James D. Douketis

A COMPARISON OF THREE MONTHS OF ANTICOAGULATION WITH EXTENDED ANTICOAGULATION FOR A FIRST EPISODE OF IDIOPATHIC VENOUS THROMBOEMBOLISM

BACKGROUND Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. RESULTS A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09). CONCLUSIONS Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.

2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary].

Obesity is now reaching epidemic proportions in both developed and developing countries and is affecting not only adults but also children and adolescents. Over the last 20 years, obesity has become the most prevalent nutritional problem in the world, eclipsing undernutrition and infectious disease

The Perioperative Management of Antithrombotic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This article discusses the perioperative management of antithrombotic therapy and is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). The primary objectives of this article are the following: (1) to address the perioperative management of patients who are receiving vitamin K antagonists (VKAs) or antiplatelet drugs, such as aspirin and clopidogrel, and require an elective surgical or other invasive procedures; and (2) to address the perioperative use of bridging anticoagulation, typically with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). A secondary objective is to address the perioperative management of such patients who require urgent surgery. The recommendations in this article incorporate the grading system that is discussed in this supplement (Guyatt G et al, CHEST 2008; 133:123S-131S). Briefly, Grade 1 recommendations are considered strong and indicate that the benefits do (or do not) outweigh risks, burden, and costs, whereas Grade 2 recommendations are referred to as suggestions and imply that individual patient values may lead to different management choices. The key recommendations in this article include the following: in patients with a mechanical heart valve or atrial fibrillation or venous thromboembolism (VTE) at high risk for thromboembolism, we recommend bridging anticoagulation with therapeutic-dose subcutaneous (SC) LMWH or IV UFH over no bridging during temporary interruption of VKA therapy (Grade 1C); in patients with a mechanical heart valve or atrial fibrillation or VTE at moderate risk for thromboembolism, we suggest bridging anticoagulation with therapeutic-dose SC LMWH, therapeutic-dose IV UFH, or low-dose SC LMWH over no bridging during temporary interruption of VKA therapy (Grade 2C); in patients with a mechanical heart valve or atrial fibrillation or VTE at low risk for thromboembolism, we suggest low-dose SC LMWH or no bridging over bridging with therapeutic-dose SC LMWH or IV UFH (Grade 2C). In patients with a bare metal coronary stent who require surgery within 6 weeks of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C); in patients with a drug-eluting coronary stent who require surgery within 12 months of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C). In patients who are undergoing minor dental procedures and are receiving VKAs, we recommend continuing VKAs around the time of the procedure and co-administering an oral prohemostatic agent (Grade 1B); in patients who are undergoing minor dermatologic procedures and are receiving VKAs, we recommend continuing VKAs around the time of the procedure (Grade 1C); in patients who are undergoing cataract removal and are receiving VKAs, we recommend continuing VKAs around the time of the procedure (Grade 1C).

Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure. METHODS The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C). CONCLUSIONS Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes.

Systematic review of long-term weight loss studies in obese adults : clinical significance and applicability to clinical practice

BACKGROUND:Obesity is a common health problem that requires a long-term care approach. We systematically reviewed long-term (≥2 y) studies investigating dietary/lifestyle, pharmacologic, and surgical weight loss methods to assess (1) weight loss efficacy, defined by absolute weight loss and the proportion of subjects with ≥5% weight loss, (2) effects of weight loss on cardiovascular risk factors, and (3) applicability of findings from studies to everyday clinical practice.METHODS:The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials databases were searched for studies investigating the long-term efficacy of weight loss methods in overweight and obese adults. Data were extracted for (i) weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii) proportion of subjects with ≥5% weight loss at the end of follow-up, and (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting blood glucose, and systolic and diastolic blood pressure.RESULTS:Dietary/lifestyle therapy provides <5 kg weight loss after 2–4 y, pharmacologic therapy provides 5–10 kg weight loss after 1–2 y, and surgical therapy provides 25–75 kg weight loss after 2–4 y. Weight loss of ≥5% baseline weight is not consistently associated with improvements in cardiovascular risk factors and these benefits appear to be intervention specific and occur mainly in people with concomitant cardiovascular risk factors. Weight loss studies have methodologic limitations that restrict the applicability of findings to unselected obese people assessed in everyday clinical practice. These limitations include an inadequate study duration, large proportions of subjects lost to follow-up, a lack of an appropriate usual care group, and a lack of reporting of outcomes in high-risk subgroups.CONCLUSIONS:Dietary/lifestyle and pharmacologic weight loss interventions provide modest weight loss, and may improve markers of cardiovascular risk factors although these benefits occur mainly in patients with cardiovascular risks. Studies investigating weight loss have methodologic limitations that restrict the applicability of findings to obese patients assessed in clinical practice.

