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1.
PLoS Med ; 21(7): e1004400, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38950074

RESUMO

BACKGROUND: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. METHODS AND FINDINGS: This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. CONCLUSIONS: In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.


Assuntos
Fibrilação Atrial , Dabigatrana , Inibidores do Fator Xa , Neoplasias , Humanos , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Neoplasias/mortalidade , Neoplasias/epidemiologia , Dinamarca/epidemiologia , Masculino , Feminino , Idoso , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Dabigatrana/uso terapêutico , Dabigatrana/efeitos adversos , Estudos de Coortes , Sistema de Registros , Rivaroxabana/uso terapêutico , Rivaroxabana/efeitos adversos , Fatores de Risco , Incidência , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos
3.
J Stroke Cerebrovasc Dis ; 33(6): 107310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636321

RESUMO

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.


Assuntos
Anticoagulantes , Antitrombinas , Heparina , Hirudinas , Fragmentos de Peptídeos , Proteínas Recombinantes , Trombocitopenia , Humanos , Masculino , Pessoa de Meia-Idade , Falso Aneurisma/cirurgia , Falso Aneurisma/tratamento farmacológico , Aneurisma Roto/cirurgia , Aneurisma Roto/diagnóstico por imagem , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Substituição de Medicamentos , Procedimentos Endovasculares/efeitos adversos , Heparina/efeitos adversos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento
4.
Am J Cardiovasc Drugs ; 24(3): 385-398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683263

RESUMO

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.


Assuntos
Antitrombinas , Heparina , Hirudinas , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Proteínas Recombinantes , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Hirudinas/efeitos adversos , Hirudinas/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina/administração & dosagem , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Eur J Clin Pharmacol ; 80(8): 1141-1150, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38605248

RESUMO

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.


Assuntos
Fibrilação Atrial , Dabigatrana , Hemorragia , Rivaroxabana , Humanos , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Dabigatrana/administração & dosagem , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Rivaroxabana/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Masculino , Feminino , Idoso , Hemorragia/induzido quimicamente , Estudos Retrospectivos , Pessoa de Meia-Idade , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Antitrombinas/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Idoso de 80 Anos ou mais , Tromboembolia/prevenção & controle
6.
Crit Rev Oncol Hematol ; 197: 104347, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583546

RESUMO

Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for primary VTE prevention has been studied with no consensus. We conducted a systematic literature search in PubMed, Scopus, and Web of science and performed random-effect meta-analysis using Mantel-Haenszel method in RevMan 5.4 to analyze primary pharmacological thromboprophylaxis during asparaginase treatment in early-phase (induction, consolidation, or intensification phase) therapy in patients with ALL with all ages and followed with subgroup analysis by age. Meta-analysis of 13 articles describing the effect of antithrombin supplementation in 1375 patients showed that antithrombin prophylaxis decreases the risk of VTE by 43% (RR, 0.57; 95% CI, 0.38 - 0.83; p=0.004), with mild heterogeneity (I2=35%, p=0.10) and moderate certainty by GRADE. 8 articles included for meta-analysis of low-molecular weight heparin (LMWH) treatment in 612 patients showed that it decreased the risk of VTE by nearly 40% (RR, 0.61; 95% CI, 0.45 - 0.81; p=0.00081), with minimal heterogeneity (I2=14%, p=0.31) but low certainty. Subgroup analysis showed that only prophylaxis with antithrombin supplementation significantly decreased the VTE rate in adult patients with moderate certainty. In pediatric patients, one nonrandomized prospective study showed that LMWH combined with antithrombin has a better thromboprophylaxis effect than antithrombin alone. In the PREVAPIX-ALL trial, prophylaxis with direct factor Xa inhibitor Apixaban did not benefit children younger than 18 years except for cases of obesity. We concluded that thromboprophylaxis with antithrombin is effective in ALL patients older than 18 years during the early phase of therapy, and LMWH combined with antithrombin supplementation might be effective for pediatric patients with ALL. Apixaban is effective in pediatric ALL patients with obesity and needs further study in other high-risk patients.


