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1.
Angiology ; 71(1): 27-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31533437

RESUMO

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.


Assuntos
Anticoagulantes/administração & dosagem , Infarto do Miocárdio/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Esquema de Medicação , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/mortalidade , Meta-Análise em Rede , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Pan Afr Med J ; 33: 160, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31565122

RESUMO

Intra-alveolar bleeding is a rare and severe medical emergency due to numerous causes. We report the clinical case of a patient who could contribute to extend the literature on this subject. The study included a 62-year old man, with a history of a trial fibrillation, under anti-vitamins K antagonist admitted with dyspnoea of sudden onset associated with haemoptysis and practising self-medication using non-steroidal anti-inflammatory drugs. X-rays and chest scan showed diffuse bilateral alveolar opacities. Haemostatic screening tests on admission showed non-coagulable INR. The diagnosis of intra-alveolar bleeding was clinically and radiologically suspected and then confirmed by bronchial endoscopy with broncho-alveolar lavage (BAL) which detected uniformly hemorrhagic liquid. Previous studies of similar complications occurring after anti-vitamins K antagonists assumption are rare. In conclusion, it seems very important to emphasize the interest of strict and optimal clinico-biological monitoring of patients treated in anti-vitamins K antagonists to avoid an overdose which could contribute to a life-threatening severe haemorrhagic event.


Assuntos
Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Alvéolos Pulmonares/patologia , Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Dispneia/induzido quimicamente , Hemoptise/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina K/antagonistas & inibidores
4.
N Engl J Med ; 381(16): 1524-1534, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31475799

RESUMO

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Trombose Coronária/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
5.
N Engl J Med ; 381(14): 1309-1320, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31475798

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Resultado do Tratamento
6.
JAMA ; 322(9): 834-842, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479138

RESUMO

Importance: The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective: To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants: The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions: In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures: The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results: Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance: Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01006733.


Assuntos
Anticoagulantes/administração & dosagem , Artroplastia de Quadril , Artroplastia do Joelho , Coeficiente Internacional Normatizado , Tromboembolia Venosa/prevenção & controle , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Tromboembolia Venosa/mortalidade , Varfarina/efeitos adversos
7.
N Engl J Med ; 381(17): 1621-1631, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31479209

RESUMO

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).


Assuntos
Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Método Simples-Cego , Stents , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
8.
Lancet ; 394(10204): 1169-1180, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31484629

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. FUNDING: AstraZeneca.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Estenose Coronária/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
9.
N Engl J Med ; 381(21): 2032-2042, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31556978

RESUMO

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).


Assuntos
Aspirina/uso terapêutico , Doença das Coronárias/terapia , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doença das Coronárias/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Ticagrelor/efeitos adversos
10.
Expert Rev Cardiovasc Ther ; 17(9): 633-643, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382819

RESUMO

Introduction: While the clinical merits of aspirin in secondary cardiovascular disease (CVD) prevention remain undisputed, its role in primary prevention is controversial. Recently, three trials of primary prevention reported neutral net benefit results or evidence of harm for aspirin in patients with no overt CVD. Areas covered: This article aims to inform clinical practitioners by appraising the current body of evidence on the use of aspirin for primary CVD prevention, ranging from general pharmacology to clinical outcomes and future directions. Expert opinion: Based on meta-analyses incorporating latest trials in the field of primary prevention, the modest reduction in ischemic events with aspirin, if any, is offset by a modest increase in nonfatal bleeding. Improved control of CVD risk factors and broader use of statins may have reduced the thrombotic complications of atherosclerosis, thus limiting the opportunity for aspirin to prevent clinical CVD events in the contemporary era. As such, decision-making about aspirin for primary prevention is challenging even when selected patients are considered and involves careful weighing of risks and benefits. Ongoing investigations conducted in patients with cancer could rapidly modify the current perception of the unfavorable benefit-risk ratio of aspirin in patients with no overt CVD.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Aterosclerose/tratamento farmacológico , Tomada de Decisões , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Seleção de Pacientes , Prevenção Primária/métodos
11.
Ther Adv Cardiovasc Dis ; 13: 1753944719863641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364490

RESUMO

BACKGROUND: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS: A post hoc exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no versus yes)]. CONCLUSIONS: The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Isquemia Encefálica/mortalidade , Tomada de Decisão Clínica , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
12.
Vasc Health Risk Manag ; 15: 175-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417269

