pre-eclampsia before delivery. Women treated postpartum were excluded. Interventions were any comparisons of an antiplatelet agent (such as low dose aspirin or dipyridamole) with either placebo or no antiplatelet agent.
DATA COLLECTION AND ANALYSIS
Assessment of trials for inclusion in the review and extraction of data was performed independently and unblinded by two reviewers. Data were entered into the Review Manager software and double checked.
MAIN RESULTS
Forty two trials involving over 32,000 women were included in this review, with 30,563 women in the prevention trials. There is a 15% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents [32 trials with 29,331 women; relative risk (RR) 0.85, 95% confidence interval (0.78, 0.92); Number needed to treat (NNT) 89, (59, 167)]. This reduction is regardless of risk status at trial entry or whether a placebo was used, and irrespective of the dose of aspirin or gestation at randomisation.Twenty three trials (28,268 women) reported preterm delivery. There is a small (8%) reduction in the risk of delivery before 37 completed weeks [RR 0.92, (0.88, 0.97); NNT 72 (44, 200)]. Baby deaths were reported in 30 trials (30,093 women). Overall there is a 14% reduction in baby deaths in the antiplatelet group [RR 0.86, (0.75, 0.98); NNT 250 (125, >10000)]. Small for gestational age babies were reported in 25 trials (20,349 women), with no overall difference between the groups, RR 0.92, (0.84, 1.01). There were no significant differences between treatment and control groups in any other measures of outcome. Five trials compared antiplatelet agents with placebo or no antiplatelet agent for the treatment of pre-eclampsia. There are insufficient data for any firm conclusions about the possible effects of these agents when used for treatment of pre-eclampsia.
AUTHORS' CONCLUSIONS
Antiplatelet agents, in this review largely low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.
Topics: Aspirin; Female; Humans; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 17636639
DOI: 10.1002/14651858.CD000492.pub2 -
BMJ Case Reports Jun 2021Drug-induced immune thrombocytopaenia (DITP) is a type of thrombocytopaenia caused by medications. It is one of the common causes of unexplained thrombocytopaenia. It is...
Drug-induced immune thrombocytopaenia (DITP) is a type of thrombocytopaenia caused by medications. It is one of the common causes of unexplained thrombocytopaenia. It is caused by the formation of autoantibodies against a particular drug and is commonly observed with medications like heparin and beta-lactam antibiotics. One of the rare causes of DITP is eptifibatide, a widely used antiplatelet agent for pretreatment in cardiac catheterisation. These patients can be asymptomatic or develop complications like skin bruising, epistaxis and even intracranial haemorrhage. We present a case of a 64-year-old man who developed eptifibatide-induced profound thrombocytopaenia leading to extensive skin bruising. He was treated with platelet transfusions followed by prompt improvement in platelet count.
Topics: Eptifibatide; Heparin; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Thrombocytopenia
PubMed: 34127501
DOI: 10.1136/bcr-2021-241594 -
European Journal of Vascular and... May 2004Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept... (Review)
Review
BACKGROUND
Aspirin is effective at reducing the cardiovascular event rate in defined patient groups. The introduction of antiplatelet therapies other than aspirin and the concept of aspirin resistance have led to critical reappraisal of current treatment. This review aims to clarify the evidence for aspirin resistance in patients with atherosclerosis.
METHODS
Medline search was performed to identify publications concerned with antiplatelet effects of aspirin and failure of aspirin therapy. Manual cross referencing was also performed.
RESULTS AND CONCLUSION
Wide variations in the rate of aspirin resistance (5.5-75%) have been reported. The lack of consensus on an appropriate definition and the number of different tests used to investigate aspirin resistance needs to be addressed. There are few studies where the primary aim was to document aspirin resistance or aspirin non-response. Further work should aim to investigate if aspirin resistance is clinically important and, if it is, what treatments may be beneficial to the at risk patient.
Topics: Arteriosclerosis; Aspirin; Drug Resistance; Humans; Platelet Aggregation Inhibitors
PubMed: 15079767
DOI: 10.1016/j.ejvs.2003.12.025 -
Journal of the American College of... Sep 2021Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease.... (Review)
Review
Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease. The ischemic benefit of DAPT is partially offset by its increased bleeding risk, with intracranial hemorrhage (ICH) being the most serious complication. Although uncommon (0.2%-0.3% annually), its cumulative burden can be substantial given the number of patients afflicted by cardiovascular disease worldwide. Patients with a history of stroke or transient ischemic attack harbor a particularly high risk for ICH when treated with DAPT. Prediction rules may assist clinicians when weighing the risk/benefit ratio of prescribing DAPT for patients with stroke/transient ischemic attack in the nonacute, ambulatory setting. Currently, there are no reversal agents that can rapidly and effectively reverse the effect of P2Y inhibitors in routine practice, although a reversal agent for ticagrelor is under clinical investigation.
Topics: Dual Anti-Platelet Therapy; Humans; Intracranial Hemorrhages; Platelet Aggregation Inhibitors; Risk Factors
PubMed: 34556323
DOI: 10.1016/j.jacc.2021.07.048 -
Medicina (Kaunas, Lithuania) Jan 2021Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic... (Review)
Review
Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.
