RESUMO
BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).
Assuntos
Anticoagulantes , Fibrilação Atrial , Inibidores do Fator Xa , Cardiopatia Reumática , Rivaroxabana , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/etiologia , Ecocardiografia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Cardiopatia Reumática/complicações , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/diagnóstico por imagem , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos , Varfarina/uso terapêuticoRESUMO
SOURCE CITATION: Joosten LP, van Doorn S, van de Ven PM, et al. Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the FRAIL-AF randomized controlled trial. Circulation. 2024;149:279-289. 37634130.
Assuntos
Anticoagulantes , Fibrilação Atrial , Hemorragia , Vitamina K , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Hemorragia/induzido quimicamente , Vitamina K/antagonistas & inibidores , Idoso Fragilizado , Substituição de Medicamentos , Masculino , Idoso de 80 Anos ou mais , Feminino , Fragilidade , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).
Assuntos
4-Hidroxicumarinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Substituição da Valva Aórtica Transcateter , Vitamina K/antagonistas & inibidores , 4-Hidroxicumarinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Mortalidade , Fenindiona/análogos & derivados , Fenindiona/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Tromboembolia/prevenção & controle , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
AIM: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D. MATERIALS AND METHODS: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow-up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower-limb amputation (LLA) or lower-limb revascularization. LLA and lower-limb revascularization were considered individually as secondary outcomes. RESULTS: During a 7-year median follow-up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88-2.31]. During the study period, LLA and lower-limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04-3.47)], but not lower-limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59-1.97)]. CONCLUSIONS: In this prospective study, we did not observe any excess risk of PAD requiring lower-limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation.
Assuntos
Amputação Cirúrgica , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas , Doença Arterial Periférica , Vitamina K , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Feminino , Masculino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidores , Amputação Cirúrgica/estatística & dados numéricos , França/epidemiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/prevenção & controle , Fatores de Risco , Seguimentos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , IncidênciaRESUMO
ABSTRACT: Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.
Assuntos
Anticoagulantes , Síndrome Antifosfolipídica , Inibidores do Fator Xa , Hemorragia , Pirazóis , Piridonas , Vitamina K , Varfarina , Humanos , Feminino , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Masculino , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Pessoa de Meia-Idade , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Vitamina K/antagonistas & inibidores , Adulto , Resultado do Tratamento , Fatores de Risco , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Varfarina/efeitos adversos , Varfarina/uso terapêutico , Varfarina/administração & dosagem , Fatores de Tempo , Medição de Risco , Recidiva , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/epidemiologia , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/epidemiologia , AVC Isquêmico/prevenção & controle , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologiaRESUMO
BACKGROUND: This study aimed to evaluate the mandibular bone structure of patients using oral anticoagulants (OACs) vitamin K antagonist drugs (warfarin) and other OACs including direct oral anticoagulants [(DOACs) apixaban, rivaroxaban, dabigatran, edoxaban]. Analyses were based upon the fractal dimension (FD), the panoramic mandibular index (PMI) and the Klemetti index (KI), which is also known as the mandibular cortical index (MCI). METHODOLOGY: Ninety participants were divided into three groups: group 1: 30 systemically healthy individuals who had not used any anticoagulants before, group 2: 30 individuals using warfarin, and group 3: 30 individuals using DOACs. FD was used to analyze trabecular bone architecture in the condyle, angle, and two sites in the alveolar bone. PMI was used to evaluate the quantity of cortical bone and KI was used to evaluate the cortical bone quality. RESULTS: There was no difference between the groups regarding FD analysis and KI; however, a difference was found between groups 1, 2, and 3 in the PMI (P≤ 0.001). The PMI in group 1 was higher than in groups 2 and 3. CONCLUSION: Mandibular radiomorphometric indices can be used on panoramic radiographs to evaluate the quantity of mandibular cortical bone in patients using oral anticoagulants.
Assuntos
Anticoagulantes , Osso Esponjoso , Osso Cortical , Dabigatrana , Mandíbula , Rivaroxabana , Varfarina , Humanos , Mandíbula/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Dabigatrana/administração & dosagem , Rivaroxabana/administração & dosagem , Varfarina/administração & dosagem , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Cortical/diagnóstico por imagem , Osso Cortical/efeitos dos fármacos , Piridonas/administração & dosagem , Adulto , Pirazóis/administração & dosagem , Tiazóis/administração & dosagem , Idoso , Vitamina K/antagonistas & inibidores , Piridinas/administração & dosagem , Radiografia Panorâmica , Administração Oral , Densidade Óssea/efeitos dos fármacos , Inibidores do Fator Xa/administração & dosagemRESUMO
BACKGROUND: In patients undergoing revascularization for peripheral arterial disease (PAD), low-dose Factor Xa inhibitors (FXaI) taken with aspirin improved limb and cardiovascular outcomes compared to aspirin alone. Furthermore, in atrial fibrillation and venous thromboembolism, FXaI are recommended over vitamin K antagonists (VKA) for chronic anticoagulation. While studies have evaluated different perioperative anticoagulation regimens in patients treated for PAD, the optimal regimen for chronic anticoagulation in patients with PAD undergoing peripheral vascular intervention (PVI) has not been determined. This analysis compares outcomes of patients after PVI that require chronic anticoagulation with FXaI and VKA. METHODS: The Vascular Quality Initiative-PVI database was used. Patients consistently treated with FXaI or VKA before the procedure, at discharge, and on long-term follow-up were defined as those receiving chronic anticoagulation. Patient demographics, procedural details, and perioperative and long-term outcomes were compared between FXaI and VKA groups. RESULTS: A total of 109,268 patients were analyzed, and 6,885 were chronically anticoagulated with FXaI (N = 2,427) or VKA (N = 4,458). Patients anticoagulated with VKA were more frequently males (65.3% vs. 61.0%, P < 0.001) with end-stage renal disease (9.7% vs. 4.6%, P < 0.001) and more likely to be treated for chronic limb-threatening ischemia (58.1% vs. 52.7%, P < 0.001). Rates of hematoma following PVI were significantly higher in patients taking VKA compared to FXaI (3.5% vs. 1.9%, P < 0.001). Multivariable logistic regression analysis showed that VKA were associated with increased perioperative hematoma than FXaI (odds ratio = 1.89 [1.30-2.82]). Compared to patients taking VKA, those receiving FXaI had lower rates of major amputation (6.7% vs. 8.4%, P = 0.020) and mortality (7.6% vs. 15.2%, P ≤ 0.001). Using Kaplan-Meier analysis, patients consistently anticoagulated with FXaI had improved amputation-free survival after PVI. Adjusting for significant patient and procedural characteristics, Cox proportional hazard regression demonstrated that there is an increased risk for major amputation or mortality in patients using VKA compared to FXaI (hazard ratio 1.61, [1.36-1.90]). CONCLUSIONS: Chronic anticoagulation with FXaI as compared to VKA was associated with superior perioperative and long-term outcomes in patients with PAD undergoing PVI. FXaI should be the preferred agents over VKA for chronic anticoagulation in patients with PAD undergoing PVI.
Assuntos
Anticoagulantes , Bases de Dados Factuais , Inibidores do Fator Xa , Doença Arterial Periférica , Vitamina K , Humanos , Masculino , Feminino , Idoso , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Fatores de Risco , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidores , Estudos Retrospectivos , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Hemorragia/induzido quimicamente , Esquema de Medicação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Medição de Risco , Salvamento de Membro , Estados Unidos , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
BACKGROUND: This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. METHODS: All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible. RESULTS: Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I2 = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I2 = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I2 = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I2 = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I2 = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I2 = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I2 = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes. CONCLUSIONS: Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.
Assuntos
Inibidores do Fator Xa , Pirazóis , Piridonas , Diálise Renal , Vitamina K , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K/antagonistas & inibidoresRESUMO
OBJECTIVE: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. METHODS: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. RESULTS: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). INTERPRETATION: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88.
Assuntos
Fibrilação Atrial/complicações , Inibidores do Fator Xa/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/etiologia , Vitamina K/antagonistas & inibidoresRESUMO
PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.
