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Trends in Cardiovascular Medicine May 2020Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor agent, is the cornerstone treatment after percutaneous coronary intervention for acute coronary... (Review)
Review
Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor agent, is the cornerstone treatment after percutaneous coronary intervention for acute coronary syndrome. Based on randomized clinical trial using aspirin and clopidogrel, a DAPT duration of 12 months has been recommended after an acute coronary syndrome. Despite the development of more potent antiplatelet agents (i.e. prasugrel and ticagrelor) and the reduction in ischemic recurrences after acute coronary syndrome, 12 months DAPT currently remains the gold standard. However, a significant proportion of patients experience recurrent ischemic events beyond the first 12 months after an acute coronary syndrome. Meanwhile, with more effective antiplatelet agent, bleeding has become a major safety concern on DAPT. Therefore, the ischemic and bleeding risk balance is central considering the duration of DAPT after an acute coronary syndrome. This review aims to report the evidence for an optimization and individualization of DAPT duration after an acute coronary syndrome.
Topics: Acute Coronary Syndrome; Decision Support Techniques; Drug Administration Schedule; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 31182263
DOI: 10.1016/j.tcm.2019.05.008 -
Molecules (Basel, Switzerland) Sep 2022Some fruits and vegetables, rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, may inhibit platelet activation pathways and therefore reduce... (Review)
Review
Some fruits and vegetables, rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, may inhibit platelet activation pathways and therefore reduce the risk of suffering from CVD when consumed regularly. Stuntz (Maqui) is a shrub or tree native to Chile with outstanding antioxidant activity, associated with its high content in anthocyanins, polyphenols, and flavonoids. Previous studies reveal different pharmacological properties for this berry, but its cardioprotective potential has been little studied. Despite having an abundant composition, and being rich in bioactive products with an antiplatelet role, there are few studies linking this berry with antiplatelet activity. This review summarizes and discusses relevant information on the cardioprotective potential of Maqui, based on its composition of bioactive compounds, mainly as a nutraceutical antiplatelet agent. Articles published between 2000 and 2022 in the following bibliographic databases were selected: PubMed, ScienceDirect, and Google Scholar. Our search revealed that Maqui is a promising cardiovascular target since extracts from this berry have direct effects on the reduction in cardiovascular risk factors (glucose index, obesity, diabetes, among others). Although studies on antiplatelet activity in this fruit are recent, its rich chemical composition clearly shows that the presence of chemical compounds (anthocyanins, flavonoids, phenolic acids, among others) with high antiplatelet potential can provide this berry with antiplatelet properties. These bioactive compounds have antiplatelet effects with multiple targets in the platelet, particularly, they have been related to the inhibition of thromboxane, thrombin, ADP, and GPVI receptors, or through the pathways by which these receptors stimulate platelet aggregation. Detailed studies are needed to clarify this gap in the literature, as well as to specifically evaluate the mechanism of action of Maqui extracts, due to the presence of phenolic compounds.
Topics: Adenosine Diphosphate; Anthocyanins; Antioxidants; Elaeocarpaceae; Flavonoids; Fruit; Glucose; Plant Extracts; Platelet Aggregation Inhibitors; Polyphenols; Thrombin; Thromboxanes
PubMed: 36234679
DOI: 10.3390/molecules27196147 -
Journal of Thrombosis and Haemostasis :... May 2017Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated... (Review)
Review
Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.
Topics: Adenine; Animals; Anticoagulants; Antineoplastic Agents; Blood Coagulation; Blood Platelets; Drug Interactions; Drug Substitution; Hemorrhage; Humans; Piperidines; Platelet Aggregation Inhibitors; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Risk Assessment; Risk Factors; Signal Transduction
PubMed: 28182323
DOI: 10.1111/jth.13651 -
Cardiovascular Therapeutics 2009The antiplatelet drug prasugrel is one of the new generations of thienopyridines, drugs that inhibit the platelet P2Y(12) receptor. It is becoming clear that there is... (Review)
Review
The antiplatelet drug prasugrel is one of the new generations of thienopyridines, drugs that inhibit the platelet P2Y(12) receptor. It is becoming clear that there is variability in individual responses to antiplatelet agents such as clopidogrel, which may limit their efficacy and widespread utility. A number of controversies remain, such as varied definitions of "nonresponders" to antiplatelet therapy, the optimal means of assessing platelet function, and the potential capacity of in vivo platelet function studies to predict future clinical events. Prasugrel provides more rapid and consistent platelet inhibition than does clopidogrel, yet its clinical utility is under scrutiny. We aim to review the available data evaluating the efficacy and safety of this novel antiplatelet agent.
Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Animals; Blood Platelets; Evidence-Based Medicine; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Thiophenes
PubMed: 19689619
DOI: 10.1111/j.1755-5922.2009.00086.x -
BMC Neurology Jun 2022The present strategies regarding poststent management for cerebral venous sinus stenosis (CVSS) are inconsistent. Herein, we compared the safety and efficacy of oral... (Observational Study)
Observational Study
BACKGROUND AND PURPOSE
The present strategies regarding poststent management for cerebral venous sinus stenosis (CVSS) are inconsistent. Herein, we compared the safety and efficacy of oral anticoagulants (OACs) plus single antiplatelet therapy and dual antiplatelet therapy for CVSS poststenting.
METHODS
A real-world observational study conducted from January 2009 through October 2019 enrolled patients who were diagnosed with CVSS and received stenting. Patients were divided into two groups according to the management they received poststenting. Group 1: OACs plus a single antiplatelet agent (clopidogrel 75 mg or aspirin 100 mg) and Group 2: dual antiplatelet therapy (clopidogrel 75 mg plus aspirin 100 mg). The safety (such as major or minor bleeding or venous thrombosis) and efficacy (the incidences of cerebral venous sinus restenosis, intrastent thrombosis, or stent displacement) of the two groups were compared.
RESULTS
There were a total of 110 eligible patients in the final analysis, including 79 females and 31 males with a mean age of 43.42 ± 13.23 years. No major bleeding or venous thrombosis occurred in either of the two groups. Two minor bleeding events occurred in group 2 (one with subcutaneous bleeding points in both lower limbs, another with submucosal bleeding in the mouth), whereas no bleeding events occurred in Group 1. In addition, at the 1-year follow-up, one case of intraluminal restenosis and two cases of in-stent thrombi occurred in Group 2, while none occurred in Group 1. Neither stenosis at stent-adjacent segments nor stent migration was detected in either group during the 1-year following stent placement.
CONCLUSION
OACs plus single antiplatelet therapy and dual antiplatelet therapy alone are both safe and efficacious management strategies after CVSS stent placement. The former may have more advantages than the latter for inhibiting intrastent thrombosis. However, further research by larger, multicenter clinical trials is needed.
Topics: Adult; Anticoagulants; Aspirin; Clopidogrel; Constriction, Pathologic; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Thrombosis; Treatment Outcome
PubMed: 35668360
DOI: 10.1186/s12883-022-02731-0 -
Toxicon : Official Journal of the... Dec 2010Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sand flies, fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules that... (Review)
Review
Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sand flies, fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules that counteract hemostasis in a redundant and synergistic manner. This review discusses recent progress in the identification of salivary inhibitors of platelet aggregation, their molecular characterization, and detailed mechanism of action. Diversity of inhibitors is remarkable, with distinct families of proteins characterized as apyrases that enzymatically degrade ADP or as collagen-binding proteins that prevent its interaction with vWF, or platelet integrin α2β1 or GPVI. Molecules that bind ADP, TXA(2), epinephrine, or serotonin with high affinity have also been cloned, expressed, and their structure determined. In addition, a repertoire of antithrombins and an increasingly number of RGD and non-RGD disintegrins targeting platelet αIIbβ3 have been reported. Moreover, metalloproteases with fibrinogen(olytic) activity and PAF phosphorylcholine hydrolase are enzymes that have been recruited to the salivary gland to block platelet aggregation. Platelet inhibitory prostaglandins, lysophosphatydilcholine, adenosine, and nitric oxide (NO)-carrying proteins are other notable examples of molecules from hematophagous salivary secretions (herein named sialogenins) with antihemostatic properties. Sialogenins have been employed as tools in biochemistry and cell biology and also display potential therapeutic applications.
Topics: Animals; Apyrase; Arthropods; Feeding Behavior; Insect Proteins; Models, Biological; Molecular Sequence Data; Platelet Aggregation Inhibitors; Protein Structure, Tertiary; Salivary Glands; Sequence Alignment
PubMed: 20035779
DOI: 10.1016/j.toxicon.2009.12.003 -
Cardiovascular Drugs and Therapy Dec 2009Non-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and... (Review)
Review
INTRODUCTION
Non-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and mortality.
