Enoxaparin for Long-Term Therapy of Venous Thromboembolism in Patients with Cancer and Renal Insufficiency.

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high risk of bleeding. METHODS: We used the Registro Informatizado Enfermedad Tromboemb00F3lica (RIETE) registry to compare the 6-month incidence rates of (1) VTE recurrences versus major bleeding and (2) fatal pulmonary embolism (PE) versus fatal bleeding in three subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy. RESULTS: From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild RI, 1,168 (41%) moderate RI, and 244 (8.6%) had severe RI. Overall, 68, 62, and 12%, respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences versus major bleeding (4.6 vs. 5.4%) and fatal PE versus fatal bleeding (1.3 vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1 vs. 6.3%), but fatal PE and fatal bleeding were close (1.8 vs. 1.2%). Among patients with severe RI, VTE recurrences were threefold less common than major bleeding (4.1 vs. 13%), but fatal PE was threefold more frequent than fatal bleeding (2.5 vs. 0.8%). During the first 10 days, fatal PE was fivefold more common than fatal bleeding (2.1 vs. 0.4%). CONCLUSION: Among cancer patients with severe RI, fatal PE was fivefold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study.

PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA). METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups. RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed. CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (ß = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Caracterización y eventos adversos relacionados con la asistencia sanitaria en pacientes infectados por el SARS-CoV-2 fallecidos en un hospital de tercer nivel / Patient characterization and adverse health care-related events in SARS-CoV-2 infected patients who died in a tertiary hospital

Objetivo: Caracterizar los episodios adversos relacionados con la asistencia sanitaria en pacientes infectados por SARS-CoV-2 fallecidos en un hospital de tercer nivel.MétodosEstudio observacional retrospectivo en el que se incluyeron los pacientes fallecidos en el centro entre el 16 de marzo y el 10 de abril de 2020. La información fue extraída desde la historia clínica electrónica.ResultadosLa mediana de edad de los 164 pacientes analizados fue de 77,5 años. Más de 9 de cada 10 pacientes fallecidos presentaban al menos una comorbilidad. El 40,2% de los pacientes presentó al menos un episodio adverso (EA) asociado a la atención sanitaria. Un 23,8% de los pacientes presentó alguna reacción adversa a medicamentos, constituyendo la primera causa de EA entre los pacientes fallecidos. Entre los pacientes que fallecieron en unidades de cuidados intensivos, los problemas relacionados con la ventilación mecánica han aparecido con una frecuencia del 8,8%.ConclusionesA pesar de que la letalidad asociada a los EA detectados fue muy reducida, es fundamental establecer una vigilancia estrecha de los posibles EA asociados a la asistencia sanitaria, especialmente los farmacológicos, dado que se trata de una enfermedad con un tratamiento terapéutico incierto. (AU)

Objective: To characterize health care-related adverse events in patients with SARS-CoV-2 infection who died in a tertiary hospital.MethodsThis is a retrospective, observational study, that included patients who died at HUGTiP hospital between 16 March and 10 April 2020. Data was extracted from the electronic medical record.ResultsThe median age of the 164 SARS-CoV-2 infected patients who died in the center in the study period was 77.5 years and> 90% of patients had ≥ 1 comorbidity. Forty point two percent of patients had at least ≥ 1 health care-related adverse event. Twenty three point eight of patients had an adverse drug reaction, the leading cause of adverse events in patients who died. Of patients who died in intensive care units, the frequency of problems related to mechanical ventilation was 8.8%.ConclusionsAlthough the case fatality rate associated with the adverse events detected was very low, close monitoring of potential health care-related adverse events, especially drug reactions, as the therapeutic management of the disease remains unclear. (AU)

Patient characterization and adverse health care-related events in SARS-CoV-2 infected patients who died in a tertiary hospital.

OBJECTIVE: To characterize health care-related adverse events in patients with SARS-CoV-2 infection who died in a tertiary hospital. METHODS: This is a retrospective, observational study, that included patients who died at HUGTiP hospital between 16 March and 10 April 2020. Data was extracted from the electronic medical record. RESULTS: The median age of the 164 SARS-CoV-2 infected patients who died in the center in the study period was 77.5 years and >90% of patients had ≥1 comorbidity. Forty point two percent of patients had at least ≥1 health care-related adverse event. Twenty three point eight of patients had an adverse drug reaction, the leading cause of adverse events in patients who died. Of patients who died in intensive care units, the frequency of problems related to mechanical ventilation was 8.8%. CONCLUSIONS: Although the case fatality rate associated with the adverse events detected was very low, close monitoring of potential health care-related adverse events, especially drug reactions, as the therapeutic management of the disease remains unclear.

