RESUMEN
The recent study by Kaiwen Wang et al., titled "Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage," explores the association between postoperative intracranial bleeding (PIB) and various risk factors, including smoking, pre-hemorrhagic antiplatelet therapy, and dyslipidemia. While the study highlights that smoker, particularly women, are at increased risk for subarachnoid hemorrhage and acknowledges the risks of pre-hemorrhagic antiplatelet use, it overlooks the potential risk of PIB associated with early postoperative aspirin administration. This critique underscores the need to approach the study's findings with caution, given the broader context of aspirin's risk profile. Specifically, aspirin has been associated with a 37% higher relative risk of any intracranial hemorrhage, as indicated by other randomized trials. Additionally, the study's implications regarding the benefits of aspirin in stroke prevention must be critically evaluated, as the increased risk of intracranial bleeding may outweigh the potential benefits. This abstract emphasizes the importance of careful consideration of aspirin's adverse effects in the context of postoperative care.
Asunto(s)
Aspirina , Hemorragia Cerebral , Inhibidores de Agregación Plaquetaria , Humanos , Aspirina/efectos adversos , Aspirina/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Factores de Riesgo , Hemorragias Intracraneales , Femenino , Complicaciones Posoperatorias , Hemorragia Posoperatoria , MasculinoRESUMEN
Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.
Asunto(s)
Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificaciónRESUMEN
Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
Asunto(s)
Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Método Doble Ciego , Ataque Isquémico Transitorio/tratamiento farmacológico , China/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Understanding the cost-effectiveness of aspirin-clopidogrel combination therapy is crucial in determining its influence on coagulation parameters, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT). The aim of this study was to assess the cost-effectiveness and clinical impact of using the aspirin-clopidogrel combination compared to aspirin alone in managing ischemic stroke. Employing an observational research design, inpatient ischemic stroke cases receiving the aspirin-clopidogrel combination were compared to those treated with aspirin alone. Focusing on the hospital's perspective on costs, the research specifically analyzed medical expenses without discounting costs or effects. The analysis involved comparing the direct medical costs and coagulation parameters between the two treatment groups. Our data revealed that the aspirin-clopidogrel combination demonstrated superior cost-effectiveness over aspirin alone, indicated by the incremental cost-effectiveness ratio (ICER) values for PT (IDR -246,930/second) and APTT (IDR -119,270/second). This indicated that the combination therapy was associated with lower costs while yielding better clinical parameter values. The ICER analysis placed the aspirin-clopidogrel combination in the southeast quadrant, marking its dominance over aspirin monotherapy by demonstrating higher effectiveness at lower costs. These results suggest that combination therapy might be a favorable alternative for managing ischemic stroke, presenting a viable option for consideration in clinical practice. The findings underscore the potential economic and clinical advantages of employing the aspirin-clopidogrel combination in routine stroke management protocols.
Asunto(s)
Aspirina , Clopidogrel , Análisis Costo-Beneficio , Quimioterapia Combinada , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Aspirina/uso terapéutico , Aspirina/economía , Aspirina/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/economíaAsunto(s)
Aspirina , Enfermedad de Chagas , Lipoxinas , Trypanosoma cruzi , Aspirina/farmacología , Aspirina/uso terapéutico , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/genética , Animales , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/prevención & control , Lipoxinas/metabolismo , Ratones , Modelos Animales de Enfermedad , HumanosRESUMEN
Investigate the effect of Alteplase and Aspirin on the functional outcomes of patients with acute ischemic stroke with mild non-disabling neurological deficit. In this single-center, randomized controlled study, we selected 60 patients with acute ischemic stroke with mild non-disabling neurological deficit admitted to our hospital from January 2021 to January 2022, and randomly divided them into the study group (nâ =â 30) and the control group (nâ =â 30), the control group was given the Aspirin treatment, the study group was given the Alteplase treatment, and the changes in neurological recovery, daily living ability, exercise ability, balance ability, cognitive function, and short-term prognosis outcomes were observed in these 2 groups. The factors influencing the short-term outcome of Alteplase therapy in patients with acute ischemic stroke were analyzed. The National Institutes of Health Neurological Deficit Score (NIHSS) scores at T1 and T2 of the study group were lower than those in the control group, but the scores of Barthel indicators (BI), Fugl-Meyer Motor Assessment Scale (FMA), Berg Balance Scale (BBS) and Montreal Cognitive Assessment Scale (MoCA) of the study group were higher than those in the control group, and the difference was statistically significant (Pâ <â .05). The short-term prognostic outcomes of these 2 groups were not significantly different (Pâ >â .05). The effect of the use of Alteplase or Aspirin on short-term functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit is not much different.
