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1.
JAMA ; 324(15): 1522-1531, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079154

RESUMO

Importance: Heart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency. Objective: To evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF. Design, Setting, and Participants: CAPACITY HFpEF was a randomized, double-blind, placebo-controlled, phase 2 trial. Fifty-nine sites enrolled 196 patients with heart failure and an ejection fraction of at least 40%, impaired peak rate of oxygen consumption (peak V̇o2), and at least 2 conditions associated with nitric oxide deficiency (diabetes, hypertension, obesity, or advanced age). The trial randomized patients to 1 of 3 praliciguat dose groups or a placebo group, but was refocused early to a comparison of the 40-mg praliciguat dose vs placebo. Participants were enrolled from November 15, 2017, to April 30, 2019, with final follow-up on August 19, 2019. Interventions: Patients were randomized to receive 12 weeks of treatment with 40 mg of praliciguat daily (n = 91) or placebo (n = 90). Main Outcomes and Measures: The primary efficacy end point was the change from baseline in peak V̇o2 in patients who completed at least 8 weeks of assigned dosing. Secondary end points included the change from baseline in 6-minute walk test distance and in ventilatory efficiency (ventilation/carbon dioxide production slope). The primary adverse event end point was the incidence of treatment-emergent adverse events (TEAEs). Results: Among 181 patients (mean [SD] age, 70 [9] years; 75 [41%] women), 155 (86%) completed the trial. In the placebo (n = 78) and praliciguat (n = 65) groups, changes in peak V̇o2 were 0.04 mL/kg/min (95% CI, -0.49 to 0.56) and -0.26 mL/kg/min (95% CI, -0.83 to 0.31), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -0.30 mL/kg/min ([95% CI, -0.95 to 0.35]; P = .37). None of the 3 prespecified secondary end points were statistically significant. In the placebo and praliciguat groups, changes in 6-minute walk test distance were 58.1 m (95% CI, 26.1-90.1) and 41.4 m (95% CI, 8.2-74.5), respectively; the placebo-adjusted least-squares between-group difference in mean change from baseline was -16.7 m (95% CI, -47.4 to 13.9). In the placebo and praliciguat groups, the placebo-adjusted least-squares between-group difference in mean change in ventilation/carbon dioxide production slope was -0.3 (95% CI, -1.6 to 1.0). There were more dizziness (9.9% vs 1.1%), hypotension (8.8% vs 0%), and headache (11% vs 6.7%) TEAEs with praliciguat compared with placebo. The frequency of serious TEAEs was similar between the groups (10% in the praliciguat group and 11% in the placebo group). Conclusions and Relevance: Among patients with HFpEF, the soluble guanylate cyclase stimulator praliciguat, compared with placebo, did not significantly improve peak V̇o2 from baseline to week 12. These findings do not support the use of praliciguat in patients with HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT03254485.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Oxigênio/metabolismo , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Administração Oral , Idoso , Método Duplo-Cego , Feminino , Guanilato Ciclase/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Pirimidinas/efeitos adversos , Pirimidinas/farmacologia , Volume Sistólico , Falha de Tratamento , Teste de Caminhada
2.
N Engl J Med ; 383(11): 1040-1049, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32905676

RESUMO

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Antagonistas de Receptores de Andrógenos/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Fadiga/induzido quimicamente , Fraturas Ósseas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Pirazóis/efeitos adversos
3.
J Stroke Cerebrovasc Dis ; 29(9): 105034, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807446

RESUMO

BACKGROUND: Data on independent risk factors for stroke recurrence in Japanese patients with nonvalvular atrial fibrillation are limited. METHODS: We performed a subgroup analysis of a postmarketing surveillance study of apixaban (STroke prevention ANticoagulant Drug Apixaban Real-world Data study) in Japanese patients with nonvalvular atrial fibrillation receiving oral apixaban (5 mg/2.5 mg twice daily) in routine clinical practice. Patients were categorized into primary and secondary prevention groups based on the absence or presence of a history of ischemic stroke/transient ischemic attack, respectively. RESULTS: Patients in the secondary prevention group (1101 of 6306 patients [17.5%] analyzed; mean observation period, 15.7 months) had a higher risk of ischemic stroke or hemorrhage than those in the primary prevention group. The incidence rates of major (3.92%/year vs 2.06%/year), intracranial (1.87%/year vs 0.55%/year), and cerebral (1.14%/year vs 0.37%/year) hemorrhage and effectiveness outcomes (ischemic stroke/systemic embolism/transient ischemic attack, 3.25%/year vs 0.57%/year) were significantly higher (all P < 0.001) in the secondary prevention group than in the primary prevention group. Multivariate analysis identified no independent risk factors in the secondary prevention group, while prior major bleeding, alcohol abuse, advanced age, male sex, lower body weight, higher serum creatinine, and antiplatelet drug use were identified as risk factors for major hemorrhage, and advanced age and antiplatelet drug use for effectiveness outcomes in the primary prevention group. CONCLUSIONS: Among Japanese patients with nonvalvular atrial fibrillation who received apixaban, presence of a history of ischemic stroke/transient ischemic attack was associated with higher incidence rates of hemorrhage and thromboembolic events.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Ataque Isquêmico Transitório/prevenção & controle , Prevenção Primária , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Prospectivos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
4.
N Engl J Med ; 383(9): 825-835, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32846061

