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1.
Thromb Res ; 197: 44-47, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33181470

RESUMO

COVID-19 has been associated with an increased risk of thrombotic events; however, the reported incidence of deep vein thrombosis varies depending, at least in part, on the severity of the disease. Aim of this prospective, multicenter, observational study was to investigate the incidence of lower limb deep vein thrombosis as assessed by compression ultrasound in consecutive patients admitted to three pulmonary medicine wards designated to care for patients with COVID-19 related pneumonia, with or without respiratory failure but not requiring admission to an intensive care unit. Consecutive patients admitted between March 27 and May 6, 2020 were enrolled. Patients were excluded if they were less than 18-year-old or if compression ultrasound could not be performed for any reason. Patients were assessed at admission (t0) and after 7 days (t1). Major and non-major clinically relevant bleedings were recorded. Sixty-eight patients were enrolled. Two were excluded due to anatomical abnormalities that prevented compression ultrasound; sixty patients were retested at (t1). All patients were started on antithrombotic prophylaxis, unless therapeutic anticoagulation was required. Deep vein thrombosis as assessed by compression ultrasound was observed in 2 patients (3%); one of them was later deemed to represent a previous episode. No new episodes were detected at t1. One major and 2 non-major clinically relevant bleedings were observed. In the setting of patients with COVID-related pneumonia not requiring admission to an intensive care unit, the incidence of deep vein thrombosis is low and our data support not screening asymptomatic patients.


Assuntos
/complicações , Instituições para Cuidados Intermediários/estatística & dados numéricos , Tromboflebite/etiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Comorbidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Pressão , Estudos Prospectivos , Embolia Pulmonar/etiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboflebite/diagnóstico por imagem , Tromboflebite/epidemiologia , Ultrassonografia/métodos
2.
J Cardiothorac Vasc Anesth ; 35(2): 389-397, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32994131

RESUMO

OBJECTIVE: To explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)-assisted patients with coronavirus disease 2019 (COVID-19). DESIGN: Single-center, retrospective observation of a series of patients. PARTICIPANTS: Laboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20-May 20, 2020. INTERVENTIONS: This study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support. MEASUREMENTS AND MAIN RESULTS: Eight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8). CONCLUSIONS: Hypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.


Assuntos
Anticoagulantes/uso terapêutico , Oxigenação por Membrana Extracorpórea , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , /diagnóstico por imagem , Cuidados Críticos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Insuficiência Respiratória/diagnóstico por imagem , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Trombose/epidemiologia , Tomografia Computadorizada por Raios X , Traqueia/lesões
4.
J Stroke Cerebrovasc Dis ; 30(1): 105420, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33161351

RESUMO

BACKGROUND: Hyper-responsiveness to clopidogrel abnormally inhibits platelet aggregation and increases hemorrhagic complications. The present study investigated clinical factors related to clopidogrel hyper-responsiveness in neuro-interventional procedures. METHODS: Two hundred twenty-four patients receiving clopidogrel for coil embolization to treat unruptured cerebral aneurysm or carotid artery stenting to treat carotid artery stenosis at the internal carotid artery origin were retrospectively reviewed for their P2Y12 reactivity unit (PRU) values and clinical characteristics. Hyper-responsiveness to clopidogrel was defined as a PRU of <95. RESULTS: The mean PRU was 218.2 ± 77.8. Hyper-responsiveness to clopidogrel was observed in 12 patients (5.4%). Hyper-responsiveness was observed in younger patients, patients with a lower concentration of hemoglobin A1c, and patients with a higher low-density lipoprotein cholesterol (LDL-C) concentration compared with non-hyper-responsive patients (P = 0.01, P < 0.01, P < 0.01, respectively). On analysis of concomitant drugs, the patients in the hyper-responsive group were less frequently administered calcium channel blockers (CCBs) compared with the non-hyper-responsive group (P = 0.01). No significant differences in the usage of proton pump inhibitors or statins were observed. A LDL-C concentration of >120 mg/dL and no usage of CCBs were significant independent predictors of hyper-responsiveness to clopidogrel with a multivariate analysis (OR; 6.16, 95% CI, 1.57-26.64, P = 0.01, OR; 0.09, 95% CI, 0.01-0.82, P = 0.03, respectively). CONCLUSION: The present study shows that a higher LDL-C concentration and no usage of CCBs are independent predictors of clopidogrel hyper-responsiveness. These results are useful to predict perioperative hemorrhagic complications. Considering dose reduction of clopidogrel or alternative drugs in high risk cases is necessary to prevent perioperative hemorrhagic complications.


