Risk of recurrence after a first unprovoked venous thromboembolism : external validation of the Vienna Prediction Model with pooled individual patient data

Background: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Patients/Methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P\ua0=\ua00.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12\ua0months. Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence

Perioperative management of antiplatelet therapy in patients with a coronary stent who need noncardiac surgery : a systematic review of clinical practice guidelines

Background: It is unclear how to appropriately manage discontinuation and resumption of antiplatelet therapy in patients with coronary stents who need noncardiac surgery. We undertook a systematic review of the literature to identify practice guideline statements regarding antiplatelet therapy in patients with coronary stents undergoing noncardiac surgery. Methods: We used six search strategies to identify practice guideline statements that comment on perioperative antiplatelet management for patients with coronary stents undergoing noncardiac surgery. Two independent reviewers assessed study eligibility, abstracted data, and completed quality assessment. Results: We identified 11 practice guidelines that met the eligibility criteria; these were included in the review. These guidelines advised that elective noncardiac surgery be delayed for at least 4 weeks after bare-metal stent implantation and at least 6 months after drug-eluting stent implantation. For elective surgery, all guidelines advised continuing acetylsalicylic acid (ASA) therapy whenever possible. If interruption of antiplatelet therapy was required, four guidelines advised to discontinue ASA/clopidogrel at least 5 days before surgery, while two guidelines advised to discontinue 7 to 10 days before surgery. Five guidelines provided varying guidance for the use of perioperative bridging during antiplatelet therapy interruption. Conclusions: Most current recommendations are based on expert opinion. This review highlights the need for well-designed prospective studies to identify optimal management strategies in patients with coronary stents who are on antiplatelet therapy and who need noncardiac surgery

Managing new oral anticoagulants in the perioperative and intensive care unit setting

Managing patients in the perioperative setting receiving novel oral anticoagulation agents for thromboprophylaxis or stroke prevention with atrial fibrillation is an important consideration for clinicians. The novel oral anticoagulation agents include direct Factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran. In elective surgery, discontinuing their use is important, but renal function must also be considered because elimination is highly dependent on renal elimination. If bleeding occurs in patients who have received these agents, common principles of bleeding management as with any anticoagulant (including the known principles for warfarin) should be considered. This review summarizes the available data regarding the management of bleeding with novel oral anticoagulation agents. Hemodialysis is a therapeutic option for dabigatran-related bleeding, while in vitro studies showed that prothrombin complex concentrates are reported to be useful for rivaroxaban-related bleeding. Additional clinical studies are needed to determine the best method for reversal of the novel oral anticoagulation agents when bleeding occurs. Copyright © 2013, the American Society of Anesthesiologists, Inc.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Patient-level compared with study-level meta-analyses demonstrate consistency of D-dimer as predictor of venous thromboembolic recurrences

Objective: We compared the performance of aggregate data (AD)–based and individual patient data (IPD)–based meta-analyses to synthesize evidence on the ability of D-dimer to distinguish recurrence risk in patients with unprovoked venous thromboembolism (VTE) who stopped anticoagulation. Study Design and Setting: We compared the results of the published AD-based rate ratio of VTE recurrence for positive vs. negative D-dimer, estimated by a mixed-effect Poisson model, with those of the IPD-based hazard ratio obtained by a Cox regression stratified by trial. We performed three additional analyses to investigate the methodological reasons for differences between the two approaches, comparing the IPD Cox regression with AD generated from IPD Poisson regression (to control for differences in population on study), AD time-to-event meta-analysis, and AD generated from IPD meta-regression. Results: Published analyses agreed in direction and statistical significance when estimating the prognostic value of D-dimer even if IPD estimates suggested a stronger effect. The additional analyses suggested that differences in study populations might explain this slight difference. Poor reporting in published studies precluded a true comparison of AD- and IPD-based assessments of heterogeneity sources. Conclusion: AD and IPD meta-analyses yielded similar estimates of D-dimer effect to distinguish risk for recurrent VTE. The IPD approach was justified by the need to investigate sources of heterogeneity.</p

Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis A patient-level meta-analysis

Residual venous obstruction (RVO) could improve the stratification of the risk of recurrence after unprovoked deep vein thrombosis (DVT), but results from clinical studies and study-level meta-analyses are 1 conflicting. It was the objective of this analysis to determine if RVO is a valid predictor of recurrent venous thromboembolism (VTE) in patients with a first unprovoked DVT who had received at least three months of anticoagulant therapy. Individual patient data were obtained from the datasets of original studies, after a systematic search of electronic databases (Medline, Embase, Cochrane Library), supplemented by manual reviewing of the reference lists and contacting content experts. A multivariate, shared-frailty Cox model was used to, calculate hazard ratios (HRs) for recurrent VIE, including, as covariates: RVO; age; sex; anticoagulation duration before RVO assessment; and anticoagulation continuation after RVO assessment. A total of 2,527 patients from 10 prospective studies were included. RVO was found in 1,380 patients (55.1%) after a median of six months from a first unprovoked DVT. Recurrent VIE occurred in 399 patients (15.8%) during a median follow-up of 23.3 months. After multivariate Cox analysis, RVO was independently associated with recurrent VIE (HR = 1.32, 95% confidence interval [CI]: 1.06-1.65). The association was stronger if RVO was detected early, i.e. at three months after DVT (HR = 2.17; 95% Cl: 1.11-4.25), but non-significant if detected later, i.e. >6 months (HR = 1.19; 95% Cl: 0.87-1.61). In conclusion, after a first unprovoked DVT, RVO is a weak overall predictor of recurrent VIE. The association is stronger if RVO is detected at an earlier time (3 months) after thrombosis