RESUMO

BACKGROUND: RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown. METHODS: We enrolled patients with RET-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated RET fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety. RESULTS: In the first 55 consecutively enrolled patients with RET-mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with RET-mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the percentage who had a response was 73% (95% CI, 62 to 82), and 1-year progression-free survival was 92% (95% CI, 82 to 97). In 19 patients with previously treated RET fusion-positive thyroid cancer, the percentage who had a response was 79% (95% CI, 54 to 94), and 1-year progression-free survival was 64% (95% CI, 37 to 82). The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), increased alanine aminotransferase level (in 11%), increased aspartate aminotransferase level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Of all 531 patients treated, 12 (2%) discontinued selpercatinib owing to drug-related adverse events. CONCLUSIONS: In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).


Assuntos
Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/induzido quimicamente , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-ret/análise , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Transaminases/sangue , Resultado do Tratamento , Adulto Jovem
5.
Lancet Haematol ; 7(9): e640-e648, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853584

RESUMO

BACKGROUND: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. METHODS: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 109 cells per L before major surgery or less than 50 × 109 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 109 cells per L before major surgery or 45 × 109 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204. FINDINGS: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; pnon-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; pnon-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. INTERPRETATION: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. FUNDING: GlaxoSmithKline and Novartis.


Assuntos
Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Pirazóis/uso terapêutico , Trombocitopenia/tratamento farmacológico , Administração Oral , Adulto , Idoso , Fibrilação Atrial/etiologia , Benzoatos/efeitos adversos , Feminino , Humanos , Hidrazinas/efeitos adversos , Imunoglobulinas Intravenosas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Assistência Perioperatória , Contagem de Plaquetas , Embolia Pulmonar/etiologia , Pirazóis/efeitos adversos , Resultado do Tratamento , Vertigem/etiologia
7.
N Engl J Med ; 383(9): 813-824, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32846060

RESUMO

BACKGROUND: RET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with RET fusion-positive NSCLC, the efficacy and safety of selective RET inhibition are unknown. METHODS: We enrolled patients with advanced RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated separately in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety. RESULTS: In the first 105 consecutively enrolled patients with RET fusion-positive NSCLC who had previously received at least platinum-based chemotherapy, the percentage with an objective response was 64% (95% confidence interval [CI], 54 to 73). The median duration of response was 17.5 months (95% CI, 12.0 to could not be evaluated), and 63% of the responses were ongoing at a median follow-up of 12.1 months. Among 39 previously untreated patients, the percentage with an objective response was 85% (95% CI, 70 to 94), and 90% of the responses were ongoing at 6 months. Among 11 patients with measurable central nervous system metastasis at enrollment, the percentage with an objective intracranial response was 91% (95% CI, 59 to 100). The most common adverse events of grade 3 or higher were hypertension (in 14% of the patients), an increased alanine aminotransferase level (in 12%), an increased aspartate aminotransferase level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). A total of 12 of 531 patients (2%) discontinued selpercatinib because of a drug-related adverse event. CONCLUSIONS: Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/induzido quimicamente , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-ret/análise , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Transaminases/sangue , Resultado do Tratamento , Adulto Jovem
8.
Khirurgiia (Mosk) ; (7): 68-75, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736466

RESUMO

The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.


