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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 -
Journal of Intensive Care Medicine Jan 2021Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care...
INTRODUCTION
Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage.
METHODS
We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution.
RESULTS
Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], < .001).
CONCLUSIONS
Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage.
Topics: Adult; Health Care Costs; Hospital Mortality; Hospitalization; Humans; Intensive Care Units; Intracranial Hemorrhages; Length of Stay; Platelet Aggregation Inhibitors; Retrospective Studies
PubMed: 31741418
DOI: 10.1177/0885066619885347 -
Endocrine, Metabolic & Immune Disorders... 2019The thienopyridine family includes ticlopidine, clopidogrel and prasugrel which are antiplatelet drugs largely used, mainly associated to aspirin, for treatment of acute... (Comparative Study)
Comparative Study Review
BACKGROUND AND OBJECTIVE
The thienopyridine family includes ticlopidine, clopidogrel and prasugrel which are antiplatelet drugs largely used, mainly associated to aspirin, for treatment of acute coronary syndromes and after percutaneous coronary interventions, to avoid thrombosis. In some patients, thienpyridines may cause hypersensitivity reactions which jeopardize the optimal therapeutic and preventive approach to vascular diseases. The management of thienopyridine hypersensitivity seems to be best done as an interdisciplinary collaboration between the allergist and cardiologist.
METHOD
The present study investigates the management of thienopyridines hypersensitivity on the basis of published case reports and studies, comparing the pro and contro of pharmacological treatments, different desensitization protocols to thienopyridines and substitution of antiplatelet agents eaches others, according to the point of view of cardiologist and allergist. For the cardiologist, the important issues are the necessity of continuing therapy, the desired duration of therapy based on the clinical indication of the individual patient and appropriateness of using one of the alternative P2Y12 inhibitors. For the allergist, the important issues are weighing the risk and benefits of the various therapeutic options: treating "through" desensitization, or switching to an alternative agent.
RESULTS AND CONCLUSION
All the data seem to suggest that only working together, a cardio-allergy team of specialists may evaluate and offer the best approach to clinical decision-making for the individual patient.
Topics: Allergists; Cardiologists; Clinical Decision-Making; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Patient Care Team; Platelet Aggregation Inhibitors; Thienopyridines
PubMed: 30215337
DOI: 10.2174/1871530318666180914121758 -
Scientific Reports Dec 2020Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane...
Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigate it. In cocultures of human platelets and coronary artery smooth muscle cells (CASMC), we found that platelets induced morphologic changes and enhanced the migration of CASMC. The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA and prevented the morphological and functional changes induced by platelets in CASMC. Platelet-derived TXA induced COX-2 and enhanced prostaglandin (PG)E biosynthesis in CASMC, a known mechanism promoting neointimal hyperplasia. COX-2 induction was prevented by different antiplatelet agents, i.e., Aspirin, the TP antagonist SQ29,548, or Revacept (a dimeric soluble GPVI-Fc fusion protein). The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation.
Topics: Adult; Animals; Blood Platelets; Cell Movement; Cell Proliferation; Coculture Techniques; Coronary Vessels; Cyclooxygenase 2; Glycoproteins; Humans; Hyperplasia; Immunoglobulin Fc Fragments; Male; Mice; Myocytes, Smooth Muscle; Neointima; Platelet Aggregation Inhibitors; Thromboxane A2; Urine; Young Adult
PubMed: 33293599
DOI: 10.1038/s41598-020-77934-x -
Interventional Cardiology Clinics Jan 2017Stroke prevention is the main priority in the management cascade of atrial fibrillation. Most patients require long-term oral anticoagulation (OAC) and may require... (Review)
Review
Stroke prevention is the main priority in the management cascade of atrial fibrillation. Most patients require long-term oral anticoagulation (OAC) and may require percutaneous coronary intervention. Prevention of recurrent cardiac ischemia and stent thrombosis necessitate dual antiplatelet therapy (DAPT) for up to 12 months. Triple antithrombotic therapy with OAC plus DAPT of shortest feasible duration is warranted, followed by dual antithrombotic therapy of OAC and antiplatelet agent, and OAC alone after 12 months. Because of elevated risk of hemorrhagic complications, new-generation drug-eluting stents, lower-intensity OAC, radial access, and routine use of gastric protection with proton pump inhibitors are recommended.