Assuntos
Asparaginase , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tromboembolia Venosa , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Antitrombinas/administração & dosagem , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos
8.
Am J Ther ; 31(4): e362-e371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525959

RESUMO

BACKGROUND: Dabigatran directly inhibits thrombin and is used in primary and secondary stroke prevention in individuals with nonvalvular atrial fibrillation. The prodrug dabigatran etexilate is absorbed by enteral P-glycoprotein (ABCB1) and then activated by hepatic and intestinal carboxylesterases (CES1) to produce active metabolites. Variations in dabigatran metabolism because of genetics may affect concentration levels and clinical outcomes. STUDY QUESTION: We conducted a study to assess how polymorphisms in the CES1 (rs2244613) and ABCB1 (rs4148738) genes affect the through plasma level (c min ) of dabigatran and its correlation to clinical outcomes. STUDY DESIGN: Retrospective multicentric study of consecutive patients on dabigatran therapy. Examination of CES1 rs2244613 and ABCB1 rs4148738 polymorphisms, c min 12 hours after administration, clinical follow-up (ischemic stroke, major or clinically relevant hemorrhage, myocardial infarction, other thromboembolism, and death). MEASURES AND OUTCOMES: A total of 432 patients received treatment for an average of 19.78 months (SD of 20.165). The sex distribution of the patients was 56.5% male, and the average age was 67.56 years (SD of 14.7). The ABCB1 variant genotype was present in 67.8% of patients, whereas 37.5% carried the CES1 polymorphism. RESULTS: Compared with wild-type patients, patients with the CES1 variant had significantly lower dabigatran plasma levels (with a mean difference of 16.986; 95% confidence interval, 5.794-28.178 ng/mL, P = 0.003). We also found a significant risk of major bleeding in patients carrying the ABCB1 rs4148738 allele (hazard ratio = 1.99, confidence interval 95% 1.10 to 3.59, P = 0.024). CONCLUSIONS: The CES1 variant genotype rs2244613 is closely linked with reduced c min of dabigatran. Carriers of the ABCB1 rs4148738 polymorphism exhibit a tendency toward higher plasma levels of dabigatran, which leads to a significantly increased risk of bleeding.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Antitrombinas , Hidrolases de Éster Carboxílico , Dabigatrana , Hemorragia , AVC Isquêmico , Humanos , Dabigatrana/efeitos adversos , Dabigatrana/farmacocinética , Dabigatrana/sangue , Dabigatrana/administração & dosagem , Masculino , Feminino , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Estudos Retrospectivos , AVC Isquêmico/prevenção & controle , AVC Isquêmico/genética , AVC Isquêmico/sangue , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/sangue , Pessoa de Meia-Idade , Antitrombinas/efeitos adversos , Antitrombinas/sangue , Antitrombinas/farmacocinética , Antitrombinas/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/sangue , Polimorfismo de Nucleotídeo Único , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Fibrilação Atrial/complicações , Fibrilação Atrial/sangue , Idoso de 80 Anos ou mais
9.
J Vasc Surg Venous Lymphat Disord ; 12(4): 101848, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38346475

RESUMO

BACKGROUND: Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT). METHODS: The RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular-weight-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months. RESULTS: There were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% vs 73.1% in the dabigatran and warfarin groups, respectively (P = .15). Complete recanalization occurred in 28.0% vs 19.2% in the dabigatran and warfarin groups, respectively (P = .56). The groups did not differ in the frequency of major bleeding events according to the International Society for Thrombosis and Hemostasis (0% vs 3.2% in the dabigatran and warfarin groups, respectively; P = 1.00). However, there were more nonmajor bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0%, respectively; P = .02). CONCLUSIONS: The results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for the treatment and prevention of PE after CDT with RDT in patients with high and intermediate to high PE risk.


Assuntos
Anticoagulantes , Antitrombinas , Dabigatrana , Embolia Pulmonar , Terapia Trombolítica , Varfarina , Humanos , Dabigatrana/efeitos adversos , Dabigatrana/administração & dosagem , Varfarina/efeitos adversos , Varfarina/administração & dosagem , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Masculino , Feminino , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Pessoa de Meia-Idade , Terapia Trombolítica/efeitos adversos , Idoso , Resultado do Tratamento , Estudos Prospectivos , Antitrombinas/efeitos adversos , Antitrombinas/administração & dosagem , Doença Aguda , Fatores de Tempo , Recidiva , Adulto , beta-Alanina/análogos & derivados , beta-Alanina/efeitos adversos , beta-Alanina/administração & dosagem , Fatores de Risco , Hemorragia/induzido quimicamente , Coeficiente Internacional Normatizado
10.
Eur Heart J Cardiovasc Pharmacother ; 10(3): 263-264, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38285615
11.
Cardiovasc Revasc Med ; 61: 52-61, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37872022

RESUMO

BACKGROUND: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. METHODS: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). CONCLUSION: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Trombose , Humanos , Heparina/efeitos adversos , Antitrombinas/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Hirudinas/efeitos adversos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Infarto do Miocárdio/complicações , Fragmentos de Peptídeos/efeitos adversos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Acidente Vascular Cerebral/etiologia , Trombose/etiologia , Proteínas Recombinantes/efeitos adversos , Anticoagulantes/efeitos adversos
12.
Braz J Med Biol Res ; 56: e13013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970924