Topics: Aspirin; Biological Availability; Clopidogrel; Drug Interactions; Drug Resistance; Humans; Ischemic Stroke; Kidney Failure, Chronic; Metabolic Syndrome; Pharmacogenomic Variants; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Risk Assessment; Secondary Prevention; Smoking; Stroke
PubMed: 33435185
DOI: 10.3390/medicina57010059 -
The New England Journal of Medicine Jul 2007Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear.
METHODS
We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes.
RESULTS
A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).
CONCLUSIONS
In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aspirin; Atherosclerosis; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin
PubMed: 17634457
DOI: 10.1056/NEJMoa065959 -
ACS Applied Materials & Interfaces Jan 2019Two major challenges faced by medical devices are thrombus formation and infection. In this work, surface-tethered nitric oxide (NO)-releasing molecules are presented as...
Two major challenges faced by medical devices are thrombus formation and infection. In this work, surface-tethered nitric oxide (NO)-releasing molecules are presented as a solution to combat infection and thrombosis. These materials possess a robust NO release capacity lasting ca. 1 month while simultaneously improving the nonfouling nature of the material by preventing platelet, protein, and bacteria adhesion. NO's potent bactericidal function has been implemented by a facile surface covalent attachment method to fabricate a triple-action coating-surface-immobilized S-nitroso- N-acetylpenicillamine (SIM-S). Comparison of NO loading amongst the various branching configurations is shown through the NO release kinetics over time and the cumulative NO release. Biological characterization is performed using in vitro fibrinogen and Staphylococcus aureus assays. The material with the highest NO release, SIM-S2, is also able to reduce protein adhesion by 65.8 ± 8.9% when compared to unmodified silicone. SIM-S2 demonstrates a 99.99% (i.e., ∼4 log) reduction for S. aureus over 24 h. The various functionalized surfaces significantly reduce platelet adhesion in vitro, for both NO-releasing and non-NO-releasing surfaces (up to 89.1 ± 0.9%), demonstrating the nonfouling nature of the surface-immobilized functionalities. The ability of the SIM-S surfaces to retain antifouling properties despite gradual depletion of the bactericidal source, NO, demonstrates its potential use in long-term medical implants.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Adhesion; Blood Platelets; Humans; Nitric Oxide; Platelet Aggregation Inhibitors; S-Nitroso-N-Acetylpenicillamine; Staphylococcus aureus; Surface Properties
PubMed: 30607929
DOI: 10.1021/acsami.8b16819 -
Clinical Cardiology Sep 1999New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in... (Review)
Review
BACKGROUND
New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in patients with atherosclerotic vascular disease have been performed.
HYPOTHESIS
An updated systematic review and evidence-based guidelines for the appropriate selection of antiplatelet drugs may be beneficial to physicians and healthcare organizations attempting to create or update current clinical practice guidelines or clinical pathways aimed at caring for these patients.
METHODS
(1) A systematic review of the recent literature on the relative efficacy and safety of aspirin, ticlopidine, and clopidogrel was undertaken; (2) an evidence-based, expert panel approach using a modified Delphi technique to create explicit guidelines for prescribing antiplatelet therapy was instituted; and (3) the recommendations of an expert panel were summarized.
RESULTS
Consensus guidelines were developed for the utilization of aspirin, ticlopidine, or clopidogrel for the prevention of ischemic events in patients with manifestations of atherosclerotic vascular disease (prior myocardial infarction, prior ischemic stroke, or established peripheral arterial disease) who are at increased risk for recurrent ischemic events. Based on efficacy and safety, clopidogrel was recommended as the drug of choice for patients with established peripheral arterial disease; aspirin or clopidogrel should be considered in patients with prior myocardial infarction (with clopidogrel favored for patients who have had a recurrent event while on aspirin or in whom aspirin is contraindicated); aspirin or clopidogrel should be considered as first-line treatment in patients with prior ischemic (nonhemorrhagic) stroke--however, clopidogrel is the favored drug in patients in whom other antiplatelet drugs are either contraindicated or who have had recurrent events while on therapy.
CONCLUSIONS
Myocardial infarction, ischemic stroke, and peripheral arterial disease are all clinical manifestations of the same underlying disease process (atherosclerosis), with thrombus formation on the disrupted atherosclerotic plaque (atherothrombosis) being a common precipitating factor of ischemic events in patients suffering from these disorders. An evidence-based approach was used to develop a practice guideline, based on available published evidence, for the appropriate utilization of antiplatelet agents (aspirin, ticlopidine, or clopidogrel). These guidelines may be of use to multidisciplinary teams wishing to create or update clinical guidelines or clinical pathways which address the care of patients with atherosclerotic vascular disease. New antiplatelet agents such as clopidogrel may be more effective and associated with lower risk of selected adverse effects (such as gastrointestinal distress, gastrointestinal hemorrhage, and neutropenia) than those previously used to prevent thrombus formation in the setting of atherosclerotic arterial disease. Combination antiplatelet therapy is being evaluated as an option for those patients who experience recurrent events on a single antiplatelet agent.
Topics: Algorithms; Arteriosclerosis; Aspirin; Brain Ischemia; Clinical Trials as Topic; Clopidogrel; Critical Pathways; Evidence-Based Medicine; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk; Ticlopidine
PubMed: 10486695
DOI: 10.1002/clc.4960220905