Topics: Atrial Fibrillation; Coronary Artery Disease; Drug-Eluting Stents; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombosis
PubMed: 27886825
DOI: 10.1016/j.iccl.2016.08.007 -
Blood Reviews Jan 2020Antiplatelet medications have long been the mainstay for secondary prevention in cardiovascular disorders. More recently, with the advent of coronary stents, there has... (Review)
Review
Antiplatelet medications have long been the mainstay for secondary prevention in cardiovascular disorders. More recently, with the advent of coronary stents, there has been an increased use of more potent antiplatelet agents to prevent stent occlusion. Since these drugs are antithrombotic, it is not unusual for them to be associated with serious bleeding, particularly intracranial and gastrointestinal haemorrhage. There are no robust guidelines on how to manage these clinical situations, although there have been some important studies published recently in this area. Similarly, there is very limited evidence on how to manage urgent surgery in patients receiving these medications. In this review, we provide updated guidance on the management of bleeding and surgery on antiplatelet drugs while stressing the need for further studies to provide evidence-based guidelines.
Topics: Hemorrhage; Humans; Platelet Aggregation Inhibitors
PubMed: 31648803
DOI: 10.1016/j.blre.2019.100619 -
International Journal of Stroke :... Apr 2015There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator... (Meta-Analysis)
Meta-Analysis Review
Prior antiplatelet agent use and outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: a meta-analysis of cohort studies and randomized controlled trials.
BACKGROUND
There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke.
AIM
We performed a systematic review with a final meta-analysis to evaluate the efficacy and safety of prior antiplatelet use before intravenous recombinant tissue plasminogen activator for acute ischemic stroke.
SUMMARY OF REVIEW
We searched PubMed and Embase databases from 1997 to 2014. Primary outcome was functional outcome at the end of follow-up; secondary outcomes were symptomatic intracranial hemorrhage and recanalization rate. The meta-analysis was performed with Review Manager 5.2 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). Eleven studies with a total of 19,453 patients were included. A total of 6517 (33.5%) patients who had received intravenous recombinant tissue plasminogen activator were taking antiplatelet agent before stroke onset. Pooled analysis demonstrated a clear trend that previous antiplatelet users had a reduced probability of good outcome, although it was not conventionally statistically significant (OR 0.86; 95% CI 0.73-1.01; P = 0.06). There was no difference in recanalization rate between two groups (OR 1.23; 95% CI 0.30-4.99; P = 0.77). The risk of symptomatic intracranial hemorrhage was significantly increased in the antiplatelet group (OR 1.65; 95% CI 1.44-1.90; P < 0.01).
CONCLUSIONS
In acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator therapy, prior antiplatelet agent use did not lead to a significant difference in functional outcome, although it significantly increased the risk of symptomatic intracranial hemorrhage. Recanalization rate was not different between two groups. In the subgroup analysis, prior clopidogrel mono therapy may not increase the risk of symptomatic intracranial hemorrhage, which will need further studies to confirm.
