Low-dose Unfractionated Heparin Research Articles

Incidence of thrombotic and bleeding complications during cardiac catheterization in children: comparison of high‐dose vs. low‐dose heparin protocols

During cardiac catheterization (CC) in children, unfractionated heparin (UFH) is used for primary prophylaxis of thrombotic events (TE). However, the optimal UFH dose to minimize TE and bleeding in children has yet to be established. To (i) objectively assess the incidence of TE and bleeding during pediatric CC using clinical assessment and ultrasound; and (ii) compare a high-dose vs. low-dose UFH protocol for thromboprophylaxis. A randomized controlled trial (RCT) comparing high-dose UFH (100 units kg(-1) bolus, followed by 20 units kg h(-1) continuous infusion) vs. low-dose UFH (50 units kg(-1) bolus) during CC. Outcome assessment was by clinical examination and vascular ultrasound, performed by blinded examiners before and within 48 h after CC. Children with no consent for randomization were followed in a cohort receiving standard-of-care UFH (parallel-cohort RCT). A total of 227 children were included; 137 were randomized and 90 followed in the cohort study. The overall incidence of TE was 4.6% and bleeding 6.6%. The RCT was stopped early for futility as there were no differences between the high-dose and the low-dose UFH in TE (5% vs. 3%; risk ratios [RR] 1.5, 95% confidence interval [CI] 0.3; 9) and bleeding (7% vs. 12%, RR 0.6, 95% CI 0.2; 2). There were also no differences when RCT and cohort study populations were combined. The incidences of TE and bleeding during CC in children were low. There were no differences between the high-dose and the low-dose UFH protocols studied. Although Heparin Anticoagulation Randomized Trial in Cardiac Catheterization (HEARTCAT) was not designed as non-inferiority trial, low-dose UFH (50 units kg(-1) bolus) appears sufficient for thromboprophylaxis during CC.

Pharmacologic Prophylaxis for Venous Thromboembolism Among Hospitalized Patients with Acute Medical Illness: An Electronic Medical Records Study

Abstract 2074 Introduction:Patients hospitalized with acute medical illness have an elevated risk of venous thromboembolism (VTE). ACCP guidelines list various risk factors including active cancer, congestive heart failure (CHF), respiratory failure, chronic obstructive pulmonary disease (COPD), sepsis, advanced age, history of VTE and immobility. These guidelines also recommend prophylactic anticoagulation using fondaparinux, low molecular-weight heparin, or low-dose unfractionated heparin. This study examined pharmacologic prophylaxis against VTE among hospitalized medically ill patients and assessed demographic and clinical correlates related to VTE prophylaxis. Methods:A retrospective observational study was conducted with electronic medical records (EMR) in a large Midwestern U.S. public hospital and its network of outpatient clinics between 1999 and 2010. Patients >=40 years old were included if they were hospitalized with a primary diagnosis (ICD-9 code) of CHF, pneumonia, cancer, stroke, infectious diseases, sepsis, severe respiratory disorders (including COPD, asthma, and acute respiratory failure), inflammatory bowel disease (IBD), or neurologic disorders, or were hospitalized for VTE within the year before the index admission. Each patient’s first qualifying hospitalization during the 12-year period was included in the analysis. Patients were excluded if the length of stay was <3 days, the primary diagnosis was VTE, if a hospital diagnosis of VTE was given in the past 30 days, or if IV heparin or a treatment dose of subcutaneous (SC) heparin (>15,000 units/day) or enoxaparin (>40 mg/day) was started within one day of admission. Patients treated with warfarin (and not heparin or enoxaparin) were also excluded. Fondaparinux was not on the formulary. Prophylaxis was defined as present if the first dose (during the hospital stay) of anticoagulation with SC heparin or enoxaparin was lower than the treatment dose levels defined above. All IV heparin was considered to be at treatment-level doses. SC heparin records with missing doses were considered to be at prophylaxis-level doses. Logistic regression was used to examine factors associated with VTE prophylaxis. Results:Of 13,029 patients eligible for the study, mean age was 58.6 years; 51% were women; 47% were white, 47% African-American, 6% other; 58% had public healthcare coverage, 15% commercial insurance, 27% self-pay. Among patients with a BMI stored in the EMR, 44% were obese, 23% overweight, and 28% normal. There was a history of cigarette smoking in 44% and atrial fibrillation in 8%. The primary hospital diagnoses were infectious diseases 21.2%, cancer 19.9%, severe respiratory disorders 14.5%, pneumonia 12.7%, CHF 12.2%, stroke 9.6%, sepsis 8.9%, IBD <1%, neurologic disorders <1%, and other <1%. Mean length of stay was 7.8 days (median 5 days).The overall prophylaxis rate was 22.1% (14.8% for 1999–2002, 22.0% for 2003–2006, 28.5% for 2007–2010), including 11.8% with enoxaparin and 10.3% with SC heparin. Multivariable logistic regression showed that VTE prophylaxis was significantly associated with year of hospitalization (OR=2.2 for ‘07-'10, OR=1.7 for ‘03-'06 vs. ‘99-'02, P<.001), SC heparin in the 30 days before admission (OR=1.6, p=0.02), aspirin use (OR=1.4, p<.0001), a primary hospital diagnosis of sepsis (OR=1.4, p<.0001), self-pay status (OR=1.2 vs. commercial insurance, p=0.01), and age (for 10 year increments, OR=1.07, p=0.001). The following factors were associated with reduced likelihood of VTE prophylaxis: smoking (OR=0.9, p=.005), alcohol use (OR=0.9, p=.04), warfarin in the past 30 days (OR=0.5, p=0.02), and a primary diagnosis of stroke (OR=0.7, p<0.0001), infectious disease (OR=0.7, p<.0001), or IBD (OR=0.3, p=.003). Conclusion:Pharmacologic VTE prophylaxis has increased significantly over the past 12 years but is still largely underused in patients hospitalized with acute medical illness. Multiple demographic, behavioral and clinical factors are associated with VTE prophylaxis during hospitalization. Further research is needed to examine if VTE prophylaxis is associated with reduced VTE risk and healthcare utilization. Disclosures:Rosenman:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding. Liu:Pfizer: Employment. Phatak:Bristol-Myers Squibb: Employment. Qi:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Teal:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Nisi:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Liu:Pfizer: Employment, Equity Ownership. Ramacciotti:Bristol-Myers Squibb: Employment.

