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1.
Ren Fail ; 46(2): 2380754, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39039846

RESUMEN

BACKGROUND: Hemodialysis (HD) patients with peripheral arterial disease (PAD) are at heightened risk of adverse vascular events, and aspirin positively affects those outcomes. We aimed to investigate the association between different patterns of aspirin use and clinical vascular events in chronic HD patients with PAD. METHODS: This retrospective nationwide cohort study enrolled 758 chronic HD patients who had been diagnosed with PAD between January 1, 2008, and December 31, 2012, and followed up until the end of 2020. Patients were divided into three groups according to medication possession ratio (MPR) and continued use of aspirin (i.e., low MPR, high MPR but discontinuous prescription, and high MPR and continuous prescription). Percutaneous transluminal angioplasty (PTA), surgical bypass, lower leg amputation, cardiovascular events, cerebrovascular events, and all-cause mortality were evaluated. RESULTS: High MPR and continuous aspirin use had the lowest incidence of all-cause mortality and cardiovascular events compared with the two other groups, and it was significantly associated with low risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality (aHR: 0.58 [0.41-0.83], 0.49 [0.25-0.95], 0.57 [0.40-0.81], and 0.70 [0.55-0.88], respectively). Kaplan-Meier analysis revealed that event-free rates of PTA, cardiovascular events, and all-cause mortality of patients with high MPR and continuous aspirin treatment were the highest among the three groups (p < 0.05). CONCLUSION: Among HD patients with PAD, high MPR and continuous aspirin use significantly reduced the risk of PTA, surgical bypass, cardiovascular events, and all-cause mortality and improved the event-free rates of PTA, cardiovascular events, and all-cause mortality during long-term follow-up.


Asunto(s)
Aspirina , Enfermedad Arterial Periférica , Inhibidores de Agregación Plaquetaria , Diálisis Renal , Humanos , Aspirina/uso terapéutico , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad
2.
Syst Rev ; 13(1): 173, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978122

RESUMEN

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. Presenting features include new-onset headaches, constitutional symptoms, jaw claudication, polymyalgia rheumatica, and visual symptoms. Arterial inflammation with subsequent stenosis and occlusion may cause tissue ischemia, leading to blindness, strokes, and myocardial infarction. Oral antiplatelet therapy has been hypothesized to reduce GCA-related ischemic events. However, previous studies have demonstrated conflicting results regarding the efficacy of antiplatelet agents in GCA. The objective of this systematic review is to assess the safety and efficacy of antiplatelet therapy for the prevention of these events in adults with giant cell arteritis. METHODS: In this systematic review, we will include randomized controlled trials (RTCs), quasi-randomized trials, non-randomized intervention studies, cohort studies, and case-control studies on patients with new-onset or relapsing GCA. The intervention of interest will be pre-existing use or initiation of an oral antiplatelet medication (aspirin, clopidogrel, prasugrel, or ticagrelor) at GCA onset or relapse. The comparator of interest will be the absence of antiplatelet therapy. Endpoints will be evaluated after 6 and 12 months of follow-up. The primary outcome will be GCA-related ischemic events, including permanent blindness, stroke, myocardial infarction, and ischemic event-related deaths. Adverse events such as major bleeding and death caused by a bleeding event will be assessed. DISCUSSION: GCA-related ischemic events are catastrophic, sudden, often irreversible, and lead to significant morbidity. Antiplatelet agents are affordable, accessible, and could be effective for the prevention of these events. Nevertheless, the potential benefits of platelet aggregation inhibition must be weighed against their associated risk of bleeding. Assessing the efficacy and safety of antiplatelet therapy in GCA is therefore clinically important. SYSTEMATIC REVIEW REGISTRATION: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42023441574.


Asunto(s)
Arteritis de Células Gigantes , Inhibidores de Agregación Plaquetaria , Revisiones Sistemáticas como Asunto , Humanos , Arteritis de Células Gigantes/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Metaanálisis como Asunto , Isquemia/prevención & control , Infarto del Miocardio/prevención & control
3.
EuroIntervention ; 20(14): e898-e904, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007830

RESUMEN

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.


Asunto(s)
Anticoagulantes , Fibrilación Atrial , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Administración Oral , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia/inducido químicamente , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Masculino , Femenino , Anciano , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Resultado del Tratamiento , Persona de Mediana Edad
4.
PLoS One ; 19(7): e0306445, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38991024

RESUMEN

Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population.