Assuntos
Estenose das Carótidas/terapia , Clopidogrel/efeitos adversos , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Hemorragia/induzido quimicamente , Aneurisma Intracraniano/terapia , Inibidores da Agregação de Plaquetas/efeitos adversos , Idoso , Estenose das Carótidas/diagnóstico por imagem , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(49): e23055, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285683

RESUMO

BACKGROUND: The purpose of this meta-analysis is to compare the efficacy and safety of aspirin and rivaroxaban in the prevention of venous thromboembolism (VTE) following either total knee arthroplasty or total hip arthroplasty. METHODS: A comprehensive literature search of several electronic databases (PubMed, Embase, and Web of Science) was conducted to identify relevant studies. Outcomes of interest included VTE rate, deep vein thrombosis (DVT) rate, pulmonary embolism rate, major bleeding events, mortality rate, blood transfusion, and wound complication. Risk ratio (RR) with 95% confidence intervals (95%CIs) were calculated using a fixed-effects model or random-effects model. RESULTS: A total of 8 studies with 97,677 patients met the inclusion criteria and were included in this meta-analysis. Compared with rivaroxaban, aspirin had a significantly higher incidence of DVT (RR = 1.48, 95%CI: 1.27, 1.72; P < .001), and decreased risk of blood transfusion (RR = 0.94, 95%CI: 0.93, 0.94; P < .001). However, there were no significant differences between the 2 drugs in terms of total VTE rate (RR = 1.39%, 95%CI: 0.94, 2.05; P = .101), pulmonary embolism rate (RR = 1.64, 95%CI: 0.92, 2.92; P = .094), mortality rate (RR = 1.13, 95%CI: 0.15, 8.27; P = .907), major bleeding (RR = 1.00, 95%CI: 0.44, 2.27; P = .995), and wound complication rate (RR = 0.37, 95%CI: 0.07, 1.87; P = .229). CONCLUSION: Our results suggested that aspirin and rivaroxaban offered similar effect in the prevention of VTE after total knee arthroplasty or total hip arthroplasty. However, rivaroxaban seemed to have better effect than aspirin in reducing the risk of DVT, and aspirin was safer than rivaroxaban in decreasing the blood transfusion rate.


Assuntos
Anticoagulantes/administração & dosagem , Artroplastia do Joelho/métodos , Aspirina/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Hemorragia/induzido quimicamente , Humanos , Embolia Pulmonar/prevenção & controle , Projetos de Pesquisa , Rivaroxabana/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Trombose Venosa/prevenção & controle
6.
Cochrane Database Syst Rev ; 12: CD012467, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33314078

