RESUMO
Essentials Coronary artery bypass graft (CABG) failure is associated with myocardial infarction and death. We tested whether more frequent dosing improves aspirin (ASA) response following CABG surgery. Twice-daily compared with once-daily dosing reduces ASA hyporesponsiveness after CABG surgery. The efficacy of twice-daily ASA needs to be tested in a trial powered for clinical outcomes. SUMMARY: Background Acetyl-salicylic acid (ASA) hyporesponsiveness occurs transiently after coronary artery bypass graft (CABG) surgery and may compromise the effectiveness of ASA in reducing thrombotic graft failure. A reduced response to ASA 81 mg once-daily after CABG surgery is overcome by four times daily ASA dosing. Objectives To determine whether ASA 325 mg once-daily or 162 mg twice-daily overcomes a reduced response to ASA 81 mg once-daily after CABG surgery. Methods Adults undergoing CABG surgery were randomized to ASA 81 mg once-daily, 325 mg once-daily or 162 mg twice-daily. The primary outcome was median serum thromboxane B2 (TXB2 ) level on postoperative day 4. We pooled the results with those of our earlier study to obtain better estimates of the effect of ASA 325 mg once-daily or in divided doses over 24 h. Results We randomized 68 patients undergoing CABG surgery. On postoperative day 4, patients randomized to receive ASA 81 mg once-daily had a median day 4 TXB2 level of 4.2 ng mL-1 (Q1, Q3: 1.5, 7.5 ng mL-1 ), which was higher than in those randomized to ASA 162 mg twice-daily (1.1 ng mL-1 ; Q1, Q3: 0.7, 2.7 ng mL-1 ) and similar to those randomized to ASA 325 mg once-daily (1.9 ng mL-1 ; Q1, Q3: 0.9, 4.7 ng mL-1 ). Pooled data showed that the median TXB2 level on day 4 in groups receiving ASA 162 mg twice-daily or 81 mg four times daily was 1.1 ng mL-1 compared with 2.2 ng mL-1 in those receiving ASA 325 mg once-daily. Conclusions Multiple daily dosing of ASA is more effective than ASA 81 mg once-daily or 325 mg once-daily at suppressing serum TXB2 formation after CABG surgery. A twice-daily treatment regimen needs to be tested in a clinical outcome study.
Assuntos
Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Ponte de Artéria Coronária , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Plaquetas/metabolismo , Ponte de Artéria Coronária/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Tromboxano B2/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The rate of recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who had a negative qualitative D-dimer test one month after stopping anticoagulant therapy was higher than expected in the D-dimer Optimal Duration Study (DODS). OBJECTIVES: To determine whether quantitative D-dimer levels using a low threshold, age- and sex-specific thresholds, or repeated measurements, would improve identification of patients at low risk of recurrent VTE. MATERIALS AND METHODS: D-dimer levels were quantified in banked samples from 307 patients in DODS who had a negative qualitative D-dimer test while on, and 1month after stopping, anticoagulant therapy and the rates of recurrent VTE were determined in patients with D-dimer levels below various predefined thresholds. RESULTS: The rate (per patient year) of recurrent VTE was: 5.9% with D-dimer levels<250µg/l at one month; 5.2% with D-dimer levels between 250 and 499µg/l at one month; 5.0% with D-dimer levels less than predefined age- and sex-specific thresholds at one month; and 6.3% when D-dimer levels were <500µg/l at both one and 7months after stopping anticoagulant therapy. These rates are similar to the overall event rate of 6.3% in patients who stopped treatment. CONCLUSIONS: Among unprovoked VTE patients who had a negative qualitative D-dimer test during and after anticoagulant therapy, low D-dimer thresholds, age and sex-adjusted thresholds or repeated measurements, did not identify subgroups with a very low rate of recurrence.
