Molecular clues to venous thromboembolism recurrence.

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

To explore the risk factors of venous thromboembolism (VTE) recurrence and the predictive value of simplified pulmonary embolism severity index (sPESI) in medical inpatients. A total of 149 consecutive patients with first diagnosed VTE from the medical departments of West China Hospital of Sichuan University from January 2011 and December 2012 were enrolled and followed-up for 24 months. The VTE recurrence rate was calculated and univariate and multivariate cox proportional hazards regression analysis were performed to identify the risk factors associated with VTE recurrence. All the patients were evaluated by sPESI, and survival analysis was used to explore its value in predicting VTE recurrence in these medical patients. Out of the included 149 patients, 23(15.4%) patients had VTE recurrence during the 2 years' follow-up and median recurrence time was 167 days. The univariate analysis showed bed rest, severe lung disease, nephrotic syndrome, inappropriate anticoagulant therapy, smoking, diabetes, and malignant neoplasm might be associated with VTE recurrence (P=0.043, 0.006, 0.009, 0.032, 0.098, 0.048, 0.021). Among these risk factors, the multivariate analysis revealed severe lung disease, nephrotic syndrome, and malignant neoplasm were the independent risk factors (HR=3.45, 5.67, 3.60; P=0.020, 0.020, 0.047); while for inappropriate anticoagulant therapy, the P value was marginal (HR=3.94, 95% CI: 0.99-15.63, P=0.051). The median sPESI scores of the patients with VTE recurrence was higher than that of the patients without VTE recurrence[1(1, 2) vs 0(0, 1), P=0.001], and patients with sPESI≥1 were associated with 5.57-fold increased risk of VTE recurrence compared with patients with sPESI=0 (95%CI: 1.79-17.30, P=0.001). Survival analysis also showed that the 2-year cumulative VTE recurrence rate of patients with sPESI≥1 was significant higher than that of patients with sPESI=0 (38.4% vs 5.7%, P=0.001). The medical VTE patients have high VTE recurrence risk, and severe lung disease, nephrotic syndrome, malignant neoplasm and inappropriate anticoagulant therapy are important risk factors of VTE recurrence. The sPESI has predictive value for VTE recurrence in medical patients.

Venous Thromboembolism (VTE) Recurrence in Patients with Recurrent/Metastatic Solid Cancer Receiving Anticoagulation Therapy After Index VTE; Findings From Korean VTE Registry,

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, or mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding, and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65 years with acute VTE were followed for 2 years, starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding, and mortality. Thrombin generation was assessed in 551 patients 1 year after the index VTE. At this time, 59% of the patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12–14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28–3.73) in the presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identify among elderly patients those at higher risk of VTE recurrence.

Background: Renal impairment could be a risk factor for venous thromboembolism (VTE) recurrence and anticoagulation related bleeding in VTE patients. The objective of this study was to assess the effect of renal impairment on the risk of VTE recurrence, major bleeding and total health care costs in patients with acute VTE. Methods: In this retrospective analysis of IMS PharMetrics Plus TM claims database, patients (≥18 years old) who had ≥ 1 inpatient or ≥ 2 outpatient VTE claims during January 2010-December 2013 (the index period) were identified. Patients who had continuous enrollment eligibility for at least 12 months before (baseline) and 12 months after (follow-up) the index date (first VTE claim) and had no VTE diagnosis and anticoagulant treatment during baseline period were included. Patients who required dialysis or had end stage renal disease were excluded. VTE patients with chronic kidney disease (stage I-IV or equivalent) during baseline based on ICD- 9 diagnosis codes were compared with those without renal impairment. Recurrent VTE was identified by inpatient or emergency department claims associated with VTE diagnosis after hospital discharge of the index VTE event or 7 days after index date for patients with index VTE events treated in the outpatient setting during the follow-up period. Major bleeding events were identified by inpatient claims with a bleeding diagnosis that occurred after an anticoagulant prescription fill among patients receiving anticoagulant therapy. Cox proportional hazards models adjusted for age, gender, index VTE type, health insurance type, outpatient anticoagulant therapy use, and baseline comorbidities was used to assess the risk of VTE recurrence and anticoagulation related major bleeding. Generalized linear model with gamma distribution and log link was used to evaluate the total health care costs (inclusive of medical and pharmacy costs) over the 1-year follow-up period adjusting for the same baseline characteristics. Results: Of 20,873 eligible VTE patients (median age 57 years; 50% female), 238 had diagnosed renal impairment. Compared with patients without renal impairment, patients with renal impairment had higher rates for VTE recurrence (24% vs. 18%; adjusted hazard ratio (HR) = 1.32, 95% CI 1.06-1.63, p<0.01), and post anticoagulation major bleeding (4% vs 1%; HR=1.75, 95% CI 1.01-3.03, p=0.046). Patients with renal impairment had higher adjusted mean total health care costs ($41,283 vs. $30,757, p<0.01) than patients without renal impairment. Conclusion: VTE patients with renal impairment had higher risk for VTE recurrence and major bleeding associated with anticoagulant therapy, resulting in increased utilization of health care resources than VTE patients without renal impairment. Sponsorship: This research was funded by Daiichi Sankyo Inc, Parsippany, NJ.