Topics: Cohort Studies; Databases, Bibliographic; Humans; Injections, Intravenous; Ischemia; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 25545076
DOI: 10.1111/ijs.12431 -
Pharmacotherapy Oct 2014Current percutaneous coronary intervention (PCI) guidelines recommend the use of a P2Y12 inhibitor with aspirin and an injectable anticoagulant. However, available oral... (Review)
Review
Current percutaneous coronary intervention (PCI) guidelines recommend the use of a P2Y12 inhibitor with aspirin and an injectable anticoagulant. However, available oral P2Y12 inhibitor therapy is limited by significant drug interactions, unclear oral absorption in selected clinical conditions, and delayed onset and offset of activity that may be cumbersome for patients requiring coronary artery bypass graft (CABG) surgery. Cangrelor, a novel intravenous P2Y12 inhibitor, offers potential advantages compared with currently available oral agents, particularly in regard to rapid onset and offset of platelet inhibition. The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) trials compared cangrelor versus an oral loading dose of clopidogrel, given before or after PCI, in patients with both stable and acute coronary syndromes. The results were conflicting, but some evidence demonstrated a lower rate of stent thrombosis compared with clopidogrel and lower rates of a composite cardiovascular end point, with comparable bleeding rates. The BRIDGE study assessed cangrelor as a replacement for oral P2Y12 inhibitors in patients awaiting CABG surgery and demonstrated that cangrelor maintained platelet inhibition during the preoperative period and enabled a rapid return to baseline platelet function upon cessation of the infusion. A new drug application was submitted to the Food and Drug Administration (FDA) for use during PCI to prevent thrombotic events and as bridging therapy for patients awaiting surgery who require therapy with P2Y12 inhibitors. In February 2014, the FDA's Cardiovascular and Renal Drugs Advisory Committee recommended against approval due to concerns over an appropriate risk-benefit ratio for use during PCI and a lack of evidence supporting the bridging indication. On April 30, 2014, the FDA issued a Complete Response letter for the PCI and bridging indications, denying approval and requesting further data. The future of this once promising novel intravenous antiplatelet agent is now in question.
Topics: Adenosine Monophosphate; Animals; Clinical Trials as Topic; Drug Approval; Forecasting; Humans; Infusions, Intravenous; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; United States
PubMed: 25123696
DOI: 10.1002/phar.1471 -
The Cochrane Database of Systematic... Oct 2017Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events.
OBJECTIVES
To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data.
MAIN RESULTS
We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ-5D-5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains.The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low-quality evidence). Investigators reported similar rates of clinically relevant non-major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate-quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ-5D-5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low-quality evidence) but not measured as health utility (MD 0.04, 95% CI -0.02 to 0.10 [on a scale from 0 to 1]).Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low-quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high-intensity warfarin treatment compared to the standard-intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low-quality evidence).In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60).
AUTHORS' CONCLUSIONS
There is not enough evidence for or against NOACs or for high-intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high-intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future.
Topics: Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Warfarin
PubMed: 28968483
DOI: 10.1002/14651858.CD012169.pub2 -
American Journal of Health-system... Sep 2019Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing... (Review)
Review
PURPOSE
Updates to the primary literature and clinical practice guidelines on use of antithrombotic combinations for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and stenting are reviewed.
SUMMARY
Up to 8% of patients undergoing PCI have AF and thus require both antiplatelet and anticoagulation therapies, which put them at increased risk for bleeding. Current literature suggests that using a single antiplatelet agent in combination with oral anticoagulation with a direct-acting oral anticoagulant (i.e., dual therapy) is effective and associated with less bleeding risk than triple therapy (dual antiplatelet therapy plus an oral anticoagulant) in patients with AF undergoing PCI with stent placement. The most recently studied dual therapy regimens consist of clopidogrel in combination with apixaban, rivaroxaban, or dabigatran. Guidelines recommend use of an oral anticoagulant plus clopidogrel and aspirin for a short period of time. In general, aspirin should be discontinued in most patients at discharge. In patients with a high risk of thrombosis, aspirin can be continued for up to 1 month. Dual therapy should be continued for 12 months, with oral anticoagulant monotherapy continued thereafter.
CONCLUSION
A review of current literature on antithrombotic therapy in patients with AF undergoing PCI and subsequent coronary artery stenting indicates that the favored regimen is dual therapy consisting of clopidogrel with rivaroxaban, apixaban, dabigatran, or a vitamin K antagonist. Aspirin may be used in the periprocedural period but should be discontinued thereafter to reduce the risk of bleeding. Decisions regarding specific agents and duration of treatment should be based on thrombotic risk, bleeding risk, and patient preference.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Loss, Surgical; Clinical Decision-Making; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Humans; Patient Preference; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Practice Guidelines as Topic; Risk Assessment; Stents; Thrombosis; Time Factors
PubMed: 31505555
DOI: 10.1093/ajhp/zxz152