Assuntos
Anticoagulantes/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tromboembolia Venosa/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Prognóstico , Recidiva , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: In clinical practice, physicians are given the choice of selecting one of two dabigatran doses based on patient characteristics, with the lower dose typically used in patients at a higher risk of bleeding. OBJECTIVES: The objectives of the study were to (i) estimate the inter- and intra-patient variability in dabigatran levels with 110 mg (DE110) and 150 mg (DE150) doses, (ii) examine the effect of physicians' dose selection on levels in DE110 and DE150 subgroups, and (iii) explore whether a single trough measurement identifies patients with extreme levels on subsequent visits. METHODS: In this prospective observational study of 100 patients with atrial fibrillation (AF), peak and trough levels of dabigatran were measured with the Hemoclot(®) assay at baseline and every 2 months thereafter (maximum four visits). RESULTS: Inter-patient variability in dabigatran levels (geometric coefficient of variation [gCV], 51-64%) was greater than intra-patient variability (gCV, 32-40%). Similar medians and distributions of levels were observed in DE110 and DE150 subgroups. Patients receiving DE110 were older, had lower renal function and weighed less than those receiving DE150. Up to 40% of patients whose trough levels were in the upper extremes, and up to 80% of patients whose trough levels were in the lower extremes at baseline, showed subsequent levels that fell in the middle quartiles. CONCLUSIONS: Our data support the practice of selecting the dabigatran dose based upon clinical characteristics because it results in similar levels of drug exposure in patients given DE110 or DE150. They do not support the concept that a single Hemoclot(®) measurement reliably identifies patients with consistently high or low values.
Assuntos
Antitrombinas/sangue , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Dabigatrana/sangue , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Testes de Coagulação Sanguínea , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post-operative platelet turnover. OBJECTIVES: To determine whether acetyl-salicylic acid (ASA) 325 mg once-daily or 81 mg four-times daily overcomes the impaired response to ASA 81 mg once-daily in post-operative coronary artery bypass graft (CABG) patients. METHODS: We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once-daily, 81 mg four times daily or 325 mg once-daily and compared their effects on serum thromboxane B2 (TXB2 ) suppression and arachidonate-induced platelet aggregation. RESULTS: One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post-operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once-daily and less evident in those receiving ASA four times daily. On post-operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once-daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P < 0.0001) or ASA 325 mg once-daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once-daily and 325 mg once-daily at suppressing platelet aggregation. CONCLUSIONS: Four times daily ASA is more effective than ASA 81 and 325 mg once-daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.
Assuntos
Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Ponte de Artéria Coronária , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Plaquetas/metabolismo , Ponte de Artéria Coronária/efeitos adversos , Esquema de Medicação , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Projetos Piloto , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Contagem de Plaquetas , Testes de Função Plaquetária , Tromboxano B2/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.
Assuntos
Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Síndrome Pós-Trombótica/etiologia , Trombose Venosa/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Canadá , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/prevenção & controle , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Meias de Compressão , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Trombose Venosa/complicações , Trombose Venosa/diagnóstico , Trombose Venosa/terapiaRESUMO
Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.