Asunto(s)
Aspirina , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Activador de Tejido Plasminógeno , Humanos , Aspirina/uso terapéutico , Femenino , Masculino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Fibrinolíticos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento , Recuperación de la Función/efectos de los fármacos , Actividades Cotidianas , PronósticoRESUMEN
BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Femenino , Masculino , Anciano , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Terapia Antiplaquetaria Doble/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/diagnóstico , Aterosclerosis/complicaciones , Índice de Severidad de la Enfermedad , Quimioterapia CombinadaRESUMEN
BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.
Asunto(s)
Aspirina , Clopidogrel , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Insuficiencia Renal Crónica , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Anciano , Hemorragia/inducido químicamente , Resultado del Tratamiento , Tasa de Filtración Glomerular , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Stents , Factores de TiempoRESUMEN
BACKGROUND: The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS: Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS: Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS: The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.
Asunto(s)
Aspirina , Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Células Madre Mesenquimatosas , Estrés Oxidativo , Ratas Wistar , Animales , Masculino , Aspirina/farmacología , Ratas , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Cognición/efectos de los fármacos , Antioxidantes/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.
Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Femenino , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Factores de Tiempo , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
Introduction: Endometriosis is delineated as a benign yet steroid-dependent disorder characterized by the ectopic presence of endometrial glandular and stromal cells outside the uterine cavity, affecting estimated 10%-15% of women of reproductive age, 20%-50% of all women with infertility and costing a great economic burden per-patient. Endometriosis exerts pervasive influence on multiple facets of female reproductive physiology. Given its characterization as a chronic inflammatory disorder, escalated levels of pro-inflammatory cytokines were unequivocally recognized as well-established characteristics of endometriosis, which might attribute to mechanisms like retrograde menstruation, progesterone receptor resistance, and immune dysregulation. Therapeutic utilization of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, analgesic agent for reducing pain, inflammation, and fever, could be holding promise in augmenting reproductive outcomes of endometriosis women. Therefore, the objective of this comprehensive review is to elucidate the intricate interplay between endometriosis and aspirin, both within the context of infertility and beyond. We meticulously explore potential pharmacological agents targeting endometriosis, which may concurrently optimize the efficacy of reproductive interventions, while also delving into the underlying mechanistic pathways linking endometriosis with inflammatory processes. Methods: We conducted a comprehensive search in the data available in PubMed and the Web of Science using the terms 'endometriosis' and 'aspirin'. Then analyzed the identified articles based on established inclusion and exclusion criteria independently by three reviewers. Results: The survey of the chosen terms revealed 72 articles, only 10 of which were considered for review. Discussion: Based on the research available currently, it is not substantial enough to address the conclusion that aspirin shall be an effective therapeutic choice for endometriosis, further studies are needed to elucidate the efficacy, safety profile, and optimal dosing regimens of aspirin in the context of endometriosis treatment.
Asunto(s)
Antiinflamatorios no Esteroideos , Aspirina , Endometriosis , Endometriosis/tratamiento farmacológico , Humanos , Femenino , Aspirina/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Infertilidad Femenina/tratamiento farmacológicoRESUMEN
Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.
Asunto(s)
Glucuronidasa , Pancreatitis , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología , Ratones , Glucuronidasa/metabolismo , Glucuronidasa/antagonistas & inhibidores , Trehalosa/farmacología , Trehalosa/uso terapéutico , Ceruletida , Aspirina/farmacología , Aspirina/uso terapéutico , Modelos Animales de Enfermedad , Enfermedad Aguda , Autofagia/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/patología , Páncreas/enzimología , Masculino , Ratones Transgénicos , Lipasa/metabolismo , Lipasa/antagonistas & inhibidores , Amilasas/sangre , Ratones Endogámicos C57BL , SaponinasRESUMEN
Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.
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Aspirina , Inhibidores del Factor Xa , Accidente Cerebrovascular Isquémico , Neoplasias , Pirazoles , Piridonas , Humanos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Masculino , Femenino , Aspirina/uso terapéutico , Aspirina/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Anciano , Persona de Mediana Edad , Método Doble Ciego , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/epidemiología , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Hemorragia/inducido químicamenteRESUMEN
Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1-3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1-3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0-2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1-2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.
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Anticuerpos Monoclonales Humanizados , Aspirina , Bevacizumab , Carcinoma Hepatocelular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Insulina , Neoplasias Hepáticas , Metformina , Compuestos de Fenilurea , Quinolinas , Humanos , Metformina/uso terapéutico , Metformina/administración & dosificación , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Anciano , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Pronóstico , Insulina/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.
