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Clinical Cardiology Oct 2015There is wide variability in prescribing of antiplatelet regimens following transcatheter aortic valve implantation (TAVI). The objective of this review was to evaluate... (Meta-Analysis)
Meta-Analysis Review
There is wide variability in prescribing of antiplatelet regimens following transcatheter aortic valve implantation (TAVI). The objective of this review was to evaluate published and unpublished reports regarding the efficacy and safety of dual antiplatelet therapy (DAPT) compared with a single antiplatelet agent in patients undergoing TAVI. We searched MEDLINE, CENTRAL, Embase, and unpublished sources of literature from inception to December 2014 using terms synonymous with TAVI and DAPT. We included randomized controlled trials (RCTs) and cohort or case-control studies that compared DAPT with a single antiplatelet agent post-TAVI. Four articles met the inclusion criteria (2 RCTs, 2 cohort studies), of which all were deemed to be at high risk of bias, for a total of 662 patients. Compared with a single antiplatelet agent, DAPT did not significantly reduce all-cause mortality (risk ratio: 1.22, 95% confidence interval: 0.72-2.09, I(2) = 0%). Due to selective outcome reporting and variable follow-up, other outcomes of interest could not be meta-analyzed; however, evaluation of individual studies demonstrated no significant reduction in thrombotic events with DAPT and a similar or higher risk of bleeding. Current evidence, though limited by low methodological quality, suggests a lack of benefit and potential harm with DAPT compared with a single antiplatelet agent in patients post-TAVI. Therefore, clinicians should evaluate the use of DAPT in patients post-TAVI on a case-by-case basis until more robust evidence is available to guide practice.
Topics: Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Cardiac Catheterization; Chi-Square Distribution; Drug Therapy, Combination; Female; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Odds Ratio; Platelet Aggregation Inhibitors; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26239886
DOI: 10.1002/clc.22426 -
British Journal of Clinical Pharmacology Oct 2011Glycoprotein (GP) IIb-IIIa antagonists inhibit the aggregation of activated platelets. Three agents are approved for clinical use. In this review, the characteristics of... (Review)
Review
Glycoprotein (GP) IIb-IIIa antagonists inhibit the aggregation of activated platelets. Three agents are approved for clinical use. In this review, the characteristics of each agent, their pharmacodynamic profile, results in pivotal clinical trials and the associated clinical implications are discussed. GP IIb-IIIa antagonists have greatest benefit when used as adjunctive therapy during percutaneous coronary intervention (PCI) when the patient has intra-coronary thrombosis. These agents appear to provide greatest benefit when used in combination with heparin. The clinical niche for parenteral GP IIb-IIIa antagonists is evolving. The rapid onset and offset of GP IIb-IIIa antagonists plus dosing designed to inhibit extensively platelet aggregation differentiates them from oral agents. The contemporary niche appears to include patients in transition, such as individuals requiring emergent PCI before oral agents are fully active and for unstable patients requiring transport to PCI centres, particularly in patients likely to have intracoronary thrombus. Subsequent studies should evaluate the optimal duration of therapy with GP IIb-IIIa antagonists.
Topics: Acute Coronary Syndrome; Blood Platelets; Clinical Trials as Topic; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex
PubMed: 21906121
DOI: 10.1111/j.1365-2125.2010.03879.x -
Journal of Vascular Surgery Apr 2020Prior studies have evaluated the effects of statin and antiplatelet agent (APA) medications on patients with peripheral arterial disease. Although the benefits of statin...
OBJECTIVE
Prior studies have evaluated the effects of statin and antiplatelet agent (APA) medications on patients with peripheral arterial disease. Although the benefits of statin and APA use are well-described, there is a paucity of research into the specific outcomes of patients who are not compliant or those who are unable to take the medication owing to intolerance. Here we examine the outcomes of patients intolerant to statin and APA and compare them with patients who are compliant or noncompliant with these therapies.
METHODS
Patients treated from 2005 to 2018 in the Vascular Quality Initiative registry were included. Patients with missing data or deaths within 30 days of procedure were removed. Patients were considered noncompliant if they were previously prescribed a medication at discharge but were not taking it at 1-year follow-up or if the patient was reported to be noncompliant in the registry. Medication intolerance was defined if listed as "no, for medical reasons," and mortality data were ascertained using the Social Security Death Index, which is regularly cross-referenced to the Vascular Quality Initiative registry.
RESULTS
We identified 105,628 patients who met our inclusion criteria. Statin intolerance was noted in 2.3% at discharge and 2.1% at the 1-year follow-up, with 0.7% listed as intolerant at all stages. Factors associated with increased risk of intolerance to statins included female gender (P = .001), discharge APA intolerance (P = .004), insurance status (non-U.S. insurance) (P < .001), discharge APA noncompliance (P = .019), and discharge angiotensin converting enzyme inhibitor noncompliance (P = .005). Patients who were compliant with statins showed a 91% survival at 5 years vs 87% survival in noncompliant patients and 87% in intolerant patients at 5 years (P < .001). Patients with statin intolerance have a similar survival curve as noncompliant patients across all registry cohorts. Noncompliance with statins was correlated with noncompliance with APA medications (R = 0.16, P < .001). Factors associated with increased risk of statin noncompliance included preoperative ambulatory status (requiring assistance) (P = .039), female sex (P < .001), peripheral vascular intervention (P < .001) or infrainguinal open bypass procedure surgery (P = .001), discharge status (to nursing home) (P = .006) and insurance (self-pay) (P < .001).