Assuntos
Dabigatrana/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal/complicações , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Fatores Etários , Idoso , Antitrombinas , Dabigatrana/administração & dosagem , Idoso Fragilizado , Humanos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/complicações
9.
Clin Drug Investig ; 40(9): 839-845, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32607688

RESUMO

BACKGROUND AND OBJECTIVE: Current guidelines recommend anticoagulation with a vitamin K antagonist (warfarin) after a bioprosthetic valve replacement. There is minimal literature evaluating direct oral anticoagulants (DOACs) in patients who have just received a bioprosthetic aortic valve replacement (AVR) or mitral valve replacement (MVR). The purpose of this study was to investigate any differences in efficacy and safety for patients taking a DOAC, compared with warfarin, after a bioprosthetic AVR or MVR. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in patients who received bioprosthetic valve replacements at a large teaching hospital from 2014 to 2018. Patients included in this study received either warfarin or a DOAC following bioprosthetic AVR or MVR, and were maintained on the same agent throughout the 6-month follow-up period. The primary efficacy outcome was the incidence of thromboembolic complications and the primary safety outcome was the incidence of major bleeding within 6 months following surgery. The rate of readmission was assessed as a secondary endpoint. RESULTS: A total of 197 patients were included; 70 patients received warfarin and 127 patients received a DOAC (apixaban, n = 86; rivaroxaban, n = 40; dabigatran, n = 1). Three patients experienced thromboembolic events, all of which occurred in the DOAC group (0% vs. 2.4%; p = 0.20). Major bleeding occurred in 11 patients-two in the warfarin group and nine in the DOAC group (2.9% vs. 7.1%; p = 0.22). Sixty-one patients were readmitted within the 6-month time frame, with 26 readmissions in the warfarin group and 35 readmissions in the DOAC group (37% vs. 27%; p = 0.16). CONCLUSIONS: This small, exploratory study found similar rates of thromboembolic complications and major bleeding events in patients who received a DOAC versus warfarin after a recent bioprosthetic AVR or MVR. This study was limited by its retrospective nature and its sample size. Larger, randomized controlled trials are needed to further determine the efficacy and safety of DOACs in this patient population.


Assuntos
Anticoagulantes/uso terapêutico , Bioprótese , Dabigatrana/uso terapêutico , Próteses Valvulares Cardíacas , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tromboembolia/induzido quimicamente , Varfarina/administração & dosagem , Varfarina/efeitos adversos
10.
Stroke ; 51(8): 2364-2373, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640949

RESUMO

BACKGROUND AND PURPOSE: The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease. METHODS: Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses. RESULTS: A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51-0.96) for apixaban, 0.80 (0.54-1.17) for rivaroxaban, and 1.15 (0.69-1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37-0.59) for apixaban, 1.05 (0.85-1.30) for rivaroxaban, and 0.95 (0.70-1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar. CONCLUSIONS: Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Medicare , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Varfarina/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medicare/tendências , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Estados Unidos/epidemiologia , Varfarina/efeitos adversos , Adulto Jovem
11.
Anticancer Res ; 40(7): 4059-4066, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620653

RESUMO

BACKGROUND/AIM: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. PATIENTS AND METHODS: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group. RESULTS: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy. CONCLUSION: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Polônia , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Recidiva , Análise de Sobrevida , Resultado do Tratamento
12.
J Stroke Cerebrovasc Dis ; 29(8): 104982, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689586

RESUMO

We report a case of ophthalmic artery occlusion (OAO) in a young patient with COVID-19 infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT). A 48-year-old man with obesity was hospitalized with a severe form of COVID-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia. Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1 mg/kg twice daily. D-dimer level decreased to 4.98 µg/ml FEU while on therapeutic anticoagulation. Three weeks later pending hospital discharge, the anticoagulation was switched to oral apixaban 10 mg twice daily. Patient developed acute severe right eye visual loss of no light perception and was diagnosed with incomplete OAO. D-Dimer was elevated at 2.13 µg/ml FEU. Stroke etiological work-up found no embolic sources, resolution of the dilated cardiomyopathy and negative antiphospholipid antibodies. Treatment was changed to enoxaparin and no thrombotic events were encountered to date. Ocular vascular complications have not yet been reported in COVID-19. Controversy exists on the best management algorithm for the hypercoagulable state associated to COVID-19 Either direct oral anticoagulants or low-molecular-weight-heparin are considered appropriate at discharge for patients with venous thromboembolism. The optimum regimen for ischemic stroke prevention and the significance of D-Dimer for anticoagulation monitoring in COVID-19 remain unclear.


Assuntos
Arteriopatias Oclusivas/etiologia , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Artéria Oftálmica , Pneumonia Viral/tratamento farmacológico , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Trombose Venosa/tratamento farmacológico , Arteriopatias Oclusivas/diagnóstico por imagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Substituição de Medicamentos , Enoxaparina/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/virologia
13.
Am Heart J ; 227: 91-99, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32693197

RESUMO

Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design. DESIGN: PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year. SUMMARY: PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.