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a major comorbidity in hospitalised patients. Patients with severe AKI require continuous renal replacement therapy (CRRT) when they are haemodynamically unstable. CRRT is prescribed assuming it is delivered over 24 hours. However, it is interrupted when the extracorporeal circuits clot and the replacement is required. The interruption may impair the solute clearance as it causes under dosing of CRRT. To prevent the circuit clotting, anticoagulation drugs are frequently used. OBJECTIVES: To assess the benefits and harms of pharmacological interventions for preventing clotting in the extracorporeal circuits during CRRT. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We selected randomised controlled trials (RCTs or cluster RCTs) and quasi-RCTs of pharmacological interventions to prevent clotting of extracorporeal circuits during CRRT. DATA COLLECTION AND ANALYSIS: Data were abstracted and assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) with 95% confidence intervals (CI). The primary review outcomes were major bleeding, successful prevention of clotting (no need of circuit change in the first 24 hours for any reason), and death. Evidence certainty was determined using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. MAIN RESULTS: A total of 34 completed studies (1960 participants) were included in this review. We identified seven ongoing studies which we plan to assess in a future update of this review. No included studies were free from risk of bias. We rated 30 studies for performance bias and detection bias as high risk of bias. We rated 18 studies for random sequence generation,ààsix studies for the allocation concealment, three studies for performance bias, three studies for detection bias,à nine studies for attrition bias,à14 studies for selective reporting and nine studies for the other potential source of bias, as having low risk of bias. We identified eight studies (581 participants) that compared citrate with unfractionated heparin (UFH). Compared to UFH, citrate probably reduces major bleeding (RR 0.22, 95% CI 0.08 to 0.62; moderate certainty evidence) and probably increases successful prevention of clotting (RR 1.44, 95% CI 1.10 to 1.87; moderate certainty evidence). Citrate may have little or no effect on death at 28 days (RR 1.06, 95% CI 0.86 to 1.30, moderate certainty evidence). Citrate versus UFH may reduce the number of participants who drop out of treatment due to adverse events (RR 0.47, 95% CI 0.15 to 1.49; low certainty evidence). Compared to UFH, citrate may make little or no difference to the recovery of kidney function (RR 1.04, 95% CI 0.89 to 1.21; low certainty evidence). Compared to UFH, citrate may reduceàthrombocytopenia (RR 0.39, 95% CI 0.14 to 1.03; low certainty evidence). It was uncertain whether citrate reduces a cost to health care services because of inadequate data. For low molecular weight heparin (LMWH) versus UFH, six studies (250 participants) were identified. Compared to LMWH, UFH may reduce major bleeding (0.58, 95% CI 0.13 to 2.58; low certainty evidence). It is uncertain whether UFH versus LMWH reduces death at 28 days or leads to successful prevention of clotting. Compared to LMWH, UFH may reduce the number of patient dropouts from adverse events (RR 0.29, 95% CI 0.02 to 3.53; low certainty evidence). It was uncertain whether UFH versus LMWH leads to the recovery of kidney function because no included studies reported this outcome. It was uncertain whether UFH versus LMWH leads to thrombocytopenia. It was uncertain whether UFH reduces a cost to health care services because of inadequate data. For the comparison of UFH to no anticoagulation, one study (10 participants) was identified. It is uncertain whether UFH compare to no anticoagulation leads to more major bleeding. It is uncertain whether UFH improves successful prevention of clotting in the first 24 hours, death at 28 days, the number of patient dropouts due to adverse events, recovery of kidney function, thrombocytopenia, or cost to health care services because no study reported these outcomes. For the comparison ofàcitrate to no anticoagulation,àno completed study was identified. AUTHORS' CONCLUSIONS: Currently,àavailable evidence does not support the overall superiority of any anticoagulant to another. Compared to UFH, citrate probably reduces major bleeding and prevents clotting and probably has little or no effect on death at 28 days. For other pharmacological anticoagulation methods, there is no available data showing overall superiority to citrate or no pharmacological anticoagulation. Further studies are needed to identify patient populations in which CRRT should commence with no pharmacological anticoagulation or with citrate.