Preventing deep vein thrombosis after stroke: strategies and recommendations.

Opinion statementThe risk of deep vein thrombosis (DVT) after stroke is increased in patients with restricted mobility, a previous history of DVT, dehydration, or comorbidities such as malignant diseases or clotting disorders. Patients with an increased risk of DVT should receive prophylactic treatment. To reduce the chance of DVT, patients should be mobilized as soon as possible and should be kept well hydrated. Anti-embolism stockings cannot be recommended, because they have been demonstrated not useful for preventing DVT or pulmonary embolism in patients with stroke, and they are associated with a significantly increased risk of skin breaks. The usefulness of intermittent pneumatic compression is currently under study in a randomized clinical trial. Treatment with subcutaneously administered low-dose unfractionated heparin is preferred to unfractionated heparin and may be considered in patients with ischemic stroke if the risk of DVT is estimated to be higher than the risk of hemorrhagic complications. Aspirin may also be effective for patients with ischemic stroke who have contraindications to anticoagulants, although direct comparisons with anticoagulants are not available. In patients with intracerebral hemorrhage, low-dose subcutaneous low-molecular-weight heparin is probably safe after documentation of cessation of active bleeding, and may be considered on an individual basis after 3 to 4 days from stroke onset.

Dosing Frequency of Unfractionated Heparin Thromboprophylaxis: A Meta-analysis

In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid. This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied. Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes. Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.

Deep vein thrombosis after total knee or hip arthroplasty is associated with increased preoperative calf muscle deoxygenation as measured by near-infrared spectroscopy

To assess whether the preoperative level of deoxygenated hemoglobin (HHb) in the calf muscle during light-intensity exercise is useful for identifying patients at risk of developing deep vein thrombosis (DVT) after total knee or hip arthroplasty. Sixty-eight patients undergoing total knee or total hip arthroplasty were enrolled. The Caprini risk assessment model was used to stratify patients into Caprini 5 to 6, Caprini 7 to 8, and Caprini >8 groups. The preoperative diameter of each venous segment was measured, and the time-averaged velocity (TAV) and time-averaged flow (TAF) of the popliteal vein (POPV) were assessed. Moreover, the prevalence of venous reflux in the POPV was evaluated preoperatively. Near-infrared spectroscopy (NIRS) was used to measure the calf muscle HHb level. The calf venous blood filling index (FI-HHb) was calculated on standing, and then the calf venous ejection index (EI-HHb) was obtained after one tiptoe movement and the venous retention index (RI-HHb) after 10 tiptoe movements. All patients received low-dose unfractionated heparin preoperatively and fondaparinux for postoperative thromboprophylaxis. Patients with arterial insufficiency, those who had preoperative DVT, and those who developed bilateral DVT after surgery were excluded from the study. Four patients were excluded on the basis of the exclusion criteria. Among the 64 patients evaluated, 14 (21.9%) were found to have DVT postoperatively. Among the risk factors for DVT, only the previous DVT was significantly predominant in patients who developed DVT (P = .001). The diameter of the popliteal vein was significantly smaller in patients who developed postoperative DVT than in those who did not (P = .001). Similarly, the diameter of the gastrocnemius vein was significantly larger in patients with postoperative DVT than in those without (P = .010). TAV and TAF were significantly increased in the popliteal vein in patients who developed postoperative DVT (P = .043, 0.046, respectively). Both groups showed a similar prevalence of reflux in the POPV (P = .841). The preoperative NIRS-derived RI was significantly increased in patients who developed DVT relative to those who did not (P = .004). The RI increased as the Caprini score progressed; however, there were no statistically significant differences between the three categories. Using ultrasound- and NIRS-derived parameters of significance as a unit of analysis, an optimal RI cut-off point of >2.3 showed the strongest ability to predict postoperative DVT, followed by a cut-off point >0.25 cm for the diameter of the gastrocnemius vein (GV). NIRS-derived RI >2.3 may be a promising parameter for identifying patients at risk of developing postoperative DVT despite pharmacologic DVT prophylaxis. A GV diameter of >0.25 cm also seems to contribute to the development of postoperative DVT. These results might be helpful to physicians for deciding which patients require more intensive thromboprophylaxis.