DISCUSSION
The key role of platelet-mediated thrombosis in the pathogenesis of NSTE ACS is confirmed by the proven clinical benefits of antiplatelet agents (aspirin and a P2Y(12) adenosine diphosphate [ADP] receptor antagonist) in this setting. Despite the documented advantages and broad use of antiplatelet therapy, the long-term morbidity and mortality rates remain significant, and the bleeding risk remains substantial. Residual risk can be attributed, at least in part, to the fact that thrombosis continues in the presence of current treatments because aspirin and P2Y(12) ADP receptor antagonists each block only one of multiple platelet activation pathways, and thus do not impact other platelet activation pathways, such as the one triggered by interaction of thrombin with protease-activated receptor (PAR)-1, thereby exposing patients to continued accumulation of thrombotic events.
CONCLUSION
These considerations suggest that novel therapies with a different mechanism of action, when used in combination with current antiplatelet agents, may provide more comprehensive inhibition of platelet activation and additional reductions in morbidity and mortality, potentially without incremental bleeding risk.
Topics: Acute Coronary Syndrome; Administration, Oral; Aspirin; Chronic Disease; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Thrombin; Risk Factors
PubMed: 19890703
DOI: 10.1007/s10557-009-6204-5 -
PloS One 2015There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.
There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46-0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58-0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58-0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61-0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46-0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23-39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22-2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05-2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.
Topics: Amputation, Surgical; Databases, Factual; Female; Hemorrhage; Humans; Leg; Male; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Stroke
PubMed: 26274912
DOI: 10.1371/journal.pone.0135692 -
Medecine Sciences : M/S Apr 2020Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet... (Review)
Review
Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet drugs is a priority in the fight against cardiovascular diseases-associated mortality. Aspirin and thienopyridine-based P2Y12 inhibitors are the main drugs currently used. These molecules target the initiation of platelets activation and are responsible for a moderate inhibitory action. Other antiplatelet agents, as glycoprotein (GP) IIb/IIIa antagonists, inhibit platelet aggregation independently of initial activation-associated pathways, but are responsible for increased hemorrhagic events. Regarding each antiplatelet agent's specific characteristics, the prescription of these drugs must take into account the type of cardiovascular event, the age of the patient, the past medical history, and the potential hemorrhagic adverse events. Thus, there is a need for the development of new molecules with a more targeted effect, maintaining optimal efficiency but with a reduction of the hemorrhagic risk, which is the principal limitation of these treatments.
Topics: Aspirin; Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Hemorrhage; Humans; Molecular Targeted Therapy; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Risk Factors; Therapies, Investigational
PubMed: 32356711
DOI: 10.1051/medsci/2020061 -
Arteriosclerosis, Thrombosis, and... May 2019Objective- ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This... (Randomized Controlled Trial)
Randomized Controlled Trial
Objective- ACT017 is a novel, first in class, therapeutic antibody to platelet GPVI (glycoprotein VI) with potent and selective antiplatelet effects. This first-in-human, randomized, placebo-controlled phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT017 in healthy subjects. Approach and Results- Six cohorts of 8 healthy male and female subjects each received ascending single doses of ACT017 (n=6) or placebo (n=2) as a 6-hour intravenous infusion, with ¼ of the total dose administered within 15 minutes and the rest of the dose (¾ of the total dose) administered within 5 hours and 45 minutes. The 6 investigated doses ranged from 62.5 to 2000 mg. All doses of ACT017 were well tolerated, and no serious adverse events occurred during the study. None of the subjects reported an infusion site reaction. Template bleeding time was not affected in a clinically significant manner by any of the ACT017 doses. Plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, increased linearly with the dose received as were the established pharmacokinetics values. There was no change in the platelet count, platelet GPVI expression assessed by flow cytometry, or plasma levels of soluble GPVI assessed by ELISA. In contrast, administration of ACT017 inhibited collagen-induced platelet aggregation measured by light transmission aggregometry on platelet-rich plasma, and the extent and duration of the effect were dose-dependent. Conclusions- The novel antiplatelet agent ACT017 has consistent pharmacokinetic/pharmacodynamic properties and favorable safety and tolerability profiles warranting further clinical development.
Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Patient Safety; Platelet Aggregation Inhibitors
PubMed: 31017822
DOI: 10.1161/ATVBAHA.118.312314