Assuntos
Lesão Renal Aguda/terapia , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Obstrução do Cateter , Terapia de Substituição Renal Contínua/instrumentação , Lesão Renal Aguda/mortalidade , Anticoagulantes/efeitos adversos , Viés , Obstrução do Cateter/etiologia , Ácido Cítrico/administração & dosagem , Ácido Cítrico/efeitos adversos , Terapia de Substituição Renal Contínua/efeitos adversos , Terapia de Substituição Renal Contínua/mortalidade , Filtração/instrumentação , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Rim/fisiologia , Pacientes Desistentes do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica/efeitos dos fármacos , Trombocitopenia/prevenção & controle
7.
Cochrane Database Syst Rev ; 12: CD008500, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33337539

RESUMO

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the third update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis, or an active control intervention. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 3 August 2020. We also searched the reference lists of identified studies and contacted content experts and trialists for relevant references. SELECTION CRITERIA: Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: We extracted data on risk of bias, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. We applied GRADE to assess the certainty of evidence. MAIN RESULTS: We identified six additional randomised controlled trials (3326 participants) for this update, bringing the included study total to 32 (15,678 participants), all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The certainty of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. Thromboprophylaxis with direct oral anticoagulants (direct factor Xa inhibitors apixaban and rivaroxaban) may decrease the incidence of symptomatic VTE (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.18 to 1.06; 3 studies, 1526 participants; low-certainty evidence); and probably increases the risk of major bleeding compared with placebo (RR 1.74, 95% CI 0.82 to 3.68; 3 studies, 1494 participants; moderate-certainty evidence). When compared with no thromboprophylaxis, low-molecular-weight heparin (LMWH) reduced the incidence of symptomatic VTE (RR 0.62, 95% CI 0.46 to 0.83; 11 studies, 3931 participants; high-certainty evidence); and probably increased the risk of major bleeding events (RR 1.63, 95% CI 1.12 to 2.35; 15 studies, 7282 participants; moderate-certainty evidence). In participants with multiple myeloma, LMWH resulted in lower symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83; 1 study, 439 participants; high-certainty evidence), while LMWH probably lowers symptomatic VTE more than aspirin (RR 0.51, 95% CI 0.22 to 1.17; 2 studies, 781 participants; moderate-certainty evidence). Major bleeding was observed in none of the participants with multiple myeloma treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis, but did not report on VTE or major bleeding. When compared with placebo or no thromboprophylaxis, warfarin may importantly reduce symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20; 1 study, 311 participants; low-certainty evidence) and may result in a large increase in major bleeding (RR 3.82, 95% CI 0.97 to 15.04; 4 studies, 994 participants; low-certainty evidence). One study evaluated antithrombin versus no antithrombin in children. This study did not report on symptomatic VTE but did report any VTE (symptomatic and incidental VTE). The effect of antithrombin on any VTE and major bleeding is uncertain (any VTE: RR 0.84, 95% CI 0.41 to 1.73; major bleeding: RR 0.78, 95% CI 0.03 to 18.57; 1 study, 85 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: In ambulatory cancer patients, primary thromboprophylaxis with direct factor Xa inhibitors may reduce the incidence of symptomatic VTE (low-certainty evidence) and probably increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo. LMWH decreases the incidence of symptomatic VTE (high-certainty evidence), but increases the risk of major bleeding (moderate-certainty evidence) when compared with placebo or no thromboprophylaxis. Evidence for the use of thromboprophylaxis with anticoagulants other than direct factor Xa inhibitors and LMWH is limited. More studies are warranted to evaluate the efficacy and safety of primary prophylaxis in specific types of chemotherapeutic agents and types of cancer, such as gastrointestinal or genitourinary cancer.


Assuntos
Assistência Ambulatorial , Anticoagulantes/uso terapêutico , Neoplasias/tratamento farmacológico , Prevenção Primária/métodos , Tromboembolia Venosa/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Antineoplásicos/efeitos adversos , Antitrombinas/uso terapêutico , Viés , Criança , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa/etiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
8.
Ann Intern Med ; 173(12): JC64, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316184

RESUMO

SOURCE CITATION: O'Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y12 inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation. 2020;142:538-45. 32551860.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas , Aspirina/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos
9.
Chirurgia (Bucur) ; 115(6): 798-806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378639

RESUMO

Microthrombi formation in the pulmonary circulation is one of the main pathophysiological mechanisms responsible for the unfavorable respiratory evolution of CoViD-19 patients. Low molecular weight heparin (LMWH) anticoagulant therapy is a major pillar of treatment. But sometimes LMWH causes severe complications that can result in death. This is a retrospective, descriptive study, covering September 2020 and presenting 3 cases of severe hemorrhages followed by death in COVID-19 anticoagulated patients in therapeutic doses with LMWH in the hospital units of origin. Patients had hematomas of the rectus abdominal muscles and hemoperitoneum (2 cases) respectively hematoma of left gluteal muscles (1 case). The 2 patients with hematoma of rectus abdominal muscles were operated. The death occurred between 1-4 days after hospitalization.


