RESUMEN
Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure.
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Apéndice Atrial , Fibrilación Atrial , Fibrinolíticos , Humanos , Apéndice Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Cateterismo Cardíaco/métodos , Dispositivo Oclusor Septal , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Accidente Cerebrovascular Isquémico/prevención & control , Trombosis/prevención & control , Trombosis/etiologíaRESUMEN
The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.
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Fibrinolíticos , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Enfermedad Crónica , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Terapia Antiplaquetaria Doble/métodosRESUMEN
BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).
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Eptifibatida , Hemorragias Intracraneales , Accidente Cerebrovascular Isquémico , Péptidos , Ácidos Pipecólicos , Sulfonamidas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arginina/administración & dosificación , Arginina/efectos adversos , Arginina/análogos & derivados , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Eptifibatida/administración & dosificación , Eptifibatida/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Infusiones Intravenosas , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/uso terapéutico , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Método Simple Ciego , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Terapia Trombolítica/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Incidencia , AdultoRESUMEN
BACKGROUND: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation. METHODS: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits. RESULTS: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period. CONCLUSION: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses. TRIAL REGISTRATION: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021.
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Inyecciones Intravítreas , Proteínas Recombinantes de Fusión , Hemorragia Retiniana , Activador de Tejido Plasminógeno , Agudeza Visual , Vitrectomía , Humanos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Hemorragia Retiniana/tratamiento farmacológico , Hemorragia Retiniana/etiología , Hemorragia Retiniana/diagnóstico , Agudeza Visual/fisiología , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Anciano , Vitrectomía/métodos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Terapia Combinada , Tomografía de Coherencia Óptica , Estudios de Seguimiento , Quimioterapia Combinada , Angiografía con FluoresceínaRESUMEN
BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.
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Fibrinolíticos , Prótesis Valvulares Cardíacas , Terapia Trombolítica , Trombosis , Humanos , Femenino , Masculino , Estudios Prospectivos , Terapia Trombolítica/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Persona de Mediana Edad , Trombosis/tratamiento farmacológico , Trombosis/etiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Anciano , Estudios de Cohortes , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Enfermedad AgudaRESUMEN
BACKGROUND: Tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke. Although initial improvement is observed when administered for branch atheromatous disease (BAD), some cases subsequently worsen. Clinical data on the characteristics of these patients is lacking, and the benefits of tPA are unclear. OBJECTIVE: To analyze rebound cases and elucidate the clinical characteristics and outcomes associated with tPA administration in BAD. METHODS: This multicenter retrospective study was conducted in Japan. Worsening after initial improvement of a condition is termed as rebound, and such cases were compared with other types of ischemic stroke in patients with and without rebound. The characteristics of patients with BAD who rebounded were examined. RESULTS: The study included 93 patients. Among the patients who were administered tPA, the NIHSS scores at 24 h and 7 days post-tPA were significantly higher in patients with BAD than in patients with other types of infarcts. The group with BAD exhibited a significantly higher rate of rebound than other groups (37.5 % vs. 0 %, P < 0.001). However, no differences were observed in outcomes between patients who experienced rebound after tPA administration and those who did not. CONCLUSIONS: Reevaluation and changing the strategy of tPA use in patients with BAD may be necessary. However, this study does not totally discourage its use, as specific patients can benefit.
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Fibrinolíticos , Activador de Tejido Plasminógeno , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Masculino , Femenino , Anciano , Estudios Retrospectivos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Japón , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/diagnóstico por imagenRESUMEN
Venous thromboembolism (VTE) has been occurring frequently in human society. There is an urgent need to study the influence of several factors on thrombolytic therapy, such as the effects of vascular pressure levels (VPL) and the drug injection time (DIT). Considering blood as a non-Newtonian fluid, valve as a hyperelastic material, and thrombus as a porous medium, a new numerical simulation model of biofluid mechanics incorporating fluid-solid coupling phenomena and biochemical substance reactions is established based on the N-S equations and the convection-diffusion reaction equations. Then, a unique in vitro experimental platform is established to verify the correctness of the constructed mathematical model. The results showed that vascular compression resulted in significant differences in blood flow status localized within the vessel. Vascular compression causes the blood boosting index to fluctuate and the valve displacement values are 135% and 158% greater than the lower VPL, respectively. At the same time, vascular compression weakened vortex intensity, accelerated material transport and response, and improved the treatment. Compared with low VPL, the therapeutic efficacy increased by 7% and 15%, respectively. In addition, when the dose of the drug is high, different injection times can increase the therapeutic effect to different degrees, with a maximum difference of 12%. Our in vitro experiments are similar to the results obtained by numerical simulation, which can verify the reliability of numerical simulation. The computational model proposed and the experimental platform designed in this study have the potential to assist in clinical medication prediction in different venous thromboembolism patients.
