Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

Warfarin and antiplatelet combination use among commercially insured patients enrolled in an anticoagulation management service

BACKGROUND: Although warfarin and antiplatelet medications have documented efficacy for prevention of primary and secondary cardiovascular events, the appropriateness of warfarin and antiplatelet combination therapy is not well described in national consensus guidelines. METHODS AND RESULTS: Cross-sectional data from 4,557 Kaiser Permanente Colorado members > or = 18 years old who were receiving warfarin anticoagulation therapy were used to quantify the prevalence of warfarin and antiplatelet agent (ie, aspirin, clopidogrel, dipyridamole, and/or dipyridamole/aspirin) combination therapy as of September 30, 2005, and to identify characteristics of patients receiving combination therapy. The prevalence of warfarin and any antiplatelet combination therapy was 385/1,000 (95% confidence interval [CI], 371/1,000 to 399/1,000). The majority of combination therapy was warfarin and aspirin (prevalence, 378/1,000) with a daily dose of aspirin, 81 mg, being the most reported dose (prevalence, 328/1,000). Patients receiving combination therapy were more likely to be male (63.6% vs 46.4%; adjusted odds ratio, 1.5; 95% CI, 1.3 to 1.7) and have a comorbidity of heart failure (29.0% vs 15.6%; adjusted odds ratio, 1.2; 95% CI, 1.1 to 1.5), coronary artery disease (62.4% vs 17.5%; adjusted odds ratio, 7.6; 95% CI, 6.5 to 8.8), and/or stroke/transient ischemic attack (5.2% vs 1.6%; adjusted odds ratio, 3.5; 95% CI, 2.3 to 5.3). CONCLUSION: Nearly 4 of 10 patients receiving warfarin management care were receiving warfarin and antiplatelet combination therapy. The findings suggest that this practice is widespread, especially among patients with established cardiovascular disease, and involves a substantially higher number of patients than previously reported. The clinical outcomes associated with this practice require further investigation.     

Recognition, treatment, and prevention of heparin-induced thrombocytopenia: review and update

Heparin-induced thrombocytopenia (HIT) is one of the most important life- and limb-threatening adverse drug events encountered by physicians. Serious sequelae associated with HIT can be avoided with early recognition and appropriate treatment. This review examines the recommendations published in 2004 by the American College of Chest Physicians on the recognition, treatment, and prevention of HIT together with more recent data, especially regarding treatment with direct thrombin inhibitors.     

Use of the Delphi method to facilitate antithrombotics prescription during pregnancy

Introduction

Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis.

Materials and Methods

A Delphi exercise was conducted to collect 19 French experts’ opinions on pregnancy-related VTE.

Results

Experts with an active interest in clinical research and care of VTE and placental vascular complications were selected. The risk score was classified by an anonymous computer vote. A scoring system for VTE risk in pregnant women was developed, each score being associated with a specific treatment: graduated elastic compression stockings, aspirin, prophylactic Low Molecular Weight Heparin (LMWH: variable durations), or adjusted-dose of LMWH through pregnancy and postpartum.

Conclusions

Our simple consensual scoring system offers an individual estimation of thrombosis risk during pregnancy together with its related therapeutic strategy, in accordance with most of the new international recommendations. The accuracy of our individual risk score-based therapeutic guidance is currently being prospectively evaluated in a multicenter trial (Clinicaltrials.gov registry no: NCT00745212).     

Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate,activated prothrombin complex concentrate and recombinant activated factor VII in vitro

Introduction

Anticoagulation therapies carry a risk of bleeding; reversal agents may be beneficial in cases of severe bleeding even for anticoagulants with a relatively short half-life, such as the oral factor Xa inhibitor rivaroxaban.

Materials and Methods

We investigated the in vitro reversal effect of prothrombin complex concentrate (PCC; 0.2-1.0 U/mL), activated PCC (aPCC; 0.2–1.0 U/mL) and recombinant activated factor VII (rFVIIa; 5–50 μg/mL) on rivaroxaban-induced (200–1000 ng/mL) changes in prothrombin time (PT) and thrombin generation (TG) in plasma, and in thromboelastometry (clotting time [CT]) in whole blood from healthy subjects.

Results

All three agents were partially effective in reversing rivaroxaban-induced anticoagulation but showed different profiles. rFVIIa and aPCC were more effective than PCC in reversing prolongations of PT, CT and TG lag time; rFVIIa was more effective than aPCC. However, the reversal effect reached a plateau with a maximal effect of approximately 50%. Inhibition of maximum thrombin concentration was slightly reversed by these agents; aPCC was the most effective. In contrast, inhibition of endogenous thrombin potential (ETP) was strongly reversed by aPCC, with significant increases over baseline at low rivaroxaban concentrations. Compared with aPCC, PCC showed a similar but less effective reversal profile. rFVIIa reversed ETP inhibition by approximately 50%.

Conclusions

The extent of reversal by aPCC, PCC and rFVIIa was dependent on the parameter measured in rivaroxaban-anticoagulated plasma or blood. ETP measurements may have predictive power for assessing the reversal potential of PCC or aPCC and may be used to indicate an increased prothrombotic risk.     

A systematic review on the effect of aspirin in the prevention of post-operative arterial thrombosis in patients undergoing total hip and total knee arthroplasty

Introduction

Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR).

Materials and Methods

Studies were identified by reviewing the reference of the ACCP guidelines and by electronic search of MEDLINE database from January 2012 to December 2013 and of the web database www.trialresultscenter.org.

Results

We analyzed 5 of the 78 studies that were identified by our search strategy; they included 5179 patients; the median follow-up was 90 days. The incidence of post-operative AT tended to be lower in ASA-treated patients, compared to anticoagulant-treated patients, although the difference did not reach statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence of post-operative VTE tended to be higher in ASA-treated patients, compared to anticoagulant-treated patients (1.48, 95% CI 0.93-2.36).

Conclusions

Due to the heterogeneity and low quality of the studies, which do not allow firm conclusions, it is uncertain whether aspirin is effective in reducing the incidence of postoperative AT. Our results do emphasize the need for developing specifically designed studies to test the safety and efficacy of ASA in the prevention of post-operative AT.     

A general Critical Care Ultrasonography workshop: results of a novel Web-based learning program combined with simulation-based hands-on training

Purpose

The aim of this study was to facilitate attainment of Critical Care Ultrasonography (CCUS) competence.

Materials and Methods

We developed a Web-based learning program followed by simulation-based hands-on training in noncardiac CCUS for novice learners. We administered knowledge and skills tests before and after the workshop and conducted surveys on confidence levels using a 10-point Likert scale. Knowledge tests were conducted online, and skills tests were video-captured for evaluation.

Results

Sixteen physicians participated in a 4-hour combined vascular and thoracic CCUS workshop, and 23 in a 2-hour abdominal CCUS workshop. In the combined vascular and thoracic workshop, the mean (SD) pre-workshop and post-workshop knowledge scores were 24 (4) and 33 (5), respectively, out of 43 (P < .001). The pre-workshop and post-workshop skill scores were 15 (5) and 23 (2), out of 28 (P < .001). In the abdominal workshop, the pre-workshop and post-workshop knowledge scores were 11 (3) and 18 (2), out of 20 (P < .001). The pre-workshop and post-workshop skill scores were 6 (3) and 15 (2), out of 16 (P < .001). Learners' confidence increased significantly in both workshops (P < .001).

Conclusions

Our novel hybrid educational workshop on general CCUS significantly improved knowledge, skills, and confidence levels. Our flexibly scheduled module can be a practical option for the busy intensivist.     

Benefits and risks of oral anticoagulation for stroke prevention in nonvalvular atrial fibrillation

Nonvalvular atrial fibrillation is the most common clinically significant cardiac arrhythmia in the United States. It increases both the risk for and the severity of strokes and is associated with substantial morbidity, mortality, decreased quality of life, and related health care costs. Guidelines recommend anticoagulation therapy for the majority of patients with atrial fibrillation. Clinical trials have established that vitamin K antagonists are effective for stroke prevention for patients with atrial fibrillation for whom anticoagulation is recommended. However, vitamin K antagonists remain underutilized for a variety of reasons, including drug, physician, and patient factors. While vitamin K antagonists considerably reduce the risk of stroke, the absolute risk reduction varies according to individual patient risk factors. Accurately assessing each patient's true risk of stroke and bleeding is essential when determining which (if any) antithrombotic strategy should be used. Several stroke risk stratification schemes exist; of these, CHADS₂ is widely employed and simple. New, more sophisticated schemes may generate more precise risk estimates and better identify those patients for whom anticoagulant therapy offers a net clinical benefit. More studies are needed to determine the utility of bleeding risk stratification systems, as well as the role of surgical and interventional alternatives to anticoagulation treatment. Several novel oral anticoagulants are in (or have completed) phase 3 clinical trials. Dabigatran etexilate, approved in the United States in October 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, now offers the first oral alternative to warfarin for patients with atrial fibrillation.