Assuntos
Anticoagulantes , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Anticoagulantes/efeitos adversos , Evolução Fatal , Humanos , Estudos Retrospectivos , Resultado do Tratamento
10.
J Med Vasc ; 45(6S): 6S17-6S23, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33276939

RESUMO

Venous thromboembolism (VTE) is a common complication among patients with cancer, associated with significant higher rate of mortality and morbidity. Low-molecular-weight heparin (LMWH) as a single therapeutic is considered as the standard of care for the treatment of acute cancer-associated thrombosis for many years, showing a significant 40% reduction of recurrent VTE (RR: 0.58; 95% CI, 0.43 - 0.77) without a significant increase of major bleeding complications compared to VKA (RR: 1.09; 95% CI 0.55 - 2.12). Based on results analysis studies only including patients with proximal DVT or PE the risk of recurrent VTE was similar in the DOAC and the LMWH (RR 0.68; 95% CI, 0.39 - 1.17) groups, without significantively increasing the risk of either major bleeding (RR = 1.32; 95% CI 0.7 - 2.47) or CRNMB (RR 1.6; 95% 0.99 - 2.6). Compared with LMWH, the risk of major bleeding and clinically relevant-non major bleeding was higher, although non-significantly, with DOACs than with LMWH, underlying that DOACs should be avoided in patients at high risk of bleeding. The higher risk of bleeding reported in DOACs-treated patients appears related to an excess of upper GI bleeding. In addition to GI cancer, other high-risk features associated with bleeding complications are an urothelial cancer, drug-drug interactions and use of anticancer drugs associated with GI toxicity. Overall, DOACs are an effective treatment option, and safe in most cancer patients with acute VTE. Nonetheless, DOACs should be used with caution in cancer patients at high risk for bleeding due to cancer site and stage per se or to cancer treatments.


Assuntos
Anticoagulantes/administração & dosagem , Tomada de Decisão Clínica , Inibidores do Fator Xa/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/sangue , Neoplasias/epidemiologia , Seleção de Pacientes , Embolia Pulmonar/sangue , Embolia Pulmonar/epidemiologia , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Trombose Venosa/sangue , Trombose Venosa/epidemiologia
11.
Pol Merkur Lekarski ; 48(287): 361-364, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33130800

RESUMO

stroke or other thromboembolic complications in patients with atrial fibrillation (AF). On the other hand, dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) represents a cornerstone in the treatment of acute coronary syndrome. Atrial fibrillation is relatively common in patients with coronary artery disease and patients who undergo primary percutaneous coronary interventions (PCI) with stent implantation. They should be on triple antithrombotic therapy (TAT): preferably direct oral anticoagulants (DOAC) plus aspirin plus clopidogrel as it prevents ischemic as well as thromboembolic events. Before introducing OAT in patients with AF we must assess the risk of future bleeding episodes as OAT can lead to some life-threatening bleeding events. The most common risk score used for that purpose is HASBLED score. HAS-BLED score is valuable, proven tool in assessing future bleeding events in patients with AF. Nevertheless, it does not make the difference between dual and triple antithrombotic therapy which can be of great importance in preventing bleeding events.