Asunto(s)
Plaquetas , Clopidogrel , Secuenciación de Nucleótidos de Alto Rendimiento , Inhibidores de Agregación Plaquetaria , Polimorfismo de Nucleótido Simple , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/farmacología , Masculino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Persona de Mediana Edad , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Anciano , Herencia Multifactorial/genética , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Ticlopidina/farmacología
5.
S D Med ; 77(5): 213-219, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39012774

RESUMEN

Heart failure (HF) is a common disorder associated with significant morbidity and mortality. It can increase the risk of thromboembolic events, which subsequently lead to increased risk of stroke, ischemic heart disease, thromboembolism, and death. Antithrombotic therapy has been investigated as a potential management strategy for HF patients in sinus rhythm, but its efficacy remains uncertain. Current guidelines do not recommend the routine use of antithrombotics in patients with HF in sinus rhythm without any other indication for their use. Several randomized controlled trials have investigated the efficacy of antithrombotics in HF patients in sinus rhythm. This article provides a concise review of the existing literature to assess the evidence supporting the use of antithrombotics in HF patients in sinus rhythm. The use of warfarin or other anticoagulants has demonstrated a lower risk of stroke but an increased risk of bleeding. The studies demonstrate that anticoagulant therapy in HF patients in sinus rhythm does not provide significant benefits in terms of overall ischemic events or death.


Asunto(s)
Fibrinolíticos , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Fibrinolíticos/uso terapéutico , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Warfarina/uso terapéutico , Warfarina/efectos adversos , Tromboembolia/prevención & control , Accidente Cerebrovascular/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico
6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(7): 1062-1068, 2024 Jul 06.
Artículo en Chino | MEDLINE | ID: mdl-39034792

RESUMEN

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group (n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group (n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group (χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595,P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.


Asunto(s)
Aspirina , Infarto Cerebral , Inhibidores de Agregación Plaquetaria , Recurrencia , Humanos , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Infarto Cerebral/prevención & control , Persona de Mediana Edad , Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Método Simple Ciego , Prevención Secundaria/métodos , Accidente Cerebrovascular/prevención & control
7.
Artículo en Inglés | MEDLINE | ID: mdl-39008642

RESUMEN

Objective: Acetylsalicylic acid (ASA) is the most widely used antiplatelet agent in treating ischemic strokes. ASA resistance varies between the populations, from 5% to 60%. We aimed to determine the prevalence of ASA resistance in our population, its association with demographic characteristics, risk factors, and the occurrence of recurrent ischemic stroke (IS). (IST). Methods: One hundred consecutive patients with primary or recurrent IS were prospectively included. Strokes were diagnosed with computed tomography (CT) or magnetic resonance imaging (MRI). In all patients a detailed history of cardiovascular risk factors and fasting blood analyzes (blood count, glycemia, HbA1c, degradation products, lipid profile) were taken, and the ASA resistance was examined with the Innovance PFA 200 system. The ASA resistance was examined after a minimum of 1 month of regular use of ASA 100 mg per day. Results: The prevalence of ASA resistance was 32%. ASA-resistant patients were statistically significantly older (69.9±7.5 vs, 61±1 y., p<0.05), and of male gender (75 vs, 45.6%, p<0.05). Previous cardiovascular diseases were statistically significantly more common in the ASA-resistant patients compared to the ASA-sensitive patients (46.8 vs 26.5%, p<0.05). The presence of recurrent stroke in the ASA-resistant versus ASA-sensitive patients was statistically significant (75% vs. 22.05%, p<0.0001). There was no statistically significant difference in the investigated laboratory parameters and the risk factors between the ASA-resistant and the ASA-sensitive patients. Conclusion. The prevalence of ASA resistance in our population is high. According to our results, ASA resistance testing should be done in the older male individuals with a previous burden of cardiovascular diseases.


Asunto(s)
Aspirina , Resistencia a Medicamentos , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Recurrencia , Humanos , Masculino , Aspirina/uso terapéutico , Femenino , Anciano , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Accidente Cerebrovascular Isquémico/epidemiología , Estudios Prospectivos , Factores de Riesgo , Prevalencia , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X
10.
Circulation ; 150(4): 317-335, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39038086

RESUMEN

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.