Assuntos
Dor Aguda/terapia , Extremidade Inferior/irrigação sanguínea , Meias de Compressão , Trombose Venosa/terapia , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Adulto , Idoso , Canadá , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/prevenção & controle , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Trombose Venosa/complicações , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Clinical situations occur where expedient assessment of the anticoagulant activity of the direct factor Xa (FXa) inhibitors is required. Although quantitative anti-FXa (FXa) assays can be used to measure plasma levels of apixaban or rivaroxaban, turnaround is often slow and many laboratories do not perform these assays. OBJECTIVE: We compared the in vitro effects of apixaban and rivaroxaban on two readily available laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (APTT), performed with different reagents. We aimed to identify the most sensitive reagents. METHODS: Rivaroxaban or apixaban was added to human plasma at a range of concentrations covering expected peak and trough levels, and concentrations were confirmed using calibrated anti-FXa assays. Samples were assayed with six PT and seven APTT reagents using different coagulometers. RESULTS AND CONCLUSIONS: TriniCLOT PT Excel S was the only reagent to demonstrate sensitivity to apixaban. All of the PT reagents were sensitive to rivaroxaban with TriniCLOT PT Excel S and HemosIL HS PLUS being the most sensitive. Sensitivity to rivaroxaban varied among APTT reagents; four reagents exhibited the greatest responsiveness, and of these, Actin FSL was the most responsive. Commonly used coagulation tests may be useful for assessing the anticoagulant effect of rivaroxaban but not of apixaban. The reason for the different effects of apixaban and rivaroxaban on the PT and APTT is unknown.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/farmacologia , Morfolinas/farmacologia , Tempo de Tromboplastina Parcial/métodos , Tempo de Protrombina/métodos , Pirazóis/farmacologia , Piridonas/farmacologia , Tiofenos/farmacologia , Relação Dose-Resposta a Droga , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , RivaroxabanaRESUMO
BACKGROUND: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS). OBJECTIVES: To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs. METHODS: Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ). RESULTS: The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of costs being attributable to non-medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40). CONCLUSIONS: The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.
Assuntos
Efeitos Psicossociais da Doença , Trombose Venosa/economia , Adulto , Idoso , Canadá , Feminino , Alocação de Recursos para a Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. OBJECTIVE: To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients. METHODS: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24months. D-dimer was measured at 4months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. RESULTS: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0µgL(-1) ; P=0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P=0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P=0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P=0.01). CONCLUSION: D-dimer levels, measured 4months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/biossíntese , Síndrome Pós-Trombótica/sangue , Insuficiência Venosa/sangue , Insuficiência Venosa/complicações , Trombose Venosa/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Síndrome Pós-Trombótica/complicações , Estudos Prospectivos , Fatores de Risco , Trombose Venosa/complicaçõesRESUMO
SUMMARY BACKGROUND: The role of D-dimer in excluding deep vein thrombosis (DVT) in pregnancy is currently uncertain. We hypothesized that the specificity of sensitive D-dimer assays could be improved without compromising sensitivity by using higher D-dimer cut-off values. OBJECTIVE: To determine the test characteristics of two rapid enzyme-linked immunosorbent assays and three latex agglutination assays in pregnancy. METHOD: We recruited consecutive pregnant women who presented to participating centers with suspected DVT for the study. Symptomatic women were investigated with compression ultrasonography, and received 3 months of clinical follow-up to assess for the presence of venous thrombosis. Plasma samples for D-dimer were collected and frozen at the time of presentation. The median and mean D-dimer values for respective trimesters of pregnancy in patients with and without DVT were calculated. Receiver operating curves (ROCs) were plotted for respective assays to establish the best cut-points. The test characteristics corresponding to standard cut-points and these 'pregnancy' cut-points are presented. RESULTS: The prevalence of DVT in our cohort was 6.6% (95% confidence interval 4.0-10.6%). The mean and median D-dimer values were significantly increased throughout pregnancy. Overall, women with confirmed DVT had higher D-dimer levels than women without DVT (P < 0.0001). Improved specificities (62-79%) were observed with the use of higher cut-points obtained from ROCs for all five assays, and high sensitivities were maintained (80-100%) for DVT diagnosis. CONCLUSION: Using higher cut-points than those used in non-pregnant patients, the specificity of D-dimer assays for the diagnosis of DVT in pregnancy can be improved without compromising sensitivity. Validation in prospective management studies is needed.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose Venosa/diagnóstico , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Humanos , Limite de Detecção , Curva ROCRESUMO
BACKGROUND: As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women. OBJECTIVES: To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT. METHODS: A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients. RESULTS: The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P = 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%; P = 0.025) or moderate (16.9% vs. 8.7%; P = 0.04), but similar in patients in the high category (40.2% vs. 44.0%; P = 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%; P < 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men. CONCLUSIONS: In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.