Assuntos
Fibrilação Atrial , Intervenção Coronária Percutânea , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos
12.
Toxicol Lett ; 335: 91-97, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33157172

RESUMO

Nemopilema nomurai venom (NnV) is severely toxic to many organisms. However, the mechanism of its poisoning has not been properly understood yet. The present work demonstrates that zebrafish (Danio rerio) is an alternative vertebrate model for studying NnV jellyfish venom for the first time. In this model, NnV appears to cause severe hemorrhage and inflammation in cardiopulmonary regions of zebrafish. NnV also altered the swimming behavior of zebrafish accompanied by a significant downregulation of acetylcholinesterase (AChE) activity in brain tissues. Histopathological changes observed for various organs of D. rerio caused by NnV corresponded to an increase in lactate dehydrogenase (LDH) activity in tissues. NnV also significantly altered glutathione S-transferase (GST) activity in cardiopulmonary and brain tissues of D. rerio. SDS-PAGE revealed many protein bands of NnV of various sizes after silver staining. Taken together, these results indicate that Danio rerio can be a useful alternative animal model for jellyfish venom toxicology studies. Findings of the present study also suggest that Danio rerio could be used to develop an effective treatment strategy and discover the mechanism of action of jellyfish venom envenomation.


Assuntos
Venenos de Cnidários/toxicidade , Modelos Animais de Doenças , Hemorragia/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Cifozoários/química , Peixe-Zebra , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Venenos de Cnidários/isolamento & purificação , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Hemorragia/metabolismo , Hemorragia/patologia , Miocárdio/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/patologia
13.
N Engl J Med ; 383(22): 2117-2126, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33196155

RESUMO

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Bioprótese , Valva Mitral , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Doenças Cardiovasculares/epidemiologia , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Método Simples-Cego , Acidente Vascular Cerebral/prevenção & controle , Varfarina/efeitos adversos
14.
Int Heart J ; 61(6): 1204-1211, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33191346

RESUMO

The risk of thromboembolic events is significantly increased among patients with heart failure, even in those without atrial fibrillation. However, it is still unclear whether patients with heart failure and sinus rhythm can benefit from prophylactic anticoagulant therapy.This was a retrospective review of the pathophysiological mechanisms, epidemiological studies, and clinical trials on anticoagulation in patients with heart failure and sinus rhythm.Some subgroup analyses of clinical trials found that prophylactic anticoagulant therapy could reduce the incidence of stroke in patients with heart failure and sinus rhythm, and the risk of bleeding was significantly increased. Regarding the incidence of primary endpoint outcomes, all results from clinical trials were negative.Prophylactic anticoagulation did not improve the clinical outcome in patients with heart failure and sinus rhythm.


Assuntos
Anticoagulantes/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/sangue , Tromboembolia/epidemiologia , Tromboembolia/fisiopatologia
15.
Int Heart J ; 61(6): 1165-1173, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33191353

RESUMO

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA2DS2-VASc scores differed significantly between DOAC dosing regimens, with patients given an appropriate standard-dose being significantly younger (63.3 ± 9.4 versus 64.8 ± 9.5 versus 73.2 ± 6.8 years, P < 0.0001) and lower (2.1 ± 1.5 versus 2.4 ± 1.6 versus 3.4 ± 1.4, P < 0.0001) than those given an off-label under-dose or an appropriate low-dose. During the median 19.0-month follow-up period, the AF recurrence rate was similar between the appropriate standard-dose and off-label under-dose groups but relatively low in the appropriate low-dose group (42.5% versus 41.2% versus 35.4%, P = 0.08). Annualized rates of thromboembolic events, major bleeding, and death from any cause were 0.47%, 0.70%, and 0.23% in the off-label under-dose group, while those rates were 0.74%, 0.73%, and 0.65% in the appropriate standard-dose, and 1.58%, 2.12%, and 1.57% in the appropriate low-dose groups.In conclusion, the clinical adverse event rates for patients on an off-label under-dose DOAC regimen after ablation, predicated on careful patient evaluations, was not high as seen with that of patients on a standard DOAC dosing regimen.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter , Inibidores do Fator Xa/administração & dosagem , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Idoso , Fibrilação Atrial/complicações , Feminino , Hemorragia/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Uso Off-Label , Cuidados Pós-Operatórios , Recidiva , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia
18.
Curr Heart Fail Rep ; 17(6): 365-383, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33025463