Asunto(s)
Síndrome Coronario Agudo , Terapia Antiplaquetaria Doble , Inhibidores de Agregación Plaquetaria , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia/inducido químicamente , Intervención Coronaria Percutánea , Factores de Tiempo , Resultado del Tratamiento , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Esquema de Medicación
11.
Expert Rev Cardiovasc Ther ; 22(7): 339-345, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949642

RESUMEN

BACKGROUND: Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. RESEARCH DESIGN AND METHODS: A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. RESULTS: Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). CONCLUSIONS: TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.


Asunto(s)
Anticoagulantes , Aspirina , Fibrilación Atrial , Clopidogrel , Quimioterapia Combinada , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Hemorragia/inducido químicamente , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Anciano de 80 o más Años , Ticagrelor/administración & dosificación , Ticagrelor/uso terapéutico , Ticagrelor/efectos adversos
12.
CNS Neurosci Ther ; 30(7): e14868, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39014552

RESUMEN

BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.


Asunto(s)
Presión Sanguínea , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Accidente Cerebrovascular , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Anciano , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Anciano de 80 o más Años , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológico
14.
Lupus Sci Med ; 11(2)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977356

RESUMEN

OBJECTIVES: Hydroxychloroquine (HCQ) has been shown to reduce thrombotic events in patients with SLE. However, the antiplatelet effects of HCQ are only supported by the platelet aggregation assay, which is a non-physiological test. The total thrombus-formation analysis system (T-TAS) is a microchip-based flow chamber system that mimics physiological conditions and allows for the quantitative analysis of thrombogenicity. The present study investigated the antiplatelet effects of HCQ using T-TAS. METHODS: This was a single-centre cross-sectional study on 57 patients with SLE. We measured the area under the pressure curve for 10 min (PL-AUC10) and the time to 10 kPa (T10) in patients with SLE using T-TAS and examined their relationships with the use of HCQ. PL-AUC10 and platelet aggregation were also measured at several HCQ concentrations using blood samples from healthy donors. RESULTS: PL-AUC10 was significantly lower in the HCQ/real body weight (RBW) ≥5 mg/kg group than in the <5 mg/kg group, while T10 was similar, indicating that HCQ inhibited overall thrombus formation rather than the initiation of thrombus formation. The antiplatelet effects of HCQ were initially detected at HCQ/RBW of approximately 4 mg/kg and reached a plateau at around 5.5 mg/kg. The administration of HCQ/RBW >4.6 mg/kg clearly exerted antiplatelet effects. Additionally, HCQ inhibited thrombus formation in T-TAS and the platelet aggregation response to epinephrine in a dose-dependent manner. CONCLUSIONS: We demonstrated the antiplatelet effects of HCQ under conditions simulating the physiological environment by using T-TAS and identified the range of doses at which HCQ exerted antiplatelet effects.


Asunto(s)
Hidroxicloroquina , Lupus Eritematoso Sistémico , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria , Trombosis , Humanos , Hidroxicloroquina/uso terapéutico , Femenino , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/sangre , Masculino , Agregación Plaquetaria/efectos de los fármacos , Adulto , Estudios Transversales , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/prevención & control , Trombosis/etiología , Trombosis/tratamiento farmacológico , Persona de Mediana Edad , Adulto Joven , Pruebas de Función Plaquetaria/métodos , Antirreumáticos/uso terapéutico
15.
Eur J Cardiothorac Surg ; 66(1)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38970368

RESUMEN

OBJECTIVES: To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field. METHODS: We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA. RESULTS: Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001). CONCLUSIONS: Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.


Asunto(s)
Puente de Arteria Coronaria , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Puente de Arteria Coronaria/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Hemorragia Posoperatoria/epidemiología , Privación de Tratamiento/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Enfermedad de la Arteria Coronaria/cirugía
16.
Sci Rep ; 14(1): 15003, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951544