Assuntos
Trombose Venosa/epidemiologia , Trombose Venosa/patologia , Adulto , Idoso , Canadá/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Probabilidade , Estudos Prospectivos , Fatores Sexuais , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Patients with unprovoked venous thromboembolism (VTE) may be at increased risk of acute myocardial infarction (AMI). However, the nature and clinical significance of this association remain unclear, particularly as it relates to age of presentation. METHODS: We performed a longitudinal matched cohort study utilizing multiple administrative databases. Ontario residents aged 20-64 years diagnosed with unprovoked VTE from 1 April 1991 to 31 March 1995 (n = 6065) were matched to a population cohort (n = 12 040) in 1 : 2 fashion on the basis of age, gender, socioeconomic class, cardiovascular risk factors and other comorbidities. The primary outcome was a comparison of relative risk of AMI over 10-year follow-up in subjects with unprovoked VTE (overall and stratified by age) vs. controls. Secondary outcomes included risk of death or the composite endpoint of AMI and/or death. RESULTS: Patients 20-39 years of age presenting with unprovoked VTE had an increased risk of AMI [adjusted hazard ratio (HR) 3.92, 95% confidence interval (CI) 1.65-9.35] as compared to controls; the association was applicable to those without atherosclerotic risk factors at baseline. There was no significant relationship between unprovoked VTE and AMI among patients 40-64 years old, with or without atherosclerotic risk factors. Irrespective of age, patients with unprovoked VTE had an increased risk of all-cause death or our composite endpoint of AMI and/or death as compared to patients without VTE. CONCLUSIONS: Unprovoked VTE is associated with a nearly 4-fold higher risk of subsequent AMI among younger patient populations. Future studies must explore the risk-benefit tradeoffs of long-term surveillance and management options among such patient populations.
Assuntos
Infarto do Miocárdio/complicações , Tromboembolia Venosa/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia Venosa/mortalidadeRESUMO
BACKGROUND/OBJECTIVES: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). PATIENTS/METHODS: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. RESULTS: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores. CONCLUSIONS: Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.
Assuntos
Qualidade de Vida , Trombose Venosa/complicações , Trombose Venosa/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/etiologia , Prognóstico , Estudos Prospectivos , Inquéritos e Questionários , Trombose Venosa/tratamento farmacológicoAssuntos
Complicações Cardiovasculares na Gravidez/terapia , Embolia Pulmonar/terapia , Adulto , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina/uso terapêutico , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Primeiro Trimestre da Gravidez , Embolia Pulmonar/sangueRESUMO
BACKGROUND: LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development. OBJECTIVES: The aims of this proof-of-concept study in patients undergoing total knee replacement (TKR) or total hip replacement (THR) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism (VTE) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin. METHODS: In a double-blind, parallel-arm, dose-ranging study, patients undergoing TKR or THR were randomly allocated to receive once-daily oral LY517717 (25, 50, 75, 100, 125 or 150 mg), started 6-8 h after wound closure, or s.c. enoxaparin, 40 mg, started in the evening before surgery. The primary efficacy endpoint was the composite of deep venous thrombosis (DVT), detected by mandatory bilateral venography performed at the end of the study treatment (between days 5 and 9), and objectively confirmed symptomatic DVT and/or pulmonary embolism (PE), occurring during the treatment period. The combination of major and minor bleeding was the primary safety endpoint. RESULTS: Five hundred and seven patients received at least one dose of LY517717 or enoxaparin (safety population). Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and/or PE (primary efficacy population). LY517717 treatment resulted in a dose-dependent decrease in the incidence of thromboembolic events (P = 0.0001). The incidences of VTE with 100, 125, and 150 mg of LY517717 were 19%, 19% and 16%, respectively, compared to 21% with enoxaparin. The efficacies of 100-mg, 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria. Bleeding events were uncommon in both LY517717 and enoxaparin patients. CONCLUSIONS: Doses of 100, 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR, and are associated with similar low rates of bleeding.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Inibidores do Fator Xa , Glicina/análogos & derivados , Piperazinas/farmacologia , Complicações Pós-Operatórias , Tromboembolia/prevenção & controle , Trombose Venosa/prevenção & controle , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Glicina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia/etiologia , Resultado do Tratamento , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is uncommon and is associated with well-defined risk factors in the general population. Increasingly, UEDVTs are being reported during pregnancy, particularly those achieved with the use of assisted reproductive techniques (ART), and in conjunction with ovarian hyperstimulation syndrome (OHSS). AIM: We performed this review was to estimate the incidence of UEDVT associated with ART, to examine the risk factors and presentation of UEDVT in pregnancy, and to determine if differences exist between this cohort and the general population. RESULTS: There were 35 published case reports of UEDVT in pregnant women. The incidence of this condition is estimated to be 0.08-0.11% of treatment cycles in women undergoing ART. The development of UEDVT is not always be preceded by OHSS. In addition, commonly associated risk factors for UEDVT were not often reported for UEDVT that developed during pregnancy. Instead the association of UEDVT and ART was common. UEDVT in pregnancy also appears to involve the internal jugular vein more often than the subclavian vein. The reported risk of thrombus extension in this cohort, despite anticoagulation therapy, is also disconcerting. CONCLUSION: Because UEDVT may not be a rare entity during pregnancy in association with the use of ART, clinicians should be better informed of its presentation and clinical course in these women. Once UEDVT develops, appropriate therapeutic anticoagulation should be instituted and patient carefully monitored. The long-term implications and recurrence rate of this condition in pregnancy warrants further prospective studies.
Assuntos
Complicações Cardiovasculares na Gravidez , Técnicas de Reprodução Assistida , Extremidade Superior/irrigação sanguínea , Trombose Venosa/diagnóstico , Trombose Venosa/terapia , Feminino , Humanos , Incidência , Síndrome de Hiperestimulação Ovariana/complicações , Gravidez , Resultado da Gravidez , Trombose Venosa/complicaçõesRESUMO
INTRODUCTION: Diagnosing deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnancy is challenging. Many of the common diagnostic tests, including compression ultrasonography (CUS), ventilation-perfusion scintigraphy (VQ scan) and helical computed tomography (hCT) that have been extensively investigated in non-pregnant patients, have not been appropriately validated in pregnancy. Extrapolating results of diagnostic studies of DVT and PE in non-pregnant patients to those who are pregnant may not be correct because during pregnancy, physiologic and anatomic changes may affect diagnostic test results, presentation and natural history of VTE. METHODS: We performed a systematic analysis of published studies addressing accurate diagnostic testing for DVT and PE in pregnancy to determine the accuracy of these tests in pregnancy. RESULTS: Our initial search yielded 530 articles of which four remained for inclusion, three studies investigating diagnostic testing in patients with a clinical suspicion of DVT or PE and one study in patients with a clinical suspicion of PE. CONCLUSIONS: From our systematic analysis of published studies investigating diagnostic testing for a clinical suspicion of DVT in pregnancy we conclude that; (i) two studies support withholding anticoagulant therapy in pregnant women with a clinical suspicion of DVT and normal results on serial IPG (impedance plethysmography), however, IPG is no longer used; (ii) one study demonstrated that a normal CUS at presentation combined with a normal D-dimer test or an abnormal D-dimer test combined with normal serial CUS appears promising for safely excluding DVT in pregnant patients, but too few patients were included in this pilot-study to draw firm conclusions; and (iii) one study investigated pregnant patients with a clinical suspicion of PE and this study concluded that in patients with normal or non-diagnostic VQ scans, withholding anticoagulant therapy might be safe, but this needs confirmation in larger studies. Recommendations on diagnostic testing of pregnant patients with a clinically suspected DVT or PE are provided.