CONCLUSIONS
Patients not taking statin and APA medications have a substantially decreased 5-year survival irrespective of the reason for not taking. Importantly, patients noted to be intolerant have a similar survival curve as noncompliant patients across all registry cohorts. Intolerant patients may benefit from attempts to alter statin dose, type (hydrophilic vs lipophilic), or from newer agents such as PCSK9 inhibitors.
Topics: Aged; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medication Adherence; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Survival Rate; Vascular Surgical Procedures
PubMed: 32035776
DOI: 10.1016/j.jvs.2019.07.063 -
Angewandte Chemie (International Ed. in... Sep 2020The first trans-selective cyanoboration reaction of an alkyne, specifically a 1,3-enyne, is described. The reported palladium-catalyzed cyanoboration of 1,3-enynes is...
The first trans-selective cyanoboration reaction of an alkyne, specifically a 1,3-enyne, is described. The reported palladium-catalyzed cyanoboration of 1,3-enynes is site-, regio-, and diastereoselective, and is uniquely enabled by the 1,4-azaborine-based Senphos ligand structure. Tetra-substituted alkenyl nitriles are obtained providing useful boron-dienenitrile building blocks that can be further functionalized. The utility of our method has been demonstrated with the synthesis of Satigrel, an anti-platelet aggregating agent.
Topics: Boranes; Catalysis; Cyanides; Density Functional Theory; Fatty Acids, Monounsaturated; Hydrocarbons; Palladium; Platelet Aggregation Inhibitors; Stereoisomerism
PubMed: 32511855
DOI: 10.1002/anie.202005882 -
International Journal of Molecular... Jun 2018In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high... (Review)
Review
In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high efficacy and low side effects. Cardiovascular diseases (CVDs) are mutually considered as the number one killer globally, and thrombosis is liable for the majority of CVD-related deaths. Platelets, an anuclear and small circulating blood cell, play key roles in hemostasis by inhibiting unnecessary blood loss of vascular damage by making blood clot. Platelet activation also plays a role in cancer metastasis and progression. Nevertheless, abnormal activation of platelets results in thrombosis under pathological settings such as the rupture of atherosclerotic plaques. Thrombosis diminishes the blood supply to the heart and brain resulting in heart attacks and strokes, respectively. While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have motivated their attention on the synthesis of various ruthenium (Ru) complexes due to their prospective therapeutic values. Similarly, our recent studies established that novel ruthenium-based compounds suppressed platelet aggregation via inhibiting several signaling cascades. Our study also described the structure antiplatelet-activity relationship (SAR) of three newly synthesized ruthenium-based compounds. This review summarizes the antiplatelet activity of newly synthesized ruthenium-based compounds with their potential molecular mechanisms.
Topics: Animals; Blood Platelets; Humans; Molecular Targeted Therapy; Organometallic Compounds; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Ruthenium; Thrombosis
PubMed: 29925802
DOI: 10.3390/ijms19061818 -
Pharmacological Research May 2017Cardiovascular disease (CVD) represents the leading cause of death worldwide, and equally affects both sexes although women develop disease at an older age than men. A... (Review)
Review
Cardiovascular disease (CVD) represents the leading cause of death worldwide, and equally affects both sexes although women develop disease at an older age than men. A number of clinical evidence has identified the female sex as an independent factor for poor prognosis, with the rate of mortality and disability following an acute cardiovascular (CV) event being higher in women than men. It has been argued that the different level of platelet reactivity between sexes may account for a different responsiveness to anti-platelet therapy, with consequent important implications on clinical outcomes. However, conclusive evidence supporting the concept of a gender-dependent effectiveness of platelet inhibitors are lacking. On the contrary, sex-related dissimilarities have been evidenced in cardiovascular patients in terms of age of presentation, comorbidities such as obesity, diabetes and renal disease, and a different pharmacological approach to and effectiveness in controlling classical cardiovascular risk factors such as hypertension, glucose profile and lipid dysmetabolism. All these factors could place women at an increased level of cardiovascular risk compared to men, and may concur to an enhanced pro-thrombogenic profile. The purpose of this manuscript is to provide an overview of gender-related differences in cardiovascular treatment, in order to highlight the need to improve the pharmacological prophylaxis adopted in women through a more accurate evaluation of the overall cardiovascular risk profile with consequent establishment of a more effective and targeted anti-thrombotic strategy which is not limited to the use of anti-platelet agents.