RESUMO

PURPOSE OF REVIEW: Cardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation. RECENT FINDINGS: AF in cardio-oncology poses diagnostic and management challenges, also due to the number of anticancer drugs recently associated with AF onset/worsening. Oral targeted drugs can potentially interact with DOACs, with increased bleeding risk mainly due to pharmacokinetic DDIs. Moreover, the vast majority of oral anticancer agents cause QT prolongation with direct and indirect mechanisms, potentially resulting in the occurrence of torsade de pointes, especially in susceptible patients with COVID-19 receiving additional drugs with QT liability. Oncologists and cardiologists must be aware of the increased bleeding risk and arrhythmic susceptibility of patients with AF and cancer due to DDIs. High-risk individuals with COVID-19 should be prioritized to target preventive strategies, including optimal antithrombotic management, medication review, and stringent monitoring.


Assuntos
Antineoplásicos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Neoplasias/tratamento farmacológico , Tromboembolia/prevenção & controle , Fibrilação Atrial/complicações , Inibidores das Enzimas do Citocromo P-450/efeitos adversos , Sistema Enzimático do Citocromo P-450 , Interações Medicamentosas , Humanos , Síndrome do QT Longo/induzido quimicamente , Neoplasias/complicações , Tromboembolia/etiologia
19.
PLoS One ; 15(10): e0240489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035259

RESUMO

INTRODUCTION: Although the direct oral anticoagulant rivaroxaban is recommended for stroke prevention in patients with non-valvular atrial fibrillation based on Phase III clinical trials, there is still a need for additional safety data from everyday clinical practice. The ROSE study was initiated to collect further information on the safety and utilisation of rivaroxaban in a broader range of patient groups in routine clinical practice. METHODS AND RESULTS: The ROSE study was conducted in hospitals in England and Wales. Consenting adults with non-valvular atrial fibrillation newly started on rivaroxaban were eligible and followed up for 12 weeks. Data was derived through secondary use of medical records. The primary outcome was major bleeding within gastrointestinal, urogenital and intracranial sites. A total of 4846 patients were enrolled in the study September 2013 to January 2016, 965 of which were treated with rivaroxaban for non-valvular atrial fibrillation. The median age in the rivaroxaban non-valvular atrial fibrillation cohort was 76 years, 53.6% were male. The median HAS-BLED score was 2 and the median CHA2DS2-VASc score was 4. The risk of major bleeding within each of the primary sites of gastrointestinal, urogenital and intracranial during the 12 week observation period was low (0.2%; n = 2). The risk of major bleeding in all sites was 1.0% (n = 10) at a rate of 5.5 events per 100 patient years. CONCLUSION: In terms of the primary outcome risk of major bleeding within gastrointestinal, urogenital and intracranial sites during the 12 week observation period, the risk estimates in the non-valvular atrial fibrillation rivaroxaban user population were low (<1%), and consistent with risk estimated from clinical trial data and in routine clinical practice.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/epidemiologia , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Inibidores do Fator Xa/administração & dosagem , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Rivaroxabana/administração & dosagem , Atenção Secundária à Saúde , País de Gales/epidemiologia
20.
JAMA ; 324(16): 1640-1650, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107944

RESUMO

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention. Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice. Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019. Exposures: Ticagrelor vs clopidogrel. Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis. Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group. Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Clopidogrel/efeitos adversos , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Aspirina/administração & dosagem , Estudos de Casos e Controles , Causas de Morte , Clopidogrel/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Dispneia/induzido quimicamente , Feminino , Hemorragia/induzido quimicamente , Humanos , Isquemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Metanálise em Rede , Pontuação de Propensão , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Recidiva , República da Coreia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Ticagrelor/administração & dosagem , Estados Unidos
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