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Simulación por Computador , Modelos Cardiovasculares , Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Tromboembolia Venosa/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Presión Sanguínea/efectos de los fármacosRESUMEN
BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Recuperación de la Función , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Pronóstico , Índice de Severidad de la Enfermedad , Estado Funcional , Evaluación de la Discapacidad , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: This study aimed to externally validate different predictive scores for symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT), with a particular focus on their predictive abilities in Asian stroke patients. METHODS: We retrospectively enrolled stroke patients who received a standard dose of alteplase within 4.5â¯hours from symptom onset at the First Affiliated Hospital of Dalian Medical University from July 2010 to August 2023. SICH was defined as the hemorrhagic transformation detected on the head CT scan completed within 48â¯h post-IVT, accompanied by a clinical deterioration of at least a 4-point increase in NIHSS score. Predictive abilities of the HAT, MSS, SEDAN, SPAN-100, and GRASPS scores were tested. Discrimination and calibration were performed using the area under the receiver operating characteristic curve (ROC-AUC), DeLong test, and Hosmer-Lemeshow (H-L) goodness-of-fit test. RESULTS: The study included 1007 stroke patients, of whom 31 (3.08â¯%) developed SICH. ROC-AUCs for predicting SICH were: 0.796 (95â¯%CI: 0.726-0.866) for the GRASPS score, 0.724 (95â¯%CI: 0.644-0.804) for the MSS score, 0.715 (95â¯%CI: 0.619-0.811) for the SEDAN score, 0.714 (95â¯%CI: 0.611-0.817) for the HAT score, and 0.605 (95â¯%CI: 0.491-0.720) for the SPAN-100 score (all P < 0.05). DeLong tests showed that the GRASPS score demonstrated significantly better discrimination than the MSS score (P = 0.010), the SEDAN score (P = 0.009), the HAT score (P = 0.049), and the SPAN-100 score (P = 0.000). H-L tests indicated good calibrations which were ranked HAT > SEDAN > MSS > SPAN-100 > GRASPS scores. CONCLUSION: The GRASPS score showed reasonable predictive ability for SICH, indicating its potential utility for Asian stroke patients receiving IVT.
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Fibrinolíticos , Hemorragias Intracraneales , Accidente Cerebrovascular , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Hemorragias Intracraneales/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Estudios Retrospectivos , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Pueblo Asiatico , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Administración IntravenosaRESUMEN
BACKGROUND: Endovascular treatment (EVT) has been demonstrated to be effective for patients with tandem occlusion. The efficacy and safety of intravenous thrombolysis before EVT in patients with tandem occlusion remain debatable. METHODS AND RESULTS: We conducted a systematic review and meta-analysis with PubMed, EMBASE, and the Cochrane Library from inception to September 2023. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. The secondary outcomes included the successful recanalization rate, symptomatic intracerebral hemorrhage, and mortality at 90 days. In total, 9 studies with 1838 enrolled participants were identified. Our results showed that, compared with treatment with EVT alone, intravenous thrombolysis before EVT was associated with a greater proportion of functional independence at 90 days (odds ratio [OR], 1.39 [95% CI, 1.14-1.69]; P=0.001), a greater rate of successful recanalization (OR, 1.45 [95% CI, 1.11-1.89]; P=0.007) and decreased mortality (OR, 0.68 [95% CI, 0.50-0.93]; P=0.02). Furthermore, there was no significant difference in symptomatic intracerebral hemorrhage between the intravenous thrombolysis plus EVT group and the EVT alone group (OR, 1.16 [95% CI, 0.79-1.70]; P=0.45). CONCLUSIONS: In patients with acute ischemic stroke and tandem occlusion, intravenous thrombolysis before EVT was associated with a greater rate of favorable functional outcomes and successful recanalization and a lower mortality rate without an increased risk of symptomatic intracerebral hemorrhage compared with patients receiving EVT alone.
