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1.
Medicine (Baltimore) ; 99(18): e19542, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32358343

RESUMEN

BACKGROUND: Data of non-vitamin K antagonist oral anticoagulants (NOACs) in current management of atrial fibrillation (AF) are predominantly derived from North American and European regions. However, the effects of NOACs for stroke prevention in Latin America remain unclear. Therefore, we aimed to compare the efficacy and safety of NOACs with warfarin in Latin American patients with AF. METHODS: The PubMed and Embase databases were systematically searched until July 12, 2019 for applicable randomized clinical trials. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS: Four trials involving 8943 Latin American patients were included in this meta-analysis. In anticoagulated patients with AF, Latin American patients had higher rates of stroke or systemic embolism and all-cause death compared with non-Latin American subjects. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism, major bleeding, intracranial bleeding, and any bleeding in Latin American patients. There were no significant differences in the risks of ischemic stroke, all-cause death, and gastrointestinal bleeding between Latin and non-Latin American groups. All the interactions between Latin and non-Latin American groups about efficacy and safety outcomes of NOACs compared with warfarin were non-significant (all Pinteraction > .05). CONCLUSIONS: Our meta-analysis suggested that the use of NOACs was at least non-inferior to warfarin use for stroke prevention in Latin American patients with AF.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Hispanoamericanos/estadística & datos numéricos , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico , Administración Oral , Adulto , Fibrilación Atrial/complicaciones , Fibrilación Atrial/etnología , Embolia/etnología , Embolia/prevención & control , Femenino , Hemorragia/inducido químicamente , Hemorragia/etnología , Humanos , América Latina , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/etnología , Resultado del Tratamiento
2.
Adv Exp Med Biol ; 1177: 101-131, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32246445

RESUMEN

Thrombosis, the localized clotting of blood that affects arterial or venous circulation, is one of the leading causes of death worldwide. Arterial thrombosis is commonly initiated by vascular endothelial injury, while venous thrombosis mainly stems from blood stasis. Despite these differences, platelet adhesion, activation and aggregation, and fibrin formation as a result of coagulation constitute the fundamental processes of thrombus formation. Antithrombotic drugs permitted on the clinical currently can dramatically reduce major adverse cardiovascular events; however, they can also increase the bleeding risk. Discovery of antithrombotic drugs that can effectively prevent thrombosis while sparing bleeding side effects remains unmet medical need. In this chapter, we provide an overview on the pathophysiology of thrombosis, followed by introduction of each class of antithrombotic drugs including their pharmacology, clinical applications and limitations. Practical challenges and future perspectives of antithrombotic drugs are discussed in the last part of this chapter.


Asunto(s)
Fibrinolíticos/farmacología , Trombosis/prevención & control , Coagulación Sanguínea/efectos de los fármacos , Hemorragia/inducido químicamente , Humanos , Adhesividad Plaquetaria/efectos de los fármacos
3.
N Engl J Med ; 382(18): 1696-1707, 2020 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-32223116

RESUMEN

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).


Asunto(s)
Anticoagulantes/uso terapéutico , Clopidogrel/uso terapéutico , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Clopidogrel/efectos adversos , Quimioterapia Combinada , Hemorragia/epidemiología , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos
4.
N Engl J Med ; 382(17): 1599-1607, 2020 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-32223112

RESUMEN

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use. METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding. RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).


Asunto(s)
Anticoagulantes/administración & dosificación , Dalteparina/administración & dosificación , Hemorragia/inducido químicamente , Neoplasias/complicaciones , Pirazoles/administración & dosificación , Piridonas/administración & dosificación , Prevención Secundaria/métodos , Tromboembolia Venosa/prevención & control , Administración Oral , Anciano , Anticoagulantes/efectos adversos , Dalteparina/efectos adversos , Femenino , Hemorragia/epidemiología , Humanos , Incidencia , Inyecciones Subcutáneas , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Modelos de Riesgos Proporcionales , Embolia Pulmonar/prevención & control , Pirazoles/efectos adversos , Piridonas/efectos adversos , Método Simple Ciego , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Trombosis de la Vena/prevención & control
5.
Rev Med Suisse ; 16(684): 459-462, 2020 Mar 04.
Artículo en Francés | MEDLINE | ID: mdl-32134226

RESUMEN

Low-dose aspirin in primary prevention of cardiovascular disease is still debated. Recent clinical trials of aspirin vs placebo reported an unfavourable risk-benefit ratio with an increase in major bleedings without reduction on the occurrence of non-fatal cardiovascular events. These studies also highlight that current cardiovascular risk calculators overestimate cardiovascular risk, which is probably related to the improvement in the management of cardiovascular risk factors over the last decades. In accordance with European cardiovascular prevention recommendations, aspirin should not be prescribed for the primary prevention of cardiovascular disease.