Assuntos
Anticoagulantes , Fibrilação Atrial , Acidente Vascular Cerebral , Vitamina K , Humanos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragias Intracranianas/induzido quimicamente , Metanálise em Rede , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Administração OralRESUMO
Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32â¯715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32â¯715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29â¯628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29â¯628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Hemorragias Intracranianas , AVC Isquêmico , Trombectomia , Vitamina K , Idoso , Feminino , Humanos , Masculino , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/mortalidade , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etiologia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/mortalidade , AVC Isquêmico/cirurgia , Estudos Retrospectivos , Trombectomia/efeitos adversos , Trombectomia/métodos , Trombectomia/mortalidade , Resultado do Tratamento , Vitamina K/antagonistas & inibidores , Administração Oral , Mortalidade Hospitalar , Coeficiente Internacional NormatizadoRESUMO
BACKGROUND: In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. METHODS: In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. RESULTS: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. CONCLUSIONS: The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Rim/patologia , Intervenção Coronária Percutânea/métodos , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/farmacologia , Piridonas/farmacologiaRESUMO
BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).
Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversosRESUMO
OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Isquemia Encefálica/complicações , AVC Isquêmico/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Estudos de Coortes , Feminino , Fibrinolíticos/uso terapêutico , Humanos , AVC Isquêmico/complicações , Masculino , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidoresRESUMO
Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.
Assuntos
Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Transtornos Hemorrágicos/induzido quimicamente , Ensaios de Triagem em Larga Escala/métodos , Vitamina K/metabolismo , 4-Hidroxicumarinas/efeitos adversos , 4-Hidroxicumarinas/isolamento & purificação , 4-Hidroxicumarinas/farmacologia , Animais , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Células HEK293 , Células Hep G2 , Humanos , Indenos/efeitos adversos , Indenos/isolamento & purificação , Indenos/farmacologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Uso Off-Label , Vitamina K/efeitos adversos , Vitamina K/antagonistas & inibidores , Vitamina K/isolamento & purificação , Vitamina K/farmacologia , Vitamina K Epóxido Redutases/antagonistas & inibidores , Vitamina K Epóxido Redutases/metabolismoRESUMO
STUDY OBJECTIVE: To determine if a fixed dose of 1000 IU of 4-factor prothrombin complex concentrate (4F-PCC) is as effective as traditional variable dosing based on body weight and international normalized ratio (INR) for reversal of vitamin K antagonist (VKA) anticoagulation. METHODS: In this open-label, multicenter, randomized clinical trial, patients with nonintracranial bleeds requiring VKA reversal with 4F-PCC were allocated to either a 1,000-IU fixed dose of 4F-PCC or the variable dose. The primary outcome was the proportion of patients with effective hemostasis according to the International Society of Thrombosis and Haemostasis definition. The design was noninferiority with a lower 95% confidence interval of no more than -6%. When estimating sample size, we assumed that fixed dosing would be 4% superior. RESULTS: From October 2015 until January 2020, 199 of 310 intended patients were included before study termination due to decreasing enrollment rates. Of the 199 patients, 159 were allowed in the per-protocol analysis. Effective hemostasis was achieved in 87.3% (n=69 of 79) in fixed compared to 89.9% (n=71 of 79) in the variable dosing cohort (risk difference 2.5%, 95% confidence interval -13.3 to 7.9%, P=.27). Median door-to-needle times were 109 minutes (range 16 to 796) in fixed and 142 (17 to 1076) for the variable dose (P=.027). INR less than 2.0 at 60 minutes after 4F-PCC infusion was reached in 91.2% versus 91.7% (P=1.0). CONCLUSION: The large majority of patients had good clinical outcome after 4F-PCC use; however, noninferiority of the fixed dose could not be demonstrated because the design assumed the fixed dose would be 4% superior. Door-to-needle time was shortened with the fixed dose, and INR reduction was similar in both dosing regimens.
Assuntos
Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemostáticos/administração & dosagem , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown. METHODS: In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding. RESULTS: Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; P=0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; P=0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; P=0.02) in the pooled rivaroxaban groups. CONCLUSIONS: In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Oral Anticoagulation in Hemodialysis, NCT03799822.