RESUMO

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. Compared with the general population, cancer patients with VTE have higher rates of both VTE recurrence and bleeding. While low molecular weight heparin (LMWH) has been the mainstay of treatment for cancer-associated VTE for over a decade, direct oral anticoagulants (DOACs) have recently emerged as a new therapeutic option due to their ease of administration and because they do not require laboratory monitoring. Several large randomized clinical trials have been performed or are ongoing at the time of writing, comparing DOACs with LMWH in this population. Three of these trials have thus far been published and suggest that DOACs are a reasonable alternative to LMWH for management of cancer-associated VTE. Despite the advantages offered by DOACs, these agents may not be appropriate for certain patient groups owing to increased risk of bleeding, organ compromise, extremes of weight, and other issues. Finally, data are emerging suggesting that DOACs may be useful for primary thromboprophylaxis in cancer patients in conjunction with validated risk assessment scores. In this evidence-based review, data for the use of DOACs to treat cancer-associated VTE will be examined, focusing on efficacy, safety, and timing of treatment. Guidance on choosing the optimal anticoagulant for a given patient is also offered.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade
13.
Cancer Treat Res ; 179: 103-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317483

RESUMO

The management of cancer-associated thrombosis (CAT) is complex, and treatment strategies have been evolving over the past 15 years. It is well recognized that oral vitamin K antagonists are difficult to use in cancer patients, with higher rates of treatment failure and bleeding complications than in non-cancer patients. Low-molecular-weight-heparin (LMWH) became the widely accepted standard of care for treatment of cancer-associated thrombosis, following the CLOT study comparing dalteparin with warfarin in 2003. LMWH remains widely used for the treatment of CAT. However, in the past two years, several studies have served to validate direct oral anticoagulants as a safe and effective alternative to LMWH. Two randomized clinical trials comparing edoxaban and rivaroxaban with dalteparin, and several retrospective studies have shown the efficacy of edoxaban and rivaroxaban for the treatment of CAT. However, there is an evidence of increased bleeding with the DOACs, particularly gastrointestinal or urinary tract bleeding in patients with lesions within the gastrointestinal or urinary tracts. This chapter discusses the ongoing development of optimal treatment strategies for cancer-associated thrombosis.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
14.
Cancer Treat Res ; 179: 191-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317489

RESUMO

Cancer can be associated with several distinct coagulation defects which can lead to bleeding complications. The primary hyperfibrinolytic syndrome associated with acute promyelocytic leukemia has been well recognized and is one of the most severe bleeding disorders. Acquired hemophilia, while rare and not only seen in the oncology setting, can be triggered by a malignancy and must be promptly recognized in order to prevent catastrophic hemorrhage. Other, less serious coagulopathic states have been linked to cancer, including acquired von Willebrand disease. Finally, several anti-neoplastic drugs can alter hemostasis and increase the risk of bleeding. A good understanding of this field can help mitigate the risk of complications in the cancer patient.


Assuntos
Antineoplásicos/efeitos adversos , Transtornos da Coagulação Sanguínea/etiologia , Neoplasias/complicações , Antineoplásicos/uso terapêutico , Transtornos da Coagulação Sanguínea/induzido quimicamente , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Hemostasia/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico
15.
Arch Cardiovasc Dis ; 112(8-9): 469-484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31262635

RESUMO

BACKGROUND: Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited. AIM: To compare ischaemic and bleeding risks across the major c-DESs used in France. METHODS: French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics. RESULTS: A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 [95% confidence interval 0.68-1.07] and 1.04 [95% confidence interval 0.98-1.10] compared with XIENCE® used as the reference) and when each outcome was considered separately. CONCLUSIONS: In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.