Asunto(s)
Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Prevención Primaria/métodos , Prevención Primaria/tendencias , Aspirina/administración & dosificación , Hemorragia/inducido químicamente , Humanos , Medición de Riesgo
6.
Ther Adv Cardiovasc Dis ; 14: 1753944720911329, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32168991

RESUMEN

BACKGROUND: The objective of this review is to provide a practical update on endpoint selection for noninferiority (NI) studies in percutaneous coronary intervention studies. METHODS: A PubMed search was conducted for predefined terms to explore the use of NI designs and intrapatient comparisons to determine their current importance. Sample size calculations for the most frequently used endpoints with NI hypotheses were done to increase statistical awareness. RESULTS: Reported NI trials, with the most frequently chosen clinical endpoint of major adverse cardiac events (MACE), had NI margins ranging from 1.66% to 5.00%, resulting in patient populations of 400-1500 per treatment group. Clinical study endpoints comprising of MACE complemented with rates of bleeding complications and stent thrombosis (ST) are suggested to conduct a statistically and clinically meaningful NI trial. Study designs with surrogate endpoints amenable to intrapatient randomizations, are a very attractive option to reduce the number of necessary patients by about half. Comparative clinical endpoint studies with MACE and ST/bleeding rates to study a shortened dual antiplatelet therapy (DAPT) in coronary stent trials are feasible, whereas ST as the sole primary endpoint is not useful. CONCLUSIONS: Expanded composite clinical endpoints (MACE complemented by ST and bleeding rates and intrapatient randomization for selected surrogate endpoints) may be suitable tools to meet future needs in device approval, recertification and reimbursement.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Determinación de Punto Final , Estudios de Equivalencia como Asunto , Intervención Coronaria Percutánea , Proyectos de Investigación , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Trombosis Coronaria , Quimioterapia Combinada , Hemorragia/inducido químicamente , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Factores de Riesgo , Tamaño de la Muestra , Stents , Factores de Tiempo , Resultado del Tratamiento
7.
Expert Rev Cardiovasc Ther ; 18(1): 17-24, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32003297

RESUMEN

Introduction: Platelets play a pivotal role in the occurrence of recurrent ischemic events in coronary artery disease patients who are treated with drug-eluting stents and are on dual antiplatelet therapy (DAPT).Areas covered: High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy is a strong predictor of post-stenting ischemic event occurrences. However, uniform use of potent P2Y12 receptors blockers to overcome HPR is associated with elevated bleeding risk. Selective de-escalation of P2Y12 receptor blocker therapy based on PFT in patients with acute coronary syndrome treated with stenting has been shown to be associated with a similar risk of ischemic event occurrence but with a reduced risk of bleeding. This review aims to discuss the role of PFT in guiding DAPT in patients treated with DES. We searched electronic databases from January 2000 to December 2019 for literatures evaluating the role of platelet function assessment after drug eluting stents.Expert opinion: Platelet function guided therapy improves patient outcomes by lessening bleeding and limiting the overuse of highly potent P2Y12 inhibitors. Interest in this area of de-escalation of therapy will likely grow as the consequences of bleeding are better recognized and the cost of healthcare gains greater focus.


Asunto(s)
Plaquetas/metabolismo , Stents Liberadores de Fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Síndrome Coronario Agudo/terapia , Clopidogrel/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Quimioterapia Combinada , Stents Liberadores de Fármacos/efectos adversos , Hemorragia/inducido químicamente , Humanos , Pruebas de Función Plaquetaria , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación
8.
Medicine (Baltimore) ; 99(5): e19000, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000440