Meta-analysis: Anticoagulant Prophylaxis to Prevent Symptomatic Venous Thromboembolism in Hospitalized Medical Patients

Context Anticoagulant prophylaxis of venous thromboembolism in hospitalized patients is better established in surgical practice than in medical practice, in part because of the lack of convincing clinical trial evidence in hospitalized medical patients. Contributions The authors found 9 controlled, randomized trials of currently recommended unfractionated heparin or low-molecular-weight heparin prophylaxis regimens in hospitalized medical patients. Prophylaxis decreased the rate of pulmonary embolism, including fatal pulmonary emboli, by one halfa statistically significant reduction. Prophylaxis did not change other outcomes, including major bleeding. Caution Methods to identify good candidates for prophylaxis do not yet exist. Implications Anticoagulant prophylaxis substantially reduces the risk for venous thromboembolism in hospitalized medical patients. The Editors Prevention of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep venous thrombosis (DVT), is an important management issue in at-risk hospitalized medical patients. The Agency for Healthcare Research and Quality ranks prevention of VTE as the first priority out of 79 preventive initiatives that can improve patient safety in health care settings (1). Anticoagulant prophylaxis with unfractionated heparin or low-molecular-weight heparin has been described as an efficacious, safe, and cost-effective intervention to prevent DVT in medical patients (24). Furthermore, the American College of Chest Physicians Guidelines on Antithrombotic Therapy gives anticoagulant prophylaxis in medical patients a grade 1A recommendation (4). Despite these considerations, anticoagulant prophylaxis in at-risk hospitalized medical patients is administered to only 16% to 33% of such patients (57), whereas up to 90% of at-risk surgical patients receive prophylaxis (8, 9). One reason that may explain this apparent under utilization of anticoagulant prophylaxis in medical patients is a lack of evidence that such treatment prevents clinically important outcomes, such as PE, which has been shown in surgical patients (10). Individual randomized trials of anticoagulant prophylaxis in medical patients have been underpowered to show a reduction in PE and have assessed treatment effects on asymptomatic, venography-detected DVT, which is a less compelling outcome (1113). Therefore, we performed a meta-analysis of randomized, controlled trials of anticoagulant prophylaxis in medical patients, focusing on the effects of treatment on clinically important efficacy outcomes (any PE, fatal PE, symptomatic DVT, and all-cause mortality) and safety outcomes (major bleeding). The aim of our study was to determine the effects of treatment while patients were receiving anticoagulant prophylaxis and to assess to what extent, if any, these treatment effects were maintained after prophylaxis had been stopped. Methods Data Sources We attempted to identify all published and unpublished randomized, controlled trials, irrespective of language, that described anticoagulant prophylaxis in medical patients by using MEDLINE (1966 to September 2006, week 3), EMBASE (1980 to September 2006, week 3), and Cochrane Central Register of Controlled Trials (2006, Issue 3) databases. We show the search strategy in the Appendix Table. We supplemented the strategy by manually reviewing reference lists and by contacting content experts. Appendix Table. Literature Search Strategy* Study Selection Two reviewers independently performed study selection. Disagreements were resolved through discussion and by a third reviewer. We included a study if it was a randomized, controlled trial that compared treatment with a prophylactic dose of anticoagulant (unfractionated heparin, low-molecular-weight heparin, or fondaparinux) with no treatment (placebo or no intervention) in medical patients. Included studies also had to assess at least 1 of the following outcomes: symptomatic PE, symptomatic DVT, major bleeding, or all-cause mortality. We excluded studies that involved only patients with stroke, as this is a selected, high-risk subgroup (4), or if outcomes were not objectively confirmed. For trials that were published in more than 1 study, we extracted data from the most recent publication and used earlier publications to clarify data. To assess agreement between reviewers for study selection, we used the kappa statistic, which measures agreement beyond chance (14). A value greater than 0.6 is considered substantial agreement, and a value greater than 0.8 is considered almost perfect agreement (15). Study Data Extraction We extracted and presented data according to the QUORUM criteria (16). For each study, 2 reviewers, who were blinded to the identity of the study authors and journal in which the studies were published, independently extracted data on study design, patient characteristics, and anticoagulant prophylaxis. We extracted data on the following