Assuntos
Anticoagulantes/uso terapêutico , Valva Aórtica/cirurgia , Inibidores do Fator Xa/uso terapêutico , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/prevenção & controle , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tromboembolia/prevenção & controle , Trombose/prevenção & controle , Varfarina/uso terapêutico , Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Desenho de Prótese , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Resultado do Tratamento , Varfarina/efeitos adversos
14.
J Allergy Clin Immunol ; 146(4): 786-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32710973

Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hipersensibilidade a Drogas/etiologia , Fatores Imunológicos/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/administração & dosagem , Amidas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Indóis/administração & dosagem , Indóis/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Índice de Gravidade de Doença
15.
Lancet ; 396(10244): 110-120, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32653055

RESUMO

BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment. METHODS: We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304. FINDINGS: Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups. INTERPRETATION: Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo. FUNDING: Incyte.


Assuntos
Inibidores de Janus Quinases/uso terapêutico , Pirazóis/uso terapêutico , Vitiligo/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Humanos , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Creme para a Pele/administração & dosagem , Resultado do Tratamento
16.
JAMA Netw Open ; 3(6): e207410, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589230

RESUMO

Importance: Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic. Objective: To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer. Design, Setting, and Participants: This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019. Interventions: Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily). Main Outcomes and Measures: The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction. Results: Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 patients [58.8%]; OR, 0.06; 95% CI, 0.01-0.25; P < .001) and pain associated with taking the medication (4 patients [2.1%] vs 92 patients [49.2%]; OR, 9.20; 95% CI, 2.67-31.82; P < .001). Conclusions and Relevance: These findings suggest that oral apixaban is a potentially safe, less painful, and easier-to-take alternative to subcutaneous enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The efficacy of apixaban to prevent venous thromboembolic events is hypothesized as being equivalent. Trial Registration: ClinicalTrials.gov Identifier: NCT02366871.


Assuntos
Anticoagulantes , Enoxaparina , Complicações Pós-Operatórias , Pirazóis , Piridonas , Tromboembolia Venosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Feminino , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Qualidade de Vida , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Adulto Jovem
17.
J Cardiovasc Pharmacol Ther ; 25(6): 523-530, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32476465

RESUMO

BACKGROUND: Direct-acting oral anticoagulants are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients after undergoing cardiac surgery is poorly defined despite a high prevalence of postoperative atrial fibrillation in this population. METHODS: Patients diagnosed with postoperative atrial fibrillation were prospectively randomized to warfarin or apixaban. Safety, efficacy, and economic outcomes were evaluated until their 4- to 6-week postoperative appointment. RESULTS: While this pilot study was not powered to determine a difference in safety or efficacy, adverse event rates were similar to the published literature. It was noted that a patient's course of therapy when utilizing apixaban was significantly less costly than warfarin when including medication, bridging, and laboratory expenses. CONCLUSION: Apixaban and warfarin both appeared to be safe and effective for anticoagulation throughout the duration of this pilot study in treating postoperative atrial fibrillation after coronary artery bypass grafting. Apixaban was associated with significantly less expense when bridging and monitoring costs were included in addition to medication expense.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Ponte de Artéria Coronária/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/economia , Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/economia , Análise Custo-Benefício , Custos de Medicamentos , Monitoramento de Medicamentos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Dakota , Projetos Piloto , Estudos Prospectivos , Pirazóis/efeitos adversos , Pirazóis/economia , Piridonas/efeitos adversos , Piridonas/economia , Fatores de Tempo , Resultado do Tratamento , Varfarina/efeitos adversos , Varfarina/economia
19.
Clin Imaging ; 65: 15-17, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32353713

RESUMO

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer. This targeted cancer therapy agent has been shown to have superior efficacy over standard chemotherapy in this small subset of lung cancer patients. An adverse effect of this drug therapy is the development of complex renal cysts. Here, we present a case of a 68-year-old patient with non-small cell lung cancer on Crizotinib therapy who developed complex bilateral renal cysts. It is important to recognize this drug-related complication in order to avoid mistaking it for disease progression, primary renal malignancy, or renal infection.


Assuntos
Antineoplásicos/uso terapêutico , Crizotinibe/uso terapêutico , Doenças Renais Císticas/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Idoso , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/uso terapêutico
20.
Am J Gastroenterol ; 115(9): 1513-1524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467502

RESUMO

INTRODUCTION: The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, and apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests. METHODS: Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010 and 2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities, and medications by propensity score on a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression. RESULTS: After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% confidence interval: 0.58-0.89). When comparing individual NOACs, only dabigatran (hazard ratio: 0.63; 95% confidence interval: 0.48-0.82) was associated with a lower risk of liver injury. DISCUSSION: Among patients with AF, NOACs as a group, and dabigatran alone were associated with a significantly lower risk of laboratory-based liver injury when compared with warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dabigatrana/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Dabigatrana/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Risco , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico
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