Topics: Blood Platelets; Cardiovascular Diseases; Female; Humans; Male; Platelet Aggregation Inhibitors; Prognosis; Sex Characteristics; Sex Factors
PubMed: 28131875
DOI: 10.1016/j.phrs.2017.01.025 -
British Journal of Haematology Apr 2017Gastrointestinal haemorrhage is a common clinical scenario and, in those using antithrombotic agents, the risk is significantly increased. Management of these patients,... (Review)
Review
Gastrointestinal haemorrhage is a common clinical scenario and, in those using antithrombotic agents, the risk is significantly increased. Management of these patients, in terms of initial resuscitation is well established and numerous guidelines exist in this area. However, few studies have addressed the subsequent dilemma of if and when antithrombotic agents should be reintroduced. Consequently, practice is variable and not necessarily evidenced-based. Overall, for patients that are either anticoagulated or using antiplatelet drugs for secondary prophylaxis, there is a clear benefit to restarting these agents. However, there is limited data to guide when this should occur. For individuals at low risk of re-bleeding, current guidelines suggest single agent aspirin can be continued without interruption, assuming haemostatic control has been confirmed endoscopically. For those at higher bleeding risk, aspirin should be withheld, but reintroduced early (within 3 days of index endoscopy). However, randomised evidence is lacking, as are studies including more modern agents or combined anticoagulant/ antiplatelet regimens. As such, guidance statements are limited and management suggestions must be extrapolated from clinical trials, retrospective studies and data relating specifically to warfarin and aspirin. The intention of this review is to summarise what evidence is available and, where this is lacking, suggest pragmatic management options based on a risk-benefit assessment of thromboembolism and recurrent bleeding.
Topics: Anticoagulants; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 28272736
DOI: 10.1111/bjh.14599 -
American Journal of Hematology Dec 2011Clopidogrel is a widely used antiplatelet agent that irreversibly inhibits platelet P2Y12 ADP receptors after conversion to an active metabolite. There are a number of... (Review)
Review
Clopidogrel is a widely used antiplatelet agent that irreversibly inhibits platelet P2Y12 ADP receptors after conversion to an active metabolite. There are a number of laboratory tests capable of detecting clopidogrel-induced platelet inhibition and published literature correlates suboptimal clopidogrel response to adverse cardiovascular outcomes. Genetic polymorphisms are thought to affect conversion of the prodrug to the active metabolite, and the FDA has recently added a black-box warning to clopidogrel to highlight the effects of these polymorphisms on drug bioavailability and to inform prescribers about the availability of genetic testing. For these reasons, there is growing interest in the use of laboratory tests to monitor patients treated with clopidogrel. This article summarizes the currently available laboratory testing, including platelet function tests and genotyping for CYP2C19 variants.
Topics: Aryl Hydrocarbon Hydroxylases; Biological Availability; Biotransformation; Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Monitoring; Genotyping Techniques; Humans; Platelet Aggregation Inhibitors; Platelet Function Tests; Prodrugs; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticlopidine
PubMed: 21812020
DOI: 10.1002/ajh.22112 -
European Journal of Medicinal Chemistry Dec 2020Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of...
Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked.
Topics: Adult; Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Platelet Aggregation Inhibitors; Pyrimidines; Structure-Activity Relationship; Ticagrelor; Triazoles; Young Adult
PubMed: 32916314
DOI: 10.1016/j.ejmech.2020.112767 -
Vascular Health and Risk Management 2014Platelet activation with subsequent aggregation is a complex process leading to thrombus formation, which remains a key component for atherothrombotic manifestations, in... (Review)
Review
Platelet activation with subsequent aggregation is a complex process leading to thrombus formation, which remains a key component for atherothrombotic manifestations, in particular myocardial infarction. Therefore, antiplatelet therapies are pivotal for the treatment of these patients. Current oral antiplatelet therapies used for secondary prevention of ischemic recurrences include aspirin and adenosine diphosphate P2Y12 platelet-receptor antagonists. However, despite these therapies, patients who have experienced a myocardial infarction remain at risk for ischemic recurrences. Therefore, more aggressive secondary prevention measures have been an area of research, including identifying additional targets modulating platelet-activation and -aggregation processes. Among these, thrombin-mediated platelet activation via protease-activated receptors (PARs) has been subject to extensive clinical investigation. Several PAR-1 receptor antagonists have been developed. However, vorapaxar is the only one that has completed large-scale clinical investigation. The present manuscript will provide an overview on the role of thrombin-mediated signaling, the impact of PAR-1 blockade with vorapaxar on ischemic and bleeding outcomes, and the potential role for vorapaxar in clinical practice.
Topics: Animals; Blood Platelets; Hemorrhage; Humans; Lactones; Molecular Targeted Therapy; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyridines; Receptor, PAR-1; Risk Factors; Secondary Prevention; Signal Transduction; Treatment Outcome
PubMed: 24729713
DOI: 10.2147/VHRM.S36045