treatment efficacy outcomes: any PE (that is, symptomatic nonfatal and fatal PE), fatal PE, symptomatic DVT, and all-cause mortality. Data were also extracted on major bleeding (safety outcome). We only considered objectively documented and independently adjudicated outcomes. We accepted the reported definitions of major bleeding and did not attempt to reclassify these events. We defined major bleeding as that which required transfusion of 2 or more units of packed red blood cells, involved a critical site (for example, retroperitoneal), or was fatal. To determine the treatment effects of anticoagulant prophylaxis during the time patients were receiving prophylaxis, we extracted data on efficacy and safety outcomes during the on-treatment period. To determine whether the treatment effects of anticoagulant prophylaxis were maintained after prophylaxis had been stopped, we planned to extract data on efficacy outcomes during the entire on-treatment and after-treatment periods. If outcome data could not be identified for extraction, we contacted the study authors by e-mail to request these data. If a response was not received after 15 days, we sent a second e-mail and contacted the secondary authors. We resolved disagreements about study data extraction by consensus or by discussion with a third reviewer. Anticoagulant Regimens We assessed the following anticoagulant regimens that are currently recommended for the prevention of VTE: unfractionated heparin, 5000 IU 2 or 3 times daily; enoxaparin, 40 mg or 60 mg once daily; enoxaparin, 30 mg twice daily; nadroparin, 4000 IU or 6000 IU once daily; dalteparin, 5000 IU once daily; and fondaparinux, 2.5 mg once daily. We excluded anticoagulant regimens that are not recommended for clinical use (for example, enoxaparin, 20 mg once daily). Study Quality Assessment Two reviewers who were blinded to the identity of the study authors and the journals in which the studies were published independently assessed study quality. The reviewers evaluated study quality by considering methods used to generate the randomization sequence, methods of double-blinding, and the description of patient withdrawals and dropouts. Data Synthesis and Analyses Primary Analyses We determined pooled relative risks and 95% CIs for any symptomatic PE (which included fatal and nonfatal PE), fatal PE, symptomatic DVT, all-cause mortality, and major bleeding in patients who received anticoagulant prophylaxis or no prophylaxis. We planned separate analyses for treatment effects during prophylaxis and for treatment effects after prophylaxis had been stopped. For treatment effects that were statistically significant, we determined the absolute risk reduction and number-needed-to-treat for benefit (NNTB) to prevent an outcome. We pooled data by using the MantelHaenszel method (17), and we performed a fixed-effects model by using Review Manager, version 4.2.8 (RevMan, Cochrane Collaboration, Oxford, England). Because combining trials with extremely low or zero event rates can yield biased results, we repeated the analyses using StatXact software, version 7 (Cytel Software Corporation, Cambridge, Massachusetts), which provides exact fixed-effect point and interval estimates for the odds ratio (18). The appropriateness of pooling data across studies was assessed using the I2 test for heterogeneity, which measures the inconsistency across study results and describes the proportion of total variation in study estimates that is due to heterogeneity rather than sampling error (19). Sensitivity Analyses We repeated sensitivity analyses by using only studies that satisfied each item of our prespecified quality evaluation (20). We created funnel plots of effect size versus standard error to assess for publication bias (21). Role of the Funding Source We received no financial support for this review. Results Study Identification and Selection We identified 830 potentially relevant studies from the following databases: 382 from MEDLINE, 358 from EMBASE, and 375 from the Cochrane Library (Figure 1). We excluded 813 studies after screening their title and abstract by using the predefined inclusion and exclusion criteria and retrieved the remaining 17 studies for more detailed evaluation (2238). We identified another 3 studies by manual review of references of retrieved articles (3941). Through contact with content experts, we identified 2 other studies (42, 43). Of the 22 retrieved studies, 13 were excluded for the following reasons: 4 because they had duplicate data (24, 29, 31, 34); 4 because they did not have an untreated control group (25, 27, 30, 36); 2 because they did not contain original data (26, 28); 1 because it included medical and surgical patients (37); 1 because it was not properly randomized (40); and 1 because it identified the control group arbitrarily and not by randomization (39). Therefore, we included 9 studies in our systematic review (22, 23, 32, 33, 35, 38, 4143). We had excellent interobserver agreement for study selection (= 0.98). Tabl