OBJETIVO: Caracterizar los eventos adversos relacionados con la asistencia sanitaria en pacientes infectados por SARS-CoV-2 fallecidos en un hospital de tercer nivel. MÉTODOS: Estudio observacional retrospectivo en el que se incluyeron los pacientes fallecidos en el centro entre el 16 de marzo y el 10 de abril de 2020. La información fue extraída desde la historia clínica electrónica. RESULTADOS: La mediana de edad de los 164 pacientes analizados fue de 77,5 años. Más de 9 de cada 10 pacientes fallecidos presentaban al menos una comorbilidad. El 40,2% de los pacientes presentó al menos un evento adverso (EA) asociado a la atención sanitaria. Un 23,8% de los pacientes presentó alguna reacción adversa a medicamentos, constituyendo la primera causa de EA entre los pacientes fallecidos. Entre los pacientes que fallecieron en unidades de cuidados intensivos, los problemas relacionados con la ventilación mecánica han aparecido con una frecuencia del 8,8%. CONCLUSIONES: A pesar de que la letalidad asociada a los EA detectados fue muy reducida, es fundamental establecer una vigilancia estrecha de los posibles EA asociados a la asistencia sanitaria, especialmente los farmacológicos, dado que se trata de una enfermedad con un manejo terapéutico incierto.

[Patient characterization and adverse health care-related events in SARS-CoV-2 infected patients who died in a tertiary hospital]. / Caracterización y eventos adversos relacionados con la asistencia sanitaria en pacientes infectados por el SARS-CoV-2 fallecidos en un hospital de tercer nivel.

OBJECTIVE: To characterize health care-related adverse events in patients with SARS-CoV-2 infection who died in a tertiary hospital. METHODS: This is a retrospective, observational study, that included patients who died at HUGTiP hospital between 16 March and 10 April 2020. Data was extracted from the electronic medical record. RESULTS: The median age of the 164 SARS-CoV-2 infected patients who died in the center in the study period was 77.5 years and> 90% of patients had ≥ 1 comorbidity. Forty point two percent of patients had at least ≥ 1 health care-related adverse event. Twenty three point eight of patients had an adverse drug reaction, the leading cause of adverse events in patients who died. Of patients who died in intensive care units, the frequency of problems related to mechanical ventilation was 8.8%. CONCLUSIONS: Although the case fatality rate associated with the adverse events detected was very low, close monitoring of potential health care-related adverse events, especially drug reactions, as the therapeutic management of the disease remains unclear.

Clinical characteristics and 3-month outcomes in cancer patients with incidental versus clinically suspected and confirmed pulmonary embolism.

BACKGROUND: Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared. METHODS: We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PE versus those with clinically suspected and confirmed PE. The primary outcome was 90-day all-cause mortality. Secondary outcomes were PE-related mortality, symptomatic PE recurrences and major bleeding. RESULTS: From July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95% versus 90%) received low-molecular-weight heparin therapy. During the first 90 days, 598 patients died, including 42 from PE. Patients with incidental PE had a lower all-cause mortality rate than those with suspected and confirmed PE (11% versus 22%; OR 0.43, 95% CI 0.34-0.54). Results were consistent for PE-related mortality (0.3% versus 1.7%; OR 0.18, 95% CI 0.06-0.59). Multivariable analysis confirmed that patients with incidental PE were at lower risk of death (adjusted OR 0.43, 95% CI 0.34-0.56). Overall, 29 (0.9%) patients developed symptomatic PE recurrences, and 122 (3.8%) had major bleeding. There were no significant differences in PE recurrences (OR 0.62, 95% CI 0.25-1.54) or major bleeding (OR 0.78, 95% CI 0.51-1.18). CONCLUSIONS: Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.

Índices de riesgo de recurrencia en la enfermedad tromboembólica venosa no provocada / Predicting risk indices of recurrence in the unprovoked venous thromboembolic disease

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Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism.

INTRODUCTION: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared. MATERIAL AND METHODS: We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy. RESULTS: From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06). CONCLUSION: The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding.

Comparing low-molecular-weight heparin dosing for treatment of venous thromboembolism in patients with obesity (RIETE registry).