Venous thromboembolism following colorectal surgery for suspected or confirmed malignancy.

Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery between 2005 and 2009 for colorectal cancer. Low-dose unfractionated heparin (LDUH) was used in 52.7% of patients, low-molecular-weight heparin (LMWH) in 35.3%, and 10.7% received LDUH followed by LMWH. Pharmacological prophylaxis was continued after hospitalisation in 31.6%. Major bleeding occurred in 4% of patients. The 30-day mortality rate was 1.9%. The incidence of symptomatic VTE from hospital admission for surgery to 12 months after was 2.4%. There were no in-hospital VTE events. The majority of events occurred in the three-month period after discharge, but there were VTE events up to 12 months, especially in patients with more advanced cancer and multiple comorbidities.

Preventing Postsurgical Venous Thromboembolism: Pharmacological Approaches

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Venous Thromboembolism Prophylaxis in Patients Undergoing Cranial Neurosurgery: A Systematic Review and Meta-analysis

Randomized clinical trials (RCTs) have usually supported using heparin prophylaxis against venous thromboembolism (VTE) in patients undergoing cranial neurosurgery. The tradeoff between benefit and bleeding risk, however, has not been adequately characterized. To conduct a systematic review and meta-analysis assessing the extent to which low-dose unfractionated heparin (LDUH) or low-molecular-weight heparin (LMWH) prophylaxis reduces the rate of VTE and increases the rate of intracerebral hemorrhage (ICH) and other bleeding in patients undergoing elective cranial neurosurgery. We selected RCTs that evaluated LDUH or LMWH prophylaxis of VTE in patients undergoing elective cranial neurosurgery. A meta-analysis assessing heparins vs no heparin (either with or without mechanical methods) was performed. Eight RCTs were identified. Six RCTs involving 1170 patients evaluated LDUH or LMWH vs a control group. Five of 6 trials found a significant reduction in the risk of symptomatic and asymptomatic VTE with heparin prophylaxis. The pooled risk ratio was 0.58 (95% confidence interval, 0.45-0.75). ICH was more common in those receiving heparin, but not statistically significantly. For every 1000 patients who receive heparin prophylaxis, 91 VTE events will be prevented (approximately 35 of which are proximal deep vein thrombosis or pulmonary embolism and 9 to 18 of which are symptomatic), whereas 7 ICHs and 28 more minor bleeds will occur. Heparin prophylaxis for patients undergoing elective cranial neurosurgery reduces the risk of VTE but may also increase bleeding risks with a ratio of serious or symptomatic VTE relative to serious bleeding that is only slightly favorable.

Pharmacological Deep Vein Thrombosis Prophylaxis Does Not Lead to Hematoma Expansion in Intracerebral Hemorrhage With Intraventricular Extension

Patients with intracerebral hemorrhage (ICH) are at high risk for development of deep venous thrombosis. Current guidelines state that low-dose subcutaneous low molecular weight heparin or unfractionated heparin may be considered at 3 to 4 days from onset. However, insufficient data exist on hematoma volume in patients with ICH before and after pharmacological deep venous thrombosis prophylaxis, leaving physicians with uncertainty regarding the safety of this practice. We identified patients from our stroke registry (June 2003 to December 2007) who presented with ICH only or ICH+intraventricular hemorrhage and received either low molecular weight heparin subcutaneously or unfractionated heparin within 7 days of admission and had a repeat CT scan performed within 4 days of starting deep venous thrombosis prophylaxis. We calculated the change in hematoma volume from the admission and posttreatment CTs. Hematoma volume was calculated using the ABC/2 method and intraventricular hemorrhage volumes were calculated using a published method of hand drawn regions of interest. We identified 73 patients with a mean age of 63 years and median National Institutes of Health Stroke Scale score 11.5. The mean baseline total hematoma volume was 25.8 mL±23.2 mL. There was an absolute change in hematoma volume from pre- and posttreatment CT of -4.3 mL±11.0 mL. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological deep venous thrombosis prophylaxis within 2 or 4 days after ICH found no increase in hematoma size. Pharmacological deep venous thrombosis prophylaxis given subcutaneously in patients with ICH and/or intraventricular hemorrhage in the subacute period is generally not associated with hematoma growth.

Venous Thromboembolism Risk Assessment and Prophylaxis: A Comprehensive Systematic Review of the Facilitators and Barriers to Healthcare Worker Compliance with Clinical Practice Guidelines in the acute care setting.

Review question/objective The objective of this review is to identify, appraise and synthesise the best available evidence on the facilitators and barriers to compliance with Venous Thromboembolism (VTE) risk assessment and prophylaxis clinical practice guidelines in the acute care setting. More specifically, the review question is: To what extent are clinical practice guