Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Cardiac rehabilitation and outcome in stable outpatients with recent myocardial infarction.

OBJECTIVE: To compare the mortality rate and the rate of subsequent ischemic events (myocardial infarction [MI], ischemic stroke, or limb amputation) in patients with recent MI according to the use of cardiac rehabilitation or no rehabilitation. DESIGN: Longitudinal observational study. SETTING: Ongoing registry of outpatients. PARTICIPANTS: Patients (N=1043) with recent acute MI were recruited; of these, 521 (50%) participated in cardiac rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subsequent ischemic events and mortality rates were registered. RESULTS: Over a mean follow-up of 18 months, 50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence interval [CI], 0.0-0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54 events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2-0.7) were significantly lower in cardiac rehabilitation participants than in nonparticipants. Multivariate analysis confirmed that patients in cardiac rehabilitation had a significantly lower risk of death (hazard ratio=.08; 95% CI, .01-.63; P=.016) and a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95% CI, .30-1.42). CONCLUSIONS: The use of cardiac rehabilitation in patients with recent MI was independently associated with a significant decrease in the mortality rate and a nonsignificant decrease in the rate of subsequent ischemic events.

Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients. METHODS: COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)). RESULTS: Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7). CONCLUSIONS: COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients.

Edoxaban for the Long-Term Therapy of Venous Thromboembolism: Should the Criteria for Dose Reduction be Revised?

Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12-42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63-262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54-133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated.

Outcomes after Vena Cava Filter Use in Patients with Cancer-Associated Venous Thromboembolism and Contraindications to Anticoagulation.

BACKGROUND: The association between the use of inferior vena cava filters (IVCFs) and outcomes among patients with cancer-associated thromboembolism (CT) and contraindications to anticoagulation remains unclear. METHODS: In this prospective cohort study of patients with CT from the Registro Informatizado de la Enfermedad TromboEmbólica Registry, we assessed the association between IVCF insertion due to contraindication to anticoagulation and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent thromboembolism, and major bleeding rates through 30 days after initiation of treatment. We used propensity score matching to adjust for the likelihood of receiving a filter. For outcomes assessment, we implemented generalized estimating equation methods to incorporate the matched-pairs design, and adjusted for covariates that remained unbalanced after matching. RESULTS: Of the 17,005 patients with CT, 270 underwent IVCF placement because of contraindication to anticoagulation. Of those, 247 were successfully matched with 247 patients treated without a filter. Propensity score-matched pairs showed a nonsignificantly lower risk of all-cause death (12.2% vs. 17.0%; p = 0.13), and a significantly lower risk of PE-related mortality (0.8% vs. 4.0%; p = 0.04) for patients receiving IVCFs compared with those who did not. While there was no significant difference in the rate of major bleeding (6.1% vs. 5.7%; p = 0.85), risk-adjusted recurrent rates were higher for patients who received IVCFs compared with those who did not (7.3% vs. 3.2%; p = 0.05). CONCLUSION: In patients with CT and a contraindication to anticoagulation, IVCF insertion was associated with a lower risk of PE-related death, and a higher risk of recurrences.

Direct Oral Anticoagulants or Standard Anticoagulant Therapy in Fragile Patients with Venous Thromboembolism.

Background The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance levels ≤ 50 mL/min and/or body weight ≤ 50kg) with venous thromboembolism (VTE) has not been evaluated. 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 DOACs or standard anticoagulant therapy. Results From January 2013 to April 2018, 24,701 patients were recruited. Of these, 10,054 (41%) were fragile. Initially, 473 fragile patients (4.7%) received DOACs and 8,577 (85%) low-molecular-weight heparin (LMWH). For long-term therapy, 1,298 patients (13%) received DOACs and 5,038 (50%) vitamin K antagonists (VKAs). Overall, 95 patients developed VTE recurrences and 262 had major bleeding. Patients initially receiving DOACs had a lower rate of the composite outcome (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.08-0.88) than those on LMWH. Patients receiving DOACs for long-term therapy had a nonsignificantly lower rate of the composite outcome (HR: 0.70; 95% CI: 0.46-1.03) than those on VKAs. On multivariable analysis, patients initially receiving DOACs had a nonsignificantly lower risk for the composite outcome (HR: 0.36; 95% CI: 0.11-1.15) than those on LMWH, while those receiving DOACs for long-term therapy had a significantly lower risk (HR: 0.61; 95% CI: 0.41-0.92) than those on VKAs. Conclusions Our data suggest that the use of DOACs may be more effective and safe than standard therapy in fragile patients with VTE, a subgroup of patients where the risk for bleeding is particularly high.

Management and outcome of major bleeding in patients receiving vitamin K antagonists for venous thromboembolism.

BACKGROUND: The optimal management of major bleeding in patients receiving vitamin K antagonists (VKA) for venous thromboembolism (VTE) is unclear. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to assess the management and 30-day outcomes after major bleeding in patients receiving VKA for VTE. RESULTS: From January 2013 to December 2017, 267 of 18,416 patients (1.4%) receiving long-term VKA for VTE had a major bleeding (in the gastrointestinal tract 78, intracranial 72, hematoma 50, genitourinary 20, other 47). Overall, 151 patients (57%) received blood transfusion; 110 (41%) vitamin K; 37 (14%) fresh frozen plasma; 29 (11%) pro-haemostatic agents and 20 (7.5%) a vena cava filter. During the first 30 days, 59 patients (22%) died (41 died of bleeding) and 13 (4.9%) had a thrombosis. On multivariable analysis, patients with intracranial bleeding (hazard ratio [HR]: 4.58; 95%CI: 2.40-8.72) and those with renal insufficiency at baseline (HR: 2.73; 95%CI: 1.45-5.15) had an increased mortality risk, whereas those receiving vitamin K had a lower risk (HR: 0.47; 0.24-0.92). On the other hand, patients receiving fresh frozen plasma were at increased risk for thrombotic events (HR: 4.22; 95%CI: 1.25-14.3). CONCLUSIONS: Major bleeding in VTE patients receiving VKA carries a high mortality rate. Intracranial bleeding and renal insufficiency increased the risk. Fresh frozen plasma seems to increase this risk for recurrent VTE.

Raised Fibrinogen Levels and Outcome in Outpatients With Peripheral Artery Disease.

The influence of raised fibrinogen levels on outcome in stable outpatients with peripheral arterial disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) registry to compare ischemic events, major bleeding, and mortality in stable outpatients with PAD, according to their baseline plasma fibrinogen levels. Of 1363 outpatients with PAD recruited in FRENA, 558 (41%) had fibrinogen levels >450 mg/100 mL. Over 18 months, 43 patients presented with acute myocardial infarction, 37 had an ischemic stroke, 51 underwent limb amputation, 19 had major bleeding, and 90 died. Compared to patients with normal levels, those with raised fibrinogen levels had an over 2-fold higher rate of ischemic stroke (rate ratio [RR]: 2.30; 95% confidence interval [CI]: 1.19-4.59), limb amputation (RR: 2.58; 95% CI: 1.46-4.67), or death (RR: 2.27; 95% CI: 1.49-3.51) and an over 3-fold higher rate of major bleeding (RR: 3.90; 95% CI: 1.45-12.1). On multivariate analysis, patients with raised fibrinogen levels had an increased risk of developing subsequent ischemic events (hazard ratio [HR]: 1.61; 95% CI: 1.11-2.32) and major bleeding (HR: 3.42; 95% CI: 1.22-9.61). Stable outpatients with PAD and raised plasma fibrinogen levels had increased rates of subsequent ischemic events and major bleeding.

Gender differences in patients with venous thromboembolism and five common sites of cancer.

BACKGROUND: The outcome of cancer patients with venous thromboembolism (VTE) may differ according to gender. METHODS: We used the RIETE database to compare the rate of VTE recurrences, major bleeding and mortality in patients with lung, colorectal, pancreatic, hematologic or gastric cancer during the course of anticoagulation, according to gender. RESULTS: As of January 2016, 11,055 patients with active cancer were enrolled: 1,727 had lung cancer, 1,592 colorectal, 840 hematologic, 517 pancreatic and 459 had gastric cancer. Compared with men (N = 3,130), women (N = 2,005) were more likely to have colorectal, pancreatic or hematologic cancer, and less likely to have lung cancer. Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH), but women received higher daily doses per body weight. Then, 66% kept receiving LMWH for long-term therapy. During the course of anticoagulation, 302 patients developed recurrent VTE, 220 bled and 1,749 died. Compared with men, women had a similar rate of VTE recurrences or major bleeding, and a lower mortality (risk ratio [RR]: 0.90; 95% CI: 0.82-0.99). When separately comparing outcomes according to cancer site, women with lung cancer had a lower mortality (RR: 0.79; 95% CI: 0.70-0.92), those with colorectal cancer had a higher mortality (RR: 1.25; 95% CI: 1.02-1.54) and those with gastric cancer had a higher rate of VTE recurrences than men (RR: 2.47; 95% CI: 1.04-5.89). CONCLUSIONS: VTE women with lung, colorectal, pancreatic, haematological or gastric cancer experienced a similar outcome during the course of anticoagulant therapy than men with similar cancers.

Clinical Prognosis of Nonmassive Central and Noncentral Pulmonary Embolism: A Registry-Based Cohort Study.

BACKGROUND: Whether the localization of nonmassive pulmonary embolism (PE) is associated with the short-term and long-term prognosis of patients remains unknown. Our aim was to characterize associations of nonmassive PE localization with risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation. METHODS: Among participants of the Registro Informatizado de la Enfermedad ThromboEmbòlica (RIETE) registry with incident symptomatic nonmassive PE diagnosed by CT scan, we compared risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation between central PE (main pulmonary artery) and noncentral PE (more peripheral arteries) using Cox proportional hazard-adjusted models. RESULTS: Of the 6,674 participants, patients with central PE (40.5%) had age (mean 66 years), sex (46.9% male sex), and proportion of idiopathic (45.0%) and cancer-related (22.3%) PE that were similar to those of patients with noncentral PE. During anticoagulation (5,256.1 patient-years), the risk of recurrent VTE was similar between the two groups (2.5 vs 2.1 per 100 patient-years; adjusted hazard ratio [aHR], 1.32; 95% CI, 0.91-1.90), as were risks of major bleeding and mortality. After anticoagulation was discontinued (2,175.4 patient-years), participants with central PE had a borderline greater risk of recurrent VTE than did participants with noncentral PE (11.0 vs 8.0 per 100 patient-years; aHR, 1.34; 95% CI, 1.01-1.78) but not when restricted to participants after unprovoked PE (13.8 vs 11.9 per 100 patient-years; aHR, 1.15; 95% CI, 0.79-1.68; P = .48). Risks of major bleeding and mortality were similar. CONCLUSIONS: In nonmassive PE, central localization of PE is associated with greater risk of recurrent VTE after anticoagulation cessation. However, the low magnitude of this association and the absence of association after unprovoked PE suggest that the clinical relevance of this finding is limited and that the duration of anticoagulation should not be tailored to PE localization after nonmassive unprovoked PE.

Supervised versus non-supervised exercise in patients with recent myocardial infarction: A propensity analysis.