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Análisis Costo-Beneficio , Aneurisma Intracraneal , Inhibidores de Agregación Plaquetaria , Pruebas de Función Plaquetaria , Humanos , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/economía , Clopidogrel/uso terapéutico , Clopidogrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/economía , Aspirina/uso terapéutico , Aspirina/economía , Ticagrelor/uso terapéutico , Terapia Antiplaquetaria Doble/métodosRESUMEN
OBJECTIVE: Forgerini et al. investigated the role of seven genetic variants in the risk of upper gastrointestinal bleeding as an adverse drug reaction. In 289 participants (50 cases and 189 controls), the presence of seven variants in the IL-1ß, IL-1RN, and TNF-α genes was not associated with susceptibility to acetylsalicylic acid-induced upper gastrointestinal bleeding. The use of acetylsalicylic acid, even in low doses, may be associated with the onset of upper gastrointestinal bleeding as an idiosyncratic response. Considering the role of the genetic background in inter-individual responses to pharmacotherapy, we aimed to investigate the role of seven variants in the TNF-α, IL-ß, and IL-1RN genes in association with the risk of upper gastrointestinal bleeding in users of low-dose acetylsalicylic acid for the prevention of cardiovascular events. METHODS: A case-control study was conducted in a Brazilian hospital complex. The Case Group comprised patients diagnosed with upper gastrointestinal bleeding who were administered a low dose of acetylsalicylic acid (n=50). Two Control Groups were recruited: 1) low-dose acetylsalicylic acid users without gastrointestinal complaints and under the supervision of a cardiologist (n=50) and 2) healthy controls (n=189). Sociodemographic, clinical, pharmacotherapeutic, and lifestyle data were recorded through face-to-face interviews. Genomic DNA from all participants was genotyped for rs16944 and rs1143634 (IL-ß gene), rs4251961 (IL-1RN gene), and rs1799964, rs1799724, rs361525, and rs1800629 (TNF-α gene). RESULTS: No significant difference was noted in the genotypic frequencies of TNF-α, IL-ß, and IL-1RN variants between the Case and Control Groups of low-dose acetylsalicylic acid users (p>0.05). The frequency of rs1800629 genotypes (TNF-α gene) differed significantly between the Case Group and healthy controls (p=0.003). None of the evaluated variants were associated with a risk of upper gastrointestinal bleeding. CONCLUSION: This study aimed to explore pharmacogenomics biomarkers in low-dose acetylsalicylic acid users. Our data suggest that the presence of IL-1ß, IL-1RN, and TNF-α variants was not associated with an increased risk of upper gastrointestinal bleeding.
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Aspirina , Hemorragia Gastrointestinal , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1beta , Factor de Necrosis Tumoral alfa , Humanos , Masculino , Estudios de Casos y Controles , Femenino , Aspirina/efectos adversos , Factor de Necrosis Tumoral alfa/genética , Interleucina-1beta/genética , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/genética , Persona de Mediana Edad , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Anciano , Factores de Riesgo , Genotipo , Predisposición Genética a la Enfermedad/genética , Adulto , Polimorfismo de Nucleótido SimpleRESUMEN
Cranial operations are associated with a high risk of postoperative intracranial hemorrhage (pICH) and venous thromboembolic events, along with increased mortality and morbidity. With the use of acetylsalicylic acid (ASA) for prophylaxis becoming more prevalent, the risk of bleeding when ASA is administered preoperatively is unknown, as are the effects of discontinuation upon the occurrence of thromboembolic events, especially in societies with aging demographics. To address these questions, a retrospective analysis was performed using medical records and radiological images of 1862 patients subjected to brain tumor surgery over a decade in our department. The risk of pICH was compared in patients with metastases receiving ASA treatment versus patients not receiving ASA treatment. The occurrence of venous thromboembolic events after surgery was also evaluated. The study group consisted of 365 patients with different types of brain metastases. In total, 20 patients suffered pICH and 7 of these were associated with clinical neurological deterioration postoperatively. Of the 58 patients who took ASA preoperatively, 2 patients experienced pICH, compared with 5 patients in the non-ASA impact group (p = 0.120). Patients who took ASA were not at significantly higher risk of pICH and therefore a worse outcome compared to the group without ASA. Therefore, these data suggest that in patients at high cardiovascular risk, ASA can be safely continued during elective brain tumor surgery.