Assuntos
Antifibrinolíticos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Diálise Renal , Rivaroxabana/uso terapêutico , Vitamina K 2/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/efeitos adversos , Fibrilação Atrial/complicações , Doenças Cardiovasculares/etiologia , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Mortalidade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Vitamina K/antagonistas & inibidores , Vitamina K 2/efeitos adversos , Vitamina K 2/uso terapêuticoRESUMO
Importance: Pulmonary embolism (PE) is characterized by occlusion of blood flow in a pulmonary artery, typically due to a thrombus that travels from a vein in a lower limb. The incidence of PE is approximately 60 to 120 per 100â¯000 people per year. Approximately 60â¯000 to 100â¯000 patients die from PE each year in the US. Observations: PE should be considered in patients presenting with acute chest pain, shortness of breath, or syncope. The diagnosis is determined by chest imaging. In patients with a systolic blood pressure of at least 90 mm Hg, the following 3 steps can be used to evaluate a patient with possible PE: assessment of the clinical probability of PE, D-dimer testing if indicated, and chest imaging if indicated. The clinical probability of PE can be assessed using a structured score or using clinical gestalt. In patients with a probability of PE that is less than 15%, the presence of 8 clinical characteristics (age <50 years, heart rate <100/min, an oxygen saturation level of > 94%, no recent surgery or trauma, no prior venous thromboembolism event, no hemoptysis, no unilateral leg swelling, and no estrogen use) identifies patients at very low risk of PE in whom no further testing is needed. In patients with low or intermediate clinical probability, a D-dimer level of less than 500 ng/mL is associated with a posttest probability of PE less than 1.85%. In these patients, PE can be excluded without chest imaging. A further refinement of D-dimer threshold is possible in patients aged 50 years and older, and in patients with a low likelihood of PE. Patients with a high probability of PE (ie, >40% probability) should undergo chest imaging, and D-dimer testing is not necessary. In patients with PE and a systolic blood pressure of 90 mm Hg or higher, compared with heparin combined with a vitamin K antagonist such as warfarin followed by warfarin alone, direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, are noninferior for treating PE and have a 0.6% lower rate of bleeding. In patients with PE and systolic blood pressure lower than 90 mm Hg, systemic thrombolysis is recommended and is associated with an 1.6% absolute reduction of mortality (from 3.9% to 2.3%). Conclusions and Relevance: In the US, PE affects approximately 370â¯000 patients per year and may cause approximately 60â¯000 to 100â¯000 deaths per year. First-line therapy consists of direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg.
Assuntos
Anticoagulantes , Embolia Pulmonar , Doença Aguda , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina/uso terapêutico , Humanos , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/terapia , Risco , Rivaroxabana/uso terapêutico , Estados Unidos/epidemiologia , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêuticoRESUMO
OBJECTIVE: Epistaxis is the most common otolaryngological emergency and up to one third of patients in treated on an inpatient basis take oral anticoagulants (OAC). Direct oral anticoagulants (DOAC), an OAC subgroup, have been on the market since 2010 and are being increasingly prescribed due to the cardiological and haematological guidelines that favour them over vitamin K antagonists (VKA), the older of the OAC subgroups. The present study aims to investigate which subgroup of epistaxis patients taking OACs has a more favourable outcome. DESIGN/SETTING: A systematic review and meta-analysis were performed according to the PRISMA 2020 statement using the PubMed and Cochrane Library databases. Continuous data were analysed and standardised mean difference (SMD) was calculated according to Hedges' g. Dichotomous data were analysed, and the Mantel-Haenszel method was applied to establish the odds ratio (OR). Heterogeneity was assessed according to the I2 statistics. MAIN OUTCOME/RESULTS: A total of eight reports covering 1390 patients were included in the final synthesis. The pooled analysis demonstrated significantly shorter hospital stays in the DOAC group (SMD = -0.22, 95% CI-0.42 to -0.02, p = .03) and a significantly higher rate of posterior bleeding in the VKA group (OR = .39, 95% CI 0.23 to 0.68, p = .001). No statistically significant differences with regard to recurrence rates, admission rates, the need for transfusion or surgical intervention (p = .57, .12, .57 and .38 respectively) were found. CONCLUSION: According to this meta-analysis, epistaxis patients taking DOACs have a more favourable outcome than patients taking VKAs.
Assuntos
Anticoagulantes/efeitos adversos , Epistaxe/induzido quimicamente , Vitamina K/efeitos adversos , Vitamina K/antagonistas & inibidores , Administração Oral , Hospitalização , HumanosRESUMO
BACKGROUND: In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo. METHODS: In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y12 inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo. RESULTS: Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98]). CONCLUSIONS: In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y12 inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.