Association between initial and residual pulmonary vascular obstruction and pulmonary embolism recurrence, a pooled analysis

Introduction: This study estimated venous thromboembolism (VTE) recurrence and risk factors in a European population, given limited data in this region. Methods: This retrospective cohort study included data collected from physicians recruited from an online panel in France, Spain, Italy, and Germany. Physicians completed case report forms for the next 3-4 patients seen in consultation for any reason who had an initial VTE event in the prior 3 to 24 months (i.e., patients who survived 90 days since their initial VTE). Included were 376 general practitioners and 307 specialists, providing 2,184 patient records and information on patient demographics, comorbidities, and VTE recurrence. Kaplan-Meier estimation provided cumulative incidence survival functions accounting for censored data (patient records varied from 3-24 months post-initial VTE). Risk factors for VTE were assessed. Results: Patients’ mean age was 61.3 years (SD=14.3) and 47.4% were female. Of 2,184 patients, 379 developed recurrent VTE over 1,298 person-years of follow-up. The table shows cumulative incidence of VTE in the overall population and by risk categories. The 6-month cumulative incidence of VTE recurrence was 11.7%; the 12-month cumulative incidence was 27.6%. VTE cumulative incidence did not differ by age, gender or initial VTE type. However, it was higher in patients with moderate-to-strong vs. weak Anderson & Spencer summary risk scores (p=.001); e.g., 12-month rates of 33.8%, vs. 20.9%, respectively. Conclusions: VTE recurrence is high in this European population and increases with time since initial VTE event, suggesting the need for targeted anticoagulant treatment following an initial VTE event and longer term prevention of VTE recurrence. Among risk factors investigated, Anderson & Spencer scores help differentiate patients more likely to experience recurrence within 12 months of initial VTE.

Background: Non-O blood type patients are at higher risk of first venous thromboembolic event compared to others. However, only little is known about ABO blood type and risk of venous thromboembolism (VTE) recurrence. In this study, we sought to determine the impact of ABO blood type on VTE recurrence. Methods and results: We prospectively recruited 130 consecutive patients with a first episode of pulmonary embolism (PE) (CT scan-documented). Patients lost to follow-up within 12 months after anticoagulation therapy discontinuation were excluded from the study. We finally analysed prospective data from 100 patients with extensive follow-up. Mean follow-up was 35 months [33.3-36.7]. PE was unprovoked in 48 patients (48%) and mean anticoagulation duration was 5.3±2.2 months. The rate of recurrence was 10.2% per patient and per year (31 recurrences, 31%). B blood type patients had a 2.6-fold increased risk of developing VTE recurrence (95% CI 1.1-6.1, p=0.04). In a bivariate COX model, B blood type remained a strong predictor of VTE recurrence (HR 2.7, 95% CI 1.1-6.2, p=0.02). A and AB blood types were not associated with VTE recurrence. Non-O blood type patients tended to relapse more frequently than O patients (HR 2.1, 95% CI 0.8-5.0, p=0.09). Interestingly, in women, non-O blood type was associated with a 4.9-fold increase in VTE recurrence (95% CI 1.1-21.4, p=0.01). VTE recurrence rate and B blood type VTE recurrence rate and B blood type Conclusion: Non-O blood types, beyond being involved in occurrence of VTE, contribute to the risk of VTE recurrence. B blood type is strongly associated with VTE recurrence, and can identify patients at high risk who could benefit from long-term anticoagulation therapy after a first VTE event.

Fixed-dose low-molecular-weight heparin, bemiparin, in the long-term treatment of venous thromboembolism in patients with transient risk factors in standard clinical practice: the FLEBUS study.

Impact of Interim Hospitalizations on Risk of Venous Thromboembolism (VTE) Recurrence: A Nested Case-Cohort Study

The modified Ottawa score (MOS) predicted venous thromboembolism (VTE) recurrence in a cohort of patients with cancer-associated thrombosis mainly managed on an outpatient basis. We aimed to assess the prognostic value of the MOS in hospitalized patients with cancer-associated thrombosis. In 383 hospitalized patients with cancer-associated VTE from the SWIss VTE Registry, 98 (25%) were classified as low risk, 175 (46%) as intermediate risk, and 110 (29%) as high risk for VTE recurrence based on the MOS. Clinical end points were recurrent VTE, fatal VTE, major bleeding, and overall mortality at 90 days. Overall, 179 (47%) patients were female, 172 (45%) had metastatic disease, and 72 (19%) prior VTE. The primary site of cancer was lung in 48 (13%) patients and breast in 43 (11%). According to the MOS, the rate of VTE recurrence was 4.1% for low, 6.3% intermediate, and 5.5% high risk (p = 0.75); the rate of fatal VTE was 0.8, 1.9, and 2.0% (p = 0.69); the rate of major bleeding was 3.1, 4.1, and 3.6% (p = 0.92); and the rate of death was 6.1, 12.0, and 28.2% (p < 0.001), respectively. None of the MOS items was associated with VTE recurrence: female gender hazard ratio (HR) 1.26 (95% confidence interval [CI], 0.53–2.96), lung cancer HR 1.17 (95% CI, 0.35–3.98), prior VTE HR 0.44 (95% CI, 0.10–1.91), breast cancer HR 0.83 (95% CI, 0.19–3.58), and absence of metastases HR 0.74 (95% CI, 0.31–1.74). In hospitalized patients with cancer-associated VTE, the MOS failed to predict VTE recurrence at 3 months but was associated with early mortality.

Intensity of Heparin Anticoagulation as an Independent Predictor of 14-Day Recurrence after Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.

The incidence and risk factors of recurrent venous thromboembolism during pregnancy

The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant. We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding. Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%). During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].).

Healthcare Resource Utilization and Costs Associated with Venous Thromboembolism Recurrence in Patients with Cancer