Because of the absence of comparative evidence, current guidelines and product monographs diverge in the dosing of low-molecular-weight heparin (LMWH) for obese patients with venous thromboembolism (VTE). We used the RIETE registry to compare the primary composite outcomes (VTE recurrence, major bleeding, or death) in patients with VTE who weighed >100 kg during LMWH therapy with capped doses of LMWH (18 000 IU/d) vs uncapped doses (>18 000 IU/d). Multivariable logistic regression analysis was used to account for possible confounders. A total of 2846 patients who weighed >100 kg were included: 454 (16%) received capped doses of LMWH, and the remaining 2392 received uncapped doses. Mean (standard deviation) LMWH treatment duration was 14.8 (20.6) and 14.3 (32.3) days, respectively. Thirty-one patients (1.9%) had VTE recurrences, 38 (1.3%) had bleeding episodes, 65 (2.3%) died, and 122 (4.3%) had at least 1 of the composite outcomes. Unadjusted outcome rates revealed that capped dosing was associated with a decrease in the composite outcome (rate ratio, 0.22; 95% confidence interval [CI], 0.04-0.75). Multivariable analysis confirmed that patients who received capped doses had significantly lower rates of the composite outcome (odds ratio, 0.16; 95% CI, 0.04-0.68) while receiving LMWH. These retrospective observational data suggest that capped dosing of LMWH is an acceptable alternative to uncapped dosing based on body weight, given the significantly lower composite event rate of VTE recurrence, major bleeding, and all-cause death.

Morbid Obesity and Mortality in Patients With VTE: Findings From Real-Life Clinical Practice.

BACKGROUND: The influence of morbid obesity on mortality in patients receiving anticoagulant therapy for VTE has not been consistently evaluated. METHODS: Data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry were used to compare the mortality risk during anticoagulation in patients with VTE and morbid obesity (BMI ≥ 40 kg/m2) vs those with normal weight (BMI, 18.5-24.9 kg/m2). Patients with or without active cancer were analyzed separately. RESULTS: By September 2018, there were 1,642 patients with VTE and morbid obesity and 14,848 with normal weight in RIETE. Of these, 245 (5.5%) and 1,397 (11.6%), respectively, had cancer. Median duration of anticoagulant therapy was longer in the morbidly obese patients, with cancer (185 vs 114 days) or without cancer (203 vs 177 days). Among cancer patients, 44 (18.0%) morbidly obese and 1,377 (32.8%) patients with normal weight died during anticoagulation. Among those without cancer, 44 (3.1%) morbidly obese died and 601 (5.6%) with normal weight died. On bivariate analysis, morbid obesity was associated with a lower mortality rate, both in patients with cancer (hazard ratio, 0.34; 95% CI, 0.25-0.45) and in those without cancer (hazard ratio, 0.43; 95% CI, 0.32-0.58). Multivariable analysis confirmed a lower hazard of death in morbidly obese patients with cancer (hazard ratio, 0.68; 95% CI, 0.50-0.94) and without cancer (hazard ratio, 0.67; 95% CI, 0.49-0.96). The risk for VTE recurrences or major bleeding did not differ in patients with or without morbid obesity. CONCLUSIONS: In patients with VTE, the risk for death during anticoagulation was about one-third lower in morbidly obese patients than in those with normal weight, independently of the presence of cancer.

Recent developments and persisting challenges in the prevention and treatment of venous thromboembolism in patients with hematological malignancies.

Venous thromboembolism (VTE) is a common complication of cancer. Its treatment is challenging because of the high risk for both VTE recurrence and bleeding. Evidence is particularly scarce for patients with hematological malignancies. This review aims to summarize new developments in anticoagulation for the prevention and treatment of VTE in patients with active cancer, largely derived from the formal introduction of direct anticoagulants (DOACs) in this population. We then offer our recommendations for the thromboprophylaxis and treatment of VTE in patients with hematological disorders (mature lymphoid disorders, plasma cell disorders, myeloproliferative neoplasms, myelodysplastic syndrome and acute leukemia/stem cell transplant). We conclude by emphasizing the lack of high-quality evidence in a majority of these settings, caution about the use of DOACs in clinical situations where evidence is lacking and, finally, note the importance of involving patients in the decision-making process.

Venous Thromboembolism in Patients With Autoimmune Disorders: Findings From the RIETE Registry.

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