RESUMEN

While the efficacy of GpIIb-IIIa-inhibitors during primary PCI (pPCI) for ST-elevated myocardial infarction (STEMI) has previously been demonstrated, its ongoing role and safety in combination with newer P2Y12-inhibitors is unclear. We therefore sought to compare outcomes between two centers with divergent approaches to the use of GpIIbIIIa antagonists in pPCI. We performed a retrospective chart review of all-comer STEMI patients treated with pPCI at two high-volume Montreal academic tertiary care centers. One center tended to use GpIIb-IIIa-inhibitors up-front in a large proportion of patients (liberal strategy) and the other preferring a bail-out approach (conservative strategy). Baseline patient characteristics and procedural data were compared between the two groups. The main efficacy outcome was rate of no-reflow/slow-reflow and the main safety outcome was BARC ≥ 2 bleeding events. A total of 459 patients were included, of whom 167 (36.5%) were exposed to a GpIIb-IIIa-antagonist. There was a significant overall difference in use of GpIIb-IIIa-antagonist between the two centers (60.5% vs. 16.1%, p < 0.01). Rate of no-reflow/slow-reflow was similar between groups (2.6% vs. 1.4%, p = 0.22). In-hospital rates of unplanned revascularization, stroke and death were also not different between groups. Use of a liberal GpIIb--IIIa-antagonist strategy was however associated with a higher risk of bleeding (OR 3.16, 95% CI 1.57-6.37, p < 0.01), which persisted after adjustment for covariables (adjusted OR 2.85, 95% CI 1.40-5.81, p < 0.01). In this contemporary retrospective cohort, a conservative, bail-out only GpIIb--IIIa-antagonist strategy was associated with a lower incidence of clinically relevant bleeding without any signal for an increase in no-reflow/slow-reflow or ischemic clinical events.


Asunto(s)
Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Femenino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Estudios Retrospectivos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del Tratamiento , Hemorragia
17.
J Cardiothorac Surg ; 19(1): 422, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965617

RESUMEN

OBJECTIVE: Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery. METHODS: This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias. RESULTS: A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events. CONCLUSIONS: Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.


Asunto(s)
Puente de Arteria Coronaria , Fibrinolíticos , Inhibidores de Agregación Plaquetaria , Estudios Retrospectivos , Estudios de Cohortes , Puente de Arteria Coronaria/efectos adversos , Periodo Posoperatorio , Fibrinolíticos/uso terapéutico , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quimioterapia Combinada , Hemorragia/prevención & control , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano
18.
BMC Neurol ; 24(1): 231, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961337

RESUMEN

BACKGROUND: Trans-radial (TRA) access has become increasingly prevalent in neurointervention. Nonetheless, mediastinal hematoma after TRA is an infrequent yet grave complication associated with a notably elevated mortality rate. While our review found no reported mediastinal hematoma cases managed conservatively within neuro-interventional literature, similar complications are documented in cardiac and vascular interventional radiology, indicating its potential occurrence across disciplines. CASE PRESENTATION: Carotid computed tomography angiography (CTA) showed calcified plaques with stenosis (Left: Severe, Right: Moderate) in the bilateral internal carotid arteries (ICAs) of an 81-year-old male presented with paroxysmal weakness in the right upper limb. Dual antiplatelet therapy with aspirin and clopidogrel was administered. On day 7, DSA of the bilateral ICAs was performed via TRA. Post-DSA, the patient experienced transient loss of consciousness, chest tightness, and other symptoms without ECG or MRI abnormalities. Hemoglobin level decreased from 110 g/L to 92 g/L. Iodinated contrast-induced laryngeal edema was suspected, and the patient was treated with intravenous methylprednisolone. Neck CT indicated a possible mediastinal hemorrhage, which chest CTA confirmed. The patient's treatment plan involved discontinuing antiplatelet medication as a precautionary measure against the potential occurrence of an ischemic stroke instead of the utilization of a covered stent graft and surgical intervention. Serial CTs revealed hematoma absorption. Discharge CT showed a reduced hematoma volume of 35 × 45 mm. CONCLUSIONS: This case underscores the need for timely identification and precise manipulation of guidewires and guide-catheters through trans-radial access. The critical components of successful neuro-interventional techniques include timely examination, rapid identification, proper therapy, and diligent monitoring.


Asunto(s)
Hematoma , Humanos , Masculino , Anciano de 80 o más Años , Hematoma/diagnóstico por imagen , Hematoma/etiología , Angiografía Cerebral/efectos adversos , Angiografía Cerebral/métodos , Enfermedades del Mediastino/diagnóstico por imagen , Enfermedades del Mediastino/etiología , Arteria Radial/diagnóstico por imagen , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estenosis Carotídea/diagnóstico por imagen
19.
Int J Mol Sci ; 25(14)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39062819

RESUMEN

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs.


Asunto(s)
Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Humanos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Receptores Purinérgicos P2Y12/metabolismo , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Transducción de Señal/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Animales
20.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39063087

RESUMEN

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.


Asunto(s)
Enfermedades Cardiovasculares , Fibrinolíticos , Hemofilia A , Hemorragia , Humanos , Hemofilia A/tratamiento farmacológico , Hemofilia A/complicaciones , Hemorragia/inducido químicamente , Hemorragia/etiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores de Riesgo
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