RESUMEN

BACKGROUND: Patients with cancer are of a high level risk of venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is recommended as the normal treatment for cancer-associated venous thrombosis. Recently, some studies suggest that patients with cancer-associated venous thrombosis can get a good efficacy and safety profile from treating with direct oral anticoagulants (DOACs) compared with other anticoagulants. However, when it comes to the efficacy of DAOCs in preventing VTE in patient with cancer, the data are limited. Thus, we performed such a meta-analysis to determine the efficacy and safety of DOACs in preventing VTE in patient with cancer compared with LMWHs. METHODS: Medline/PubMed and CENTRAL (The Cochrane Central Register of Controlled Trials) were systematically searched for relevant studies. For each trial, data on VTE, major bleeding, or bleeding were extracted by 2 reviewers independently. Pooled risk ratios (RRs) were calculated by using Review Manager 5.3 software and the significance was determined by the Z test. RESULTS: A total of 6 studies with 7185 patients were included in our meta-analysis. DOACs (RR = 0.55, 95% confidence interval [95%CI]: 0.34-0.90, I = 31%) had a similar prevention effect of VTE to LMWH (RR = 0.59, 95% CI: 0.37-0.95, I = 59%). DOACs (RR = 1.52, 95% CI: 0.99-2.33, I = 0%) yielded a similar bleeding occurrence rate compared with LMWH (RR = 1.35, 95% CI: 1.07-1.70, I = 35%). DOACs (RR = 1.95, 95% CI: 0.88-4.30, I = 0%) showed a sight higher major bleeding occurrence rate than LMWH (RR = 1.38, 95% CI: 0.88-2.14, I = 0%). CONCLUSION: DOACs show comparable efficacy to LMWH in cancer patients without VTE with a slightly higher major bleeding occurrence rate. DOACs are inclined to be an alternative thromboprophylaxis strategy in cancer patients as they have superiorities compared to traditional anticoagulation agents. Further studies are still demanded as exiting relevant researches are limited.


Asunto(s)
Anticoagulantes/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Neoplasias/complicaciones , Tromboembolia Venosa/prevención & control , Administración Oral , Hemorragia/inducido químicamente , Humanos
9.
N Engl J Med ; 382(13): 1208-1218, 2020 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-32050061

RESUMEN

BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Inmunosupresores/administración & dosificación , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Polímeros , Sirolimus/análogos & derivados , Trombosis Coronaria/etiología , Trombosis Coronaria/mortalidad , Quimioterapia Combinada , Stents Liberadores de Fármacos/efectos adversos , Cardiopatías/mortalidad , Hemorragia/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Inhibidores de Agregación Plaquetaria/efectos adversos , Diseño de Prótesis , Método Simple Ciego , Sirolimus/administración & dosificación
10.
Monaldi Arch Chest Dis ; 90(1)2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-32088948

RESUMEN

Diffuse alveolar haemorrhage (DAH) is characterised by diffuse pulmonary opacities, respiratory failure, a falling haemoglobin level along with presence of hemosiderin-laden macrophages on bronchoalveolar lavage (BAL). Finding the underlying aetiology of DAH can be challenging but of importance as the treatment and prognosis are largely determined by it. We report a case of DAH with underlying cocaine abuse, a rare cause for the same.


Asunto(s)
Trastornos Relacionados con Cocaína/diagnóstico , Hemorragia/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Humanos , Pronóstico
11.
Expert Opin Drug Metab Toxicol ; 16(1): 1-9, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914334

RESUMEN

Background: Warfarin acts in heart valve replacement patients to minimize thromboembolic complications. We investigated whether patients can be distinguished based on their genotypes to efficiently and safely administer warfarin therapy after heart valve replacements.Research design and methods: A retrospective analysis was conducted in patients with warfarin therapy who underwent elective heart valve replacements between January 2013 and September 2018. The patients were divided into normal, sensitive, and highly sensitive bins based on their CYP2C9 and VKORC1 genotypes. The primary endpoints were over-anticoagulation and overt bleeding.Results: 375 patients were enrolled, with 65 classified as normal, 281 as sensitive, and 29 as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent more time on over-anticoagulation in the first 28 (P < 0.001) and 90 (P = 0.001) days; experienced more frequent bleeding events in the first 28 days (P = 0.029; OR, 2.18; 95% CI, 1.15-4.13); required lower warfarin doses to obtain stable INR (P < 0.001); had higher warfarin sensitivity indices (P < 0.001).Conclusion: Predicting evidence have been obtained with CYP2C9 and VKORC1 genotypes in identifying heart valve replacement patients with higher efficient sensitivity and with a higher risk of bleeding and over-anticoagulation.


Asunto(s)
Anticoagulantes/administración & dosificación , Citocromo P-450 CYP2C9/genética , Hemorragia/inducido químicamente , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Adulto , Anciano , Anticoagulantes/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Genotipo , Implantación de Prótesis de Válvulas Cardíacas/métodos , Hemorragia/epidemiología , Hemorragia/genética , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia/prevención & control , Warfarina/efectos adversos
12.
JAMA ; 323(2): 130-139, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31935028

RESUMEN

Importance: The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa. Objective: To compare different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty. Design, Setting, and Participants: Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019. Interventions: Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography. Main Outcomes and Measures: The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively. Results: Of 813 randomized participants (mean [SD] age, 66.5 years [8.2 years]; body mass index, 32.7 [5.7]; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, -1.2% to ∞) at the 0.6-mg/kg dose; 9.9% (95% CI, -0.9% to ∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, -2.6 to ∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, -8.9% to ∞) and -3.6% (95% CI, -15.5% to ∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban. Conclusions and Relevance: Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis. Trial Registration: ClinicalTrials.gov Identifier: NCT03276143.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticoagulantes/administración & dosificación , Artroplastia de Reemplazo de Rodilla , Inhibidores del Factor Xa/administración & dosificación , Hemorragia/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Tromboembolia Venosa/prevención & control , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticoagulantes/efectos adversos , Relación Dosis-Respuesta a Droga , Enoxaparina/administración & dosificación , Enoxaparina/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Embolia Pulmonar/prevención & control , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Piridonas/administración & dosificación , Piridonas/efectos adversos , Método Simple Ciego , Trombosis de la Vena/prevención & control
14.
Niger J Clin Pract ; 23(1): 120-122, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31929218

RESUMEN

We present a very rare case of Sevoflurane Induced Diffuse Alveolar Haemorrhage in a young male patient with a closed tibial fracture after direct trauma to the right cruris. The patient was operated for tibial fracture, but diffuse alveolar haemorrhage developed after sevoflurane inhalation in the postoperative period following general anesthesia. Diffuse alveolar haemorrhage (DAH) is associated with inhalation injury from halogenated gases and reported as a unique entity in the literature that practicing clinicians should be aware of and consider in post-operative cases of acute respiratory distress. As DAH usually presents with symptoms the presence of hemoptysis, anemia, dyspnoea and radiological alveolar infiltrates, rapid detection of the aetiology and initiation of cause-directed treatment are of great importance on survival.


Asunto(s)
Anestésicos por Inhalación/efectos adversos , Hemoptisis/inducido químicamente , Hemorragia/inducido químicamente , Procedimientos Ortopédicos/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Alveolos Pulmonares/diagnóstico por imagen , Sevoflurano/farmacología , Fracturas de la Tibia/cirugía , Adulto , Anestesia General , Broncoscopía , Hemoptisis/terapia , Humanos , Masculino , Complicaciones Posoperatorias/terapia , Periodo Posoperatorio , Alveolos Pulmonares/patología , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento
15.
Angiology ; 71(2): 131-138, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31578072

RESUMEN

Patients with autoimmune disorders are at an increased risk of venous thromboembolism (VTE), but this association has not been consistently evaluated. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to compare the rates of VTE recurrences, major bleeding, and death during the course of anticoagulation, according to the presence or absence of autoimmune disorders. Of 71 625 patients with VTE recruited in February 2018, 1800 (2.5%) had autoimmune disorders. Median duration of anticoagulant therapy was slightly longer in patients with autoimmune disorders (median, 190 vs 182 days; P = .001). On multivariable analysis, patients with autoimmune disorders had a similar risk of VTE recurrences (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.68-1.27) or major bleeding (HR: 1.07; 95% CI: 0.82-1.40) and a lower risk to die (HR: 0.66; 95% CI: 0.54-0.81) than those without autoimmune disorders. Patients with giant cell arteritis had the highest rates of major bleeding (8.6 events per 100 patient-years) and the lowest rate of recurrences (zero). In other subgroups, the rates of both events were more balanced. During anticoagulation, patients with or without autoimmune disorders had similar rates of VTE recurrences or major bleeding. However, there were some differences between subgroups of patients with autoimmune disorders.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Tromboembolia Venosa/etiología , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Bases de Datos Factuales , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Sistema de Registros , Medición de Riesgo , España , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología
16.
Toxicol Lett ; 319: 250-255, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31778774

RESUMEN

The effect of thalidomide on mandibular development is unclear. In this study, thalidomide was delivered to pregnant rabbits from the 8th to 14th day of gestation. Then, embryos were harvested for examination on the 16th day (GD16), 20th day (GD20) and 24th day (GD24) of gestation. The results showed obvious hemorrhage and hematoma on one side of the craniofacial region in 50 % of the thalidomide-treated embryos and obvious hemorrhage and hematoma on both sides of the craniofacial region in 50 % of the thalidomide-treated embryos at GD16. Histological examination showed soft tissues and mandible defects on the affected side of the maxillofacial region. The expression of Vegf-α, Ki67 and Sox9 on the affected side was significantly down-regulated in comparison to their expression on the unaffected side at GD20. There was also an obvious defect in the affected mandible, and the density of the skull and mandible was decreased compared to the unaffected side or the control group at GD24. These findings demonstrated that thalidomide may lead to hemorrhage and hematoma in the craniofacial region by inhibiting angiogenesis, resulting in the abnormal development of cranial neural crest cells that are involved in the normal development of the mandible in rabbits.


Asunto(s)
Anomalías Craneofaciales/inducido químicamente , Anomalías Craneofaciales/patología , Hemorragia/inducido químicamente , Hemorragia/patología , Mandíbula/patología , Neovascularización Fisiológica/efectos de los fármacos , Teratógenos/toxicidad , Talidomida/toxicidad , Animales , Regulación hacia Abajo/efectos de los fármacos , Femenino , Mandíbula/anomalías , Anomalías Maxilofaciales/inducido químicamente , Anomalías Maxilofaciales/patología , Cresta Neural/patología , Embarazo , Conejos , Cráneo/anomalías
17.
Expert Opin Drug Metab Toxicol ; 16(1): 31-44, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31795773

RESUMEN

Introduction: This is a review of the drug interactions (DIs) between newer antidepressants and oral anticoagulants (OACs): vitamin K antagonists (VKAs) and direct-acting OACs (DOACs).Areas covered: Articles were obtained from PubMed searches performed for each of the newer antidepressants and oral anticoagulants. The basic pharmacokinetic and pharmacodynamic mechanisms for DIs with these drugs were summarized. Some newer antidepressants are inhibitors of a number of cytochrome P450 (CYP) isoforms and many antidepressants appear to have potential to impair serotonin platelet function and increase bleeding risk.Expert opinion: Clinicians should not forget that the DIs between newer antidepressants and VKAs can be potentially lethal. Among SSRIs, fluoxetine and fluvoxamine appear to be associated with the highest DI risk with warfarin, the most commonly prescribed VKA worldwide. Case reports featuring duloxetine, mirtazapine and trazadone suggested potential for interaction with warfarin. As CYP3A4 is an important metabolic pathway for all DOACs except dabigatran, it appears reasonable to recommend avoiding the co-prescription of fluoxetine and fluvoxamine (weak to moderate CYP3A4 inhibitors) and St John's wort (CYP3A4 inducer). Many package inserts for the newer antidepressants include a warning regarding an increased risk of bleeding events with concomitant use of these agents with OACs.


Asunto(s)
Anticoagulantes/administración & dosificación , Antidepresivos/administración & dosificación , Interacciones Farmacológicas , Administración Oral , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Antidepresivos/efectos adversos , Antidepresivos/farmacología , Inhibidores Enzimáticos del Citocromo P-450/administración & dosificación , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Hemorragia/inducido químicamente , Humanos , Vitamina K/antagonistas & inhibidores , Warfarina/administración & dosificación , Warfarina/efectos adversos , Warfarina/farmacocinética
18.
World Neurosurg ; 133: e385-e390, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31521761

RESUMEN

BACKGROUND: Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. METHODS: Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. RESULTS: Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. CONCLUSIONS: An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.


Asunto(s)
Aspirina/uso terapéutico , Traumatismos Cerebrovasculares/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Heridas no Penetrantes/tratamiento farmacológico , Adolescente , Adulto , Anciano , Aneurisma Disecante/etiología , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Aspirina/efectos adversos , Traumatismos de las Arterias Carótidas/tratamiento farmacológico , Arteria Carótida Interna , Traumatismos Cerebrovasculares/complicaciones , Traumatismos Cerebrovasculares/epidemiología , Manejo de la Enfermedad , Evaluación de Medicamentos , Femenino , Hemorragia/inducido químicamente , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Arteria Vertebral/lesiones , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/epidemiología , Adulto Joven
19.
N Engl J Med ; 382(2): 120-129, 2020 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-31733180

RESUMEN

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).


Asunto(s)
Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Clopidogrel/efectos adversos , Quimioterapia Combinada , Inhibidores del Factor Xa/efectos adversos , Femenino , Prótesis Valvulares Cardíacas , Hemorragia/inducido químicamente , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/efectos adversos , Tromboembolia/mortalidad
20.
N Engl J Med ; 382(2): 130-139, 2020 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-31733182

RESUMEN

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).


Asunto(s)
Válvula Aórtica/fisiopatología , Aspirina/farmacología , Clopidogrel/farmacología , Inhibidores del Factor Xa/farmacología , Prótesis Valvulares Cardíacas , Inhibidores de Agregación Plaquetaria/farmacología , Rivaroxabán/farmacología , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Válvula Aórtica/efectos de los fármacos , Válvula Aórtica/patología , Aspirina/efectos adversos , Aspirina/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Quimioterapia Combinada , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Femenino , Tomografía Computarizada Cuatridimensional , Hemorragia/inducido químicamente , Humanos , Análisis de Intención de Tratar , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Tromboembolia/etiología , Tromboembolia/mortalidad
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