BACKGROUND: The influence of supervised versus non-supervised exercise training on outcome in patients with a recent myocardial infarction (MI) is controversial. DESIGN: Longitudinal observational study. METHODS: FRENA is an ongoing registry of stable outpatients with symptomatic coronary, cerebrovascular or peripheral artery disease. We compared the rate of subsequent ischaemic events (MI, ischaemic stroke or lower limb amputation) and the mortality rate in patients with recent MI, according to the use of supervised versus non-supervised exercise training. The influence of physical activity on outcomes was estimated by using propensity score method in multivariate analysis. RESULTS: As of February 2014, 1124 outpatients with recent MI were recruited, of whom 593 (53%) participated in a supervised exercise training programme. Over a mean follow-up of 15 months, 25 patients (3.3%) developed 26 subsequent ischaemic events - 24 MI, one stroke, one lower-limb amputation - and 12 (1.6%) died. The mortality rate (0.15 vs. 2.89 deaths per 100 patient-years; rate ratio = 0.05; 95% confidence interval, 0.01-0.39) was significantly lower in supervised exercise than in non-supervised exercise patients. On propensity score analysis, the rate of the composite outcome was significantly lower in supervised exercise patients (1.80 vs. 6.51 events per 100 patient-years; rate ratio = 0.28; 95% confidence interval, 0.12-0.64). CONCLUSIONS: The use of supervised exercise training in patients with recent MI was associated with a significant decrease in the composite outcome of subsequent ischaemic events and death.

Anemia and Outcome in Outpatients With Peripheral Artery Disease.

The influence of anemia on outcome in stable outpatients with peripheral artery disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) Registry to compare ischemic events and mortality rates in stable outpatients with symptomatic PAD and anemia. Of 1663 patients with PAD, 208 (12.5%) had anemia. Over 18 months, patients with anemia had a higher rate of myocardial infarction (MI; rate ratio [RR]: 2.10; 95% confidence interval [CI]: 1.04-3.99), limb amputation (RR: 2.98; 95%CI: 1.70-5.05), and higher mortality (RR: 3.58; 95%CI: 2.39-5.28) than those without anemia. The rates of ischemic stroke (RR: 0.75; 95%CI: 0.23-1.93) and major bleeding (RR: 0.93; 95%CI: 0.15-3.51) were similar. On multivariable analysis, anemia was associated with an increased risk to die (hazard ratio [HR]: 2.32; 95%CI: 1.53-3.50) but not to develop MI (HR: 1.49; 95%CI: 0.73-3.05) or to have limb amputation (HR: 1.49; 95%CI: 0.86-2.59). In stable outpatients with PAD, anemia was associated with increased mortality but not with an increased rate of subsequent ischemic events or major bleeding.

[Indications and diagnosis efficiency of lumbar puncture in emergencies]. / Indicaciones y rendimiento diagnóstico de la punción lumbar en urgencias.

BACKGROUND: To know the frequency, indications and diagnosis efficiency of lumbar puncture (LP) in the Emergency Department (ED) when suspecting a central nervous system (CNS) infection. PATIENTS AND METHOD: We analyzed all the LP performed over a 2-year period in the ED. We compared the clinical characteristics of patients with and without CNS infection. We also reviewed all the cases of CNS infection diagnosed in the hospital in the same period. RESULTS: A LP was performed in 0.4% of emergencies. In 76% of cases, it was performed because of CNS infection suspicion, which was confirmed in 30% of cases. Fever, headache, nuchal rigidity and chronical otitis were all clinical variables associated with CNS infection. An 80% of CNS infections that were not diagnosed in the ED corresponded to HIV-infected patients. CONCLUSIONS: Lumbar puncture is frequently performed in the ED, mostly for suspicion of CNS infection, which is eventually confirmed in one third of cases. CNS infection cases which have not been suspected in the ED usually correspond to a subacute meningitis in a HIV-infected patient.

Predictors of outcome in stable outpatients with peripheral artery disease.