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Aspirina , Neoplasias Encefálicas , Hemorragias Intracraneales , Tromboembolia Venosa , Humanos , Aspirina/uso terapéutico , Aspirina/efectos adversos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Masculino , Femenino , Tromboembolia Venosa/etiología , Persona de Mediana Edad , Anciano , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/etiología , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Complicaciones PosoperatoriasRESUMEN
Antiphospholipid syndrome (APS) is the most frequent acquired thrombophilia of autoimmune basis. Pregnancy complications of APS may include recurrent miscarriage, and placental dysfunction presenting as fetal death, prematurity, intrauterine growth restriction and preeclampsia. For the management of obstetric APS, a coordinated medical-obstetric management is essential, and this should start for a preconceptional visit in order to estimate the individual risk for complications, adjust therapies and establish the indications for preconceptional and first-trimester therapy. The basis of APS therapy during pregnancy is low-dose aspirin, combined in certain clinical scenarios with low-molecular weight heparin. Induction of delivery should not be routinely indicated in the absence of maternal and/or fetal complications. Postpartum management should be warranted.
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Síndrome Antifosfolípido , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Humanos , Embarazo , Femenino , Aspirina/uso terapéutico , Complicaciones del Embarazo/terapia , Complicaciones del Embarazo/diagnóstico , Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapiaRESUMEN
Influenza infection is associated with a risk of thrombosis. Whether factors associated with reduced thrombosis might also be associated with reduced risk in patients with severe influenza is unknown. To investigate risk factors associated with thrombosis in patients with severe influenza. We used a cohort data set to identify adults diagnosed with severe influenza. Univariable and multivariable logistic regression models explored potential risk factors for thrombosis events in patients with severe influenza. Cox regression analysis was used to examine the risk factors for mortality in patients with severe influenza. A total of 854 patients with severe influenza were included in the analysis. The incidence of VTE was 9.37% (80/854). Multivariable regression analysis showed that previous aspirin medication (OR: 0.37; 95%CI: 0.14-0.84; P = .029) could reduce the risk factor of thrombosis in patients with severe influenza. Compared with patients in the non-thrombosis group, patients in the thrombosis group required more mechanical ventilation (P < .001), tracheostomy (P < .001), ECMO (P = .046), and high-frequency ventilation (P = .004). The incidence of co-infection was higher in the thrombosis group compared to the non-thrombosis group (P = .025). Univariable Cox regression analysis showed that previous aspirin medication (HR 0.52, 95%CI: 0.33-0.82, P = .005) and previous statin medication (HR 0.54, 95%CI: 0.34-0.87, P = .011) were risk factors for 60-day mortality in patients with severe influenza. Patients with severe influenza are at high risk for thrombosis. The effect of aspirin on thrombosis in patients with severe influenza needs further investigation.
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Enfermedad Crítica , Gripe Humana , Trombosis , Humanos , Gripe Humana/complicaciones , Gripe Humana/epidemiología , Factores de Riesgo , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Trombosis/etiología , Trombosis/epidemiología , Anciano , Adulto , Aspirina/uso terapéuticoRESUMEN
Impedance aggregometry is an alternative to light transmission aggregometry that allows analysis of platelet function in whole blood samples. We hypothesized (1) impedance aggregometry would produce repeatable results, (2) inhibition of cyclooxygenase with aspirin would attenuate aggregation responses to collagen and abolish the aggregation response to arachidonic acid (AA), and (3) thromboxane receptor antagonism (terutroban) would attenuate the aggregation response to AA. Venous blood was obtained from 11 participants three times separated by at least 2 weeks. One sample followed 7-day-aspirin intervention (81 mg once daily; ASA), the others no intervention (control). Aggregation was induced using 1 µg/mL collagen ([col 1]), 5 µg/mL collagen ([col 5]), and 50 mM AA via impedance aggregometry to determine total aggregation (AUC) analyzed for intra-test repeatability, inter-test repeatability, intervention (ASA or control), and incubation (saline or terutroban). [col 1] showed high intra-test (p ≤ 0.03 visit 1 and 2) and inter-test repeatability (p < 0.01). [col 5] and AA showed intra- ([col 5] p < 0.01 visit 1 and 2; AA p < 0.001 visit 1 and 2) but not inter-test repeatability ([col 5] p = 0.48; AA p = 0.06). ASA attenuated AUC responses to [col 1] (p < 0.01), [col 5] (p = 0.03), and AA (p < 0.01). Terutroban attenuated AUC in response to AA (p < 0.01). [col 1] shows sufficient repeatability for longitudinal investigations of platelet function. [col 5] and AA may be used to investigate mechanisms of platelet function and metabolism at a single time point.