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Procedimientos Endovasculares , Fibrinolíticos , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Resultado del Tratamiento , Administración IntravenosaRESUMEN
AIMS: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors. MAIN METHODS: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors. KEY FINDINGS: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer. SIGNIFICANCE: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.
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Heparina , Neoplasias , Subtilisinas , Trombosis , Animales , Subtilisinas/administración & dosificación , Ratones , Trombosis/tratamiento farmacológico , Inyecciones Intravenosas , Heparina/administración & dosificación , Neoplasias/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Electricidad Estática , Cobayas , Masculino , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Liposomas , HumanosRESUMEN
Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.
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Accidente Cerebrovascular Isquémico , Trombectomía , Terapia Trombolítica , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Trombectomía/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Terapia Trombolítica/métodos , Terapia Combinada , Resultado del Tratamiento , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Puntaje de PropensiónRESUMEN
Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials.
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Fibrinolíticos , Hemotórax , Terapia Trombolítica , Activador de Tejido Plasminógeno , Activador de Plasminógeno de Tipo Uroquinasa , Animales , Conejos , Hemotórax/etiología , Hemotórax/terapia , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Terapia Trombolítica/métodos , Modelos Animales de Enfermedad , Pleura/efectos de los fármacosRESUMEN
BACKGROUND: Complicated pleural infection comprises of complex effusions and empyema. When tube thoracostomy is ineffective, treatment options include surgical drainage, deloculation and decortication or intrapleural fibrinolysis. We performed a systematic review and meta-analysis to examine which technique is superior in treating complicated pleural infections. METHODS: PubMed, MEDLINE and EMBASE databases were searched for studies published between January 2000 to July 2023 comparing surgery and intrapleural fibrinolysis for treatment of complicated pleural infection. The primary outcome was treatment success. Secondary outcomes included hospital length of stay, chest drain duration and in-hospital mortality. RESULTS: Surgical management of complicated pleural infections was more likely to be successful than intrapleural fibrinolysis (RR 1.18; 95% CI 1.02, 1.38). Surgical intervention group benefited from statistically significant shorter hospital length of stay (MD: 3.85; 95% CI 1.09, 6.62) and chest drain duration (MD: 3.42; 95% CI 1.36, 5.48). There was no observed difference between in-hospital mortality (RR: 1.00; 95% CI 0.99, 1.02). CONCLUSION: Surgical management of complicated pleural infections results in increased likelihood of treatment success, shorter chest drain duration and hospital length of stay in the adult population compared with intrapleural fibrinolysis. In-hospital mortality did not differ. Large cohort and randomized research need to be conducted to confirm these findings.
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Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Empiema Pleural/cirugía , Empiema Pleural/mortalidad , Empiema Pleural/diagnóstico , Resultado del Tratamiento , Mortalidad Hospitalaria , Drenaje/métodos , Tiempo de Internación , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinólisis/efectos de los fármacos , Derrame Pleural/cirugía , Derrame Pleural/terapiaRESUMEN
OBJECTIVE: To compare the effectiveness and safety of the use of non-immunogenic staphylokinase (NS) and alteplase (AP) for intravenous thrombolysis (IT) for ischemic stroke (IS) in real clinical practice at a regional vascular center. MATERIAL AND METHODS: Data from 100 patients with IS who received IT with NS and 100 patients who received IT with AP for the period 2022-2023 were analyzed. The groups were comparable on sociodemographic parameters, cardiovascular risk factors and diseases, and stroke characteristics. RESULTS: Door-to-needle time was 17 (13-22) min in the NS group and 38 (33-42) min in the AP group (p<0.001). During control neuroimaging, a cerebral infarction was detected in 46% of patients in the NS group and 61% of patients in the AP group (OR 0.479 [0.263; 0.875], p=0.035). When performing IT with NS, an NIHSS score of 0 points (no neurological deficit) was observed twice as often (OR 2.202 [1.079; 4.504], p=0.023). The incidence of hemorrhagic transformation, including symptomatic, as well as hospital mortality did not differ. CONCLUSION: IT with NS is associated with a lower probability of cerebral infarction and greater positive dynamics of the neurological status in comparison with the use of AP already within the first stage of treatment and rehabilitation.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Sistema de Registros , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Terapia Trombolítica/métodos , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Resultado del Tratamiento , Metaloendopeptidasas , Administración IntravenosaRESUMEN
INTRODUCTION: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. METHODS: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. RESULTS: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. CONCLUSION: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. LEVEL OF EVIDENCE: Level I, network meta-analysis of RCTs.
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Artroplastia de Reemplazo de Rodilla , Teorema de Bayes , Metaanálisis en Red , Tromboembolia Venosa , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificación , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Dabigatrán/uso terapéutico , Dabigatrán/administración & dosificación , Pirazoles/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Embolia Pulmonar/prevención & control , Embolia Pulmonar/etiología , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Hemorragia/inducido químicamente , Femenino , Fondaparinux/uso terapéutico , Piridinas , TiazolesRESUMEN
OBJECTIVE: To investigate the effect of hospital working hours on outcomes of patients with acute ischemic stroke 3 months after receiving alteplase intravenous thrombolysis. METHODS: A retrospective analysis was performed on 254 individuals with acute ischemic stroke who received alteplase intravenous thrombolysis between January 2018 and December 2020 either during peak hospital working hours (08:00-17:59; Group A) or off-peak hours (18:00-07:59 the following day; Group B). Patients were also categorized according to which of four peak/off-peak-hour periods they received treatment in: Group 1 (08:00-11:59), Group 2 (12:00-17:59), Group 3 (18:00-21:59), Group 4 (22:00-07:59 the following day). Baseline data and 3-month prognosis were compared across groups. Logistic regression analysis was used to investigate the correlation between hospital working hours and 3-month prognosis. RESULTS: There were no significant differences in door-to-needle time, onset-to-needle time, 24-hour National Institutes of Health Stroke Scale (NIHSS) score, 7-day NIHSS score or Modified Rankin Score between Groups 1 to 4 or between Groups A and B. Whether treatment was administered during peak or off-peak hours did not significantly affect 3-month prognosis. CONCLUSION: At this hospital, differences in the time at which stroke patients were treated were not associated with outcomes.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Tejido Plasminógeno/administración & dosificación , Femenino , Masculino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Persona de Mediana Edad , Anciano , Terapia Trombolítica/métodos , Estudios Retrospectivos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Administración Intravenosa , Resultado del Tratamiento , Factores de Tiempo , Tiempo de Tratamiento/estadística & datos numéricos , Anciano de 80 o más AñosRESUMEN
According to the importance of time in treatment of thrombosis disorders, faster than current treatments are required. For the first time, this research discloses a novel strategy for rapid dissolution of blood clots by encapsulation of a fibrinolytic (Reteplase) into a Thrombin sensitive shell formed by polymerization of acrylamide monomers and bisacryloylated peptide as crosslinker. Degradability of the peptide units in exposure to Thrombin, creates the Thrombin-sensitive Reteplase nanocapsules (TSRNPs) as a triggered release system. Accelerated thrombolysis was achieved by combining three approaches including: deep penetration of TSRNPs into the blood clots, changing the clot dissolution mechanism by altering the distribution pattern of TSRNPs to 3D intra-clot distribution (based on the distributed intra-clot thrombolysis (DIT) model) instead of peripheral and unidirectional distribution of unencapsulated fibrinolytics and, enzyme-stimulated release of the fibrinolytic. Ex-vivo study was carried out by an occluded tube model that mimics in-vivo brain stroke as an emergency situation where faster treatment in short time is a golden key. In in vivo, efficacy of the developed formulation was confirmed by PET scan and laser Doppler flowmetry (LDF). As the most important achievements, 40.0 ± 0.7 (n = 3) % and 37.0 ± 0.4 (n = 3) % reduction in the thrombolysis time (faster reperfusion) were observed by ex-vivo and in-vivo experiments, respectively. Higher blood flow and larger digestion mass of clot at similar times in comparison to non-encapsulated Reteplase were observed that means more effective thrombolysis by the developed strategy.
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Fibrinolíticos , Trombina , Terapia Trombolítica , Activador de Tejido Plasminógeno , Fibrinolíticos/administración & dosificación , Fibrinolíticos/química , Fibrinolíticos/farmacología , Animales , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Trombina/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Péptidos/química , Péptidos/administración & dosificación , Polímeros/química , Trombosis/tratamiento farmacológico , Masculino , Liberación de Fármacos , Nanopartículas/químicaRESUMEN
OBJECTIVES: As indications for acute ischemic stroke treatment expand, it is unclear whether disparities in treatment utilization and outcome still exist. The main objective of this study was to investigate disparities in acute ischemic stroke treatment and determine impact on outcome. MATERIALS AND METHODS: Retrospective observational cohort study of consecutive ischemic stroke admissions to a comprehensive stroke center from 2012-2021 was performed. Primary exposure was intravenous thrombolysis and/or endovascular thrombectomy. Primary end points were discharge modified Rankin Scale, home disposition, and expired/hospice. Multivariable logistic regression analyses were conducted to elucidate disparities in treatment utilization and determine impact on outcome. RESULTS: Of 517,615 inpatient visits, there were 7,540 (1.46 %) ischemic stroke admissions, increasing from 1.14 % to 1.79 % from 2012-2021. Intravenous thrombolysis significantly decreased from 14.4 % to 9.8 % while endovascular thrombectomy significantly increased from 0.8 % to 10.5 %. Both intravenous thrombolysis and endovascular thrombectomy increased odds of discharge home and modified Rankin Scale 0-2, and thrombectomy decreased odds of expired/hospice. After adjusting for covariates, decreased odds of thrombectomy was associated with Medicaid insurance (Odds Ratio [95 % Confidence Interval] 0.55 [0.32-0.93]), age 80+ (0.49 [0.35-0.69]), prior stroke (0.49 [0.31-0.77]), and diabetes mellitus (0.55 [0.39-0.79]), while low median household income (<$80,000/year) increased odds of no acute treatment (1.34 [1.16-1.56]). No sex or racial disparities were observed. Medicaid and low-income were not associated with worse clinical outcomes. CONCLUSIONS: Less endovascular thrombectomy occurred in Medicaid, older, prior stroke, and diabetic patients, while low-income was associated with no treatment. The observed socioeconomic disparities did not impact discharge outcome.
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Procedimientos Endovasculares , Fibrinolíticos , Disparidades en Atención de Salud , Accidente Cerebrovascular Isquémico , Trombectomía , Terapia Trombolítica , Humanos , Terapia Trombolítica/tendencias , Terapia Trombolítica/efectos adversos , Masculino , Femenino , Trombectomía/tendencias , Trombectomía/efectos adversos , Anciano , Estudios Retrospectivos , Disparidades en Atención de Salud/tendencias , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Resultado del Tratamiento , Persona de Mediana Edad , Factores de Tiempo , Anciano de 80 o más Años , Fibrinolíticos/administración & dosificación , Procedimientos Endovasculares/tendencias , Procedimientos Endovasculares/efectos adversos , Factores de Riesgo , Evaluación de la Discapacidad , Alta del Paciente/tendencias , Estados Unidos/epidemiología , Medicaid/tendencias , Medición de Riesgo , Pautas de la Práctica en Medicina/tendenciasRESUMEN
BACKGROUND: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS. METHODS AND RESULTS: This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale [mRS] score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% [95% CI -2.0% to 6.7%]; P=0.295; risk ratio, 1.03 [95% CI 0.98-1.08]; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 [95% CI 0.41-0.79]; P<0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% [95% CI 13.1%-28.6%]; risk ratio, 1.59 [95% CI 1.34-1.89]; both P<0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 [95% CI 0.08-0.90]; P=0.034). There were no differences in safety outcomes. CONCLUSIONS: According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.