Patients with peripheral artery disease (PAD) are at increased risk for subsequent ischemic events. We used data from the FRENA Registry to find predictors of subsequent myocardial infarction (MI), ischemic stroke, and limb amputation in stable outpatients with PAD. As of January 2012, 1,270 patients with PAD were recruited, of whom 1,042 (82 %) had Fontaine stage II; 113 (8.9 %) stage III; and 115 (9.1 %) stage IV. Over a mean follow-up of 14 months, 35 patients developed MI, 25 had stroke, 39 underwent limb amputation, and 91 died. Among patients with Fontaine stage II, the incidence of MI (2.09 events per 100 patient-years; 95 % CI 1.43-2.97) or stroke (0.93; 95 % CI 0.52-1.56) was similar to that of limb amputation (3.22; 95 % CI 2.37-4.29). On multivariate analysis, patients with diabetes [hazard ratio (HR) 2.09; 95 % CI 1.05-4.18], prior coronary disease (HR 5.35; 95 % CI 2.24-12.8), or atrial fibrillation (HR 3.11; 95 % CI 1.52-6.37) were at increased risk for MI; female (HR 2.94; 95 % CI 1.32-6.67), those with prior stroke (HR 5.21; 95 % CI 1.22-22.2) or atrial fibrillation (HR 3.37; 95 % CI 1.45-7.85) at increased risk for stroke; and female (HR 2.38; 95 % CI 1.23-4.55), those with diabetes (HR 3.50; 95 % CI 1.58-7.73) or advanced stages of PAD were at increased risk for limb amputation. Prior coronary artery disease, diabetes and atrial fibrillation predicted subsequent MI; female gender, prior stroke and atrial fibrillation predicted stroke; and female gender, diabetes, and advanced stages of PAD predicted limb amputation.

Thirty-day mortality rate in women with cancer and venous thromboembolism. Findings from the RIETE Registry.

The influence of the site of cancer on outcome in cancer women with venous thromboembolism (VTE) is poorly understood. Reliable information on its influence might facilitate better use of prevention strategies. We assessed the 30-day outcome in all women with active cancer in the RIETE Registry, trying to identify if differences exist according to the tumor site. Up to May 2010, 2474 women with cancer and acute VTE had been enrolled. The most common sites were the breast (26%), colon (13%), uterus (9.3%), and haematologic (8.6%) cancers. During the 30-day study period, 329 (13%) patients died. Of them, 71 (2.9%) died of pulmonary embolism (PE), 22 (0.9%) died of bleeding. Fatal PE was more common in women with breast, colorectal, lung or pancreatic cancer (59% of the fatal PEs). Fatal bleeding was more frequent in women with colorectal, haematologic, ovarian cancer or carcinoma of unknown origin (55% of fatal bleedings).

Indicaciones y rendimiento diagnóstico de la punción lumbar en urgencias / Indications and diagnosis efficiency of lumbar puncture in the Emergency Department

FUNDAMENTO: Conocer la frecuencia con que se realiza la punción lumbar (PL) en urgencias y sus indicaciones, así como su rendimiento diagnóstico en la sospecha de infección del sistema nervioso central (ISNC). PACIENTES Y MÉTODO: Se analizaron las punciones practicadas durante dos años en un servicio de urgencias, comparando las características clínicas de los casos en que la PL confirmó o no la sospecha de infección. Se revisaron los casos de ISNC no sospechados en urgencias. RESULTADOS: En el 0,4 por ciento de las urgencias médicas se practicó un PL. En el 76 por ciento la indicación fue sospecha de ISNC, de las cuales se confirmaron el 30 por ciento. Fiebre, cefalea, rigidez de nuca y antecedentes de otitis o sinusitis crónica fueron las variables asociadas a ISNC. Un 11 por ciento de las ISNC no se sospecharon en urgencias, y de ellas el 80 por ciento tenían el antecedente de infección por el VIH.CONCLUSIONES: La PL se realiza frecuentemente en urgencias, fundamentalmente por sospecha de ISNC, que se confirma en un tercio de los casos. La ISNC no sospechada en urgencias corresponde mayoritariamente a meningitis subagudas en pacientes con infección por el VIH (AU)