Perioperative Bridging Anticoagulation in Patients With Atrial Fibrillation

BACKGROUND It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial.

Background— Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. Methods and Results— The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients received dabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P=0.34. Procedures included: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the last dose of study drug was given 49 (35–85) hours before the procedure on comparison with 114 (87–144) hours in patients receiving warfarin, P<0.001. There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran 110 mg (3.8%) or dabigatran 150 mg (5.1%) or warfarin (4.6%); dabigatran 110 mg versus warfarin: relative risk, 0.83; 95% CI, 0.59 to 1.17; P=0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95% CI, 0.80 to 1.49; P=0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110 mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to 1.41; P=0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P=0.44. Conclusions— Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.Background —Dabigatran reduces ischemic stroke compared to warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. Methods and Results —The current analysis was undertaken to compare the peri-procedural bleeding risk of patients in the RE-LY trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days prior until 30 days following invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least one invasive procedure: 24.7% of patients receiving dabigatran-110; 25.4% on dabigatran-150 and 25.9% on warfarin, p=0.34. Procedures included: pacemaker/ defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%) and joint replacement (6.2%). Among patients assigned to either dabigatran dose the last dose of study drug was given 49 (35-85) hours prior to the procedure; compared to 114 (87-144) hours in patients receiving warfarin, p<0.001. There was no significant difference in the rates of peri-procedural major bleeding between patients receiving dabigatran-110 (3.8%) or dabigatran-150 (5.1%) or warfarin (4.6%); dabigatran-110 vs. warfarin: RR=0.83, 95% CI: 0.59-1.17, p=0.28; dabigatran-150 vs. warfarin: RR=1.09, 95% CI: 0.80-1.49, p=0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran-110, 17.7% with dabigatran-150 and 21.6% with warfarin: dabigatran-110: RR=0.82, 95% CI: 0.48-1.41, p=0.47; dabigatran-150: RR=0.82, 95% CI: 0.50-1.35, p=0.44. Conclusions —Dabigatran and warfarin were associated with similar rates of peri-procedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. Clinical Trial Registration Information —clinicaltrials.gov; Identifier: [NCT00262600][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00262600&atom=%2Fcirculationaha%2Fearly%2F2012%2F06%2F11%2FCIRCULATIONAHA.111.090464.atom

Single-Arm Study of Bridging Therapy With Low-Molecular-Weight Heparin for Patients at Risk of Arterial Embolism Who Require Temporary Interruption of Warfarin

Background—When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital. Methods and Results—This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths. Conclusions—Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists: Systematic Review and Meta-Analysis of Bleeding and Thromboembolic Rates

Background— Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. Methods and Results— MEDLINE, EMBASE, and Cochrane databases (2001–2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (&kgr;=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0–3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0–1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42–1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00–9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52–8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04–2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27–4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non–vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. Conclusions— Vitamin K antagonist–treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging.Background— Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. Methods and Results— MEDLINE, EMBASE, and Cochrane databases (2001–2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (κ=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0–3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0–1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42–1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00–9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52–8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04–2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27–4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non–vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. Conclusions— Vitamin K antagonist–treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging. # Clinical Perspective {#article-title-50}