Assuntos
Doença da Artéria Coronariana/terapia , Trombose Coronária/epidemiologia , Stents Farmacológicos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Bases de Dados Factuais , Feminino , França/epidemiologia , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Desenho de Prótese , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Anticancer Res ; 39(7): 3871-3878, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262915

RESUMO

BACKGROUND: Lenvatinib has become an important treatment option for advanced thyroid cancer. Fistula and tumor-related bleeding are life-threatening adverse effects that are triggered by tumor shrinkage. The aim of this study was to evaluate basic parameters, such as time and tumor shrinkage level, and analyze patient characteristics that might be related to onset of complications. PATIENTS AND METHODS: A retrospective study of 16 patients who received lenvatinib for thyroid cancer treatment was performed. RESULTS: Fistula was observed in two patients (12.5%), while tumor-related bleeding was observed in one (6.3%). Complications were found to appear at 10.4 weeks from initiation and with tumor decrease of 19.2%. Risk factors for complications were identified as anaplastic histological type, tumor invasion, and leukocytopenia induced by lenvatinib. CONCLUSION: Individual dose adjustment is needed with respect to these features in order to manage severe adverse effects induced by lenvatinib.


Assuntos
Antineoplásicos/efeitos adversos , Fístula/induzido quimicamente , Hemorragia/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/patologia
17.
Artigo em Chinês | MEDLINE | ID: mdl-31256533

RESUMO

Objective: To report a case of rat poison with multiple hemorrhage after trauma. Methods: The clinical data of a case of rodenticide poisoning with hemorrhage as the first symptom admitted to a third-class a hospital in July 2018 were analyzed and summarized. Results: This patient is a rodent drug poisoning patient with hemorrhage as the first symptom.The disease was diagnosed as bromohamelin and bromadiolone poisoning through the analysis of poison detection because the rodent drug was taken in the market and the history of taking poison was concealed. The patient was given active comprehensive treatment of vitamin K1 and other drugs for clinical cure. Conclusion: For patients with clinically unexplained hemorrhage, the possibility of rodenticide poisoning should be considered and the toxicant detection should be improved actively.


Assuntos
Hemorragia , Venenos , Animais , Hemorragia/induzido quimicamente , Humanos , Ratos
18.
High Blood Press Cardiovasc Prev ; 26(4): 283-291, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31280451

RESUMO

INTRODUCTION: The role of aspirin as a means of primary prevention remains controversial. AIM: We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention. METHODS: Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001). CONCLUSIONS: Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.


Assuntos
Aspirina/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Prevenção Primária/métodos , Aspirina/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Tomada de Decisão Clínica , Hemorragia/induzido quimicamente , Humanos , Incidência , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Expert Rev Clin Pharmacol ; 12(8): 771-780, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31269825

RESUMO

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.


Assuntos
Aterosclerose/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Animais , Aspirina/administração & dosagem , Aterosclerose/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/induzido quimicamente , Humanos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacologia , Prevenção Secundária/métodos
20.
Clin Adv Hematol Oncol ; 17(4): 223-233, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31188814

RESUMO

Mantle cell lymphoma (MCL) is a heterogeneous and uncommon non-Hodgkin lymphoma that affects predominantly older patients and often is associated with an aggressive clinical course. MCL relies upon B-cell receptor signaling through Bruton tyrosine kinase (BTK); therefore, the development of the BTK inhibitors ibrutinib and acalabrutinib represents a therapeutic breakthrough. In this review, we provide a summary of the efficacy and safety data from the landmark trials of single-agent ibrutinib and acalabrutinib that led to US Food and Drug Administration approval of these agents for patients with relapsed or refractory MCL. Toxicities of interest observed with ibrutinib include bleeding, atrial fibrillation, and increased risk for infection. The selectivity of acalabrutinib for BTK is greater than that of ibrutinib, which mitigates the risk for certain off-target toxicities, including atrial fibrillation; however, these toxicities, along with frequent headaches, still occur. Ongoing clinical trials are investigating both alternate BTK inhibitors and BTK inhibitors in combination with chemo-immunotherapy or other targeted agents in an effort to enhance the depth and duration of response. Trials to evaluate the use of these agents in the frontline setting are emerging and are likely to build upon the success of BTK inhibitors in patients with MCL.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Antígenos CD20/efeitos dos fármacos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Ensaios Clínicos como Assunto , Previsões , Neoplasias Gastrointestinais/induzido quimicamente , Hemorragia/induzido quimicamente , Humanos , Fatores Imunológicos/administração & dosagem , Linfocitose/induzido quimicamente , Linfoma de Célula do Manto/enzimologia , Terapia de Alvo Molecular/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Pirazinas/efeitos adversos , Pirazinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Terapia de Salvação
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