RESUMO

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Heparina/efeitos adversos , Estudos Retrospectivos , Antitrombinas/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , População do Leste Asiático , Resultado do Tratamento , Hirudinas/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Fragmentos de Peptídeos/efeitos adversos , Fibrinolíticos , Proteínas Recombinantes/efeitos adversos
13.
Neurol Neurochir Pol ; 57(6): 465-476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37955597

RESUMO

INTRODUCTION: Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS). CLINICAL RATIONALE FOR THE STUDY: New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment. MATERIAL AND METHODS: Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0-2 points at discharge. RESULTS: This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0-2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Adolescente , Dabigatrana/uso terapêutico , Dabigatrana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Anticoagulantes/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos , Ativador de Plasminogênio Tecidual , Terapia Trombolítica/efeitos adversos , AVC Isquêmico/tratamento farmacológico , Resultado do Tratamento
14.
Expert Rev Cardiovasc Ther ; 21(12): 901-911, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37919937

RESUMO

INTRODUCTION: Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). AREAS COVERED: Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH. EXPERT OPINION: In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Resultado do Tratamento , Hirudinas/efeitos adversos , Heparina/efeitos adversos , Antitrombinas/efeitos adversos , Anticoagulantes/efeitos adversos , Fragmentos de Peptídeos/efeitos adversos , Hemorragia/induzido quimicamente , Proteínas Recombinantes/efeitos adversos
16.
Coron Artery Dis ; 34(8): 562-579, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37865864

RESUMO

BACKGROUND: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days. CONCLUSION: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Humanos , Heparina/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Antitrombinas/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Hirudinas/efeitos adversos , Anticoagulantes/efeitos adversos , Fragmentos de Peptídeos/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle , Proteínas Recombinantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
J Stroke Cerebrovasc Dis ; 32(9): 107268, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37487321

RESUMO

OBJECTIVES: People with arteriosclerotic cardiovascular diseases (ASCVD) frequently use antithrombotic agents and statins. The objective of the study was to explore the prevalence and risk factors of cerebral microbleeds (CMBs) in elderly (≥ 65 years old) Chinese people with ASCVD. MATERIALS AND METHODS: We prospectively included 755 eligible participants with complete MRI data, and CMBs were discerned on the SWI sequence. Multivariate logistic regression was performed to analyze risk factors associated with CMBs. RESULTS: The average age was 74.9 ± 9.5 years, and the prevalence of CMBs was 37.9% (286/755). Of those with CMBs, 65.0% (186/286) had strictly lobar CMBs, 35.0% (100/286) had deep or infratentorial CMBs with or without lobar CMBs. We divided CMBs into two groups according to their locations, lobar CMBs group (strictly lobar CMBs) and deep CMBs group (with or without lobar CMBs). Age per 10 years (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.17-1.72, p < 0.001), statin use (OR 1.54, 95% CI 1.05-2.26, p = 0.03), and lacunes (OR 1.70, 95% CI 1.09-2.68, p = 0.02) were associated with any CMBs. Age per 10 years (OR 1.33, 95% CI 1.10-1.63, p < 0.001), statin use (OR 1.67, 95% CI 1.12-2.50, p = 0.01), and white matter hyperintensities (OR 1.71, 95% CI 1.17-2.51, p < 0.01) were associated with lobar CMBs. Only lacunes were associated with deep CMBs (OR 3.29, 95% CI 1.85-5.87, p < 0.001). CONCLUSIONS: In elderly people with risk factors of ASCVD, antithrombotic drug use was not associated with any CMBs, lobar CMBs, or deep CMBs. Statin use was correlated with lobar CMBs but not deep CMBs.


Assuntos
Doenças Cardiovasculares , Hemorragia Cerebral , Inibidores de Hidroximetilglutaril-CoA Redutases , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Doenças Cardiovasculares/complicações , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , População do Leste Asiático , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imageamento por Ressonância Magnética/efeitos adversos , Prevalência , Fatores de Risco , Aterosclerose , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico
20.
Ann Intern Med ; 176(8): JC92, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523702

RESUMO

SOURCE CITATION: Wang X, Ma Y, Hui X, et al. Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis. Cochrane Database Syst Rev. 2023;4:CD010956. 37058421.


Assuntos
Anticoagulantes , Tromboembolia Venosa , Humanos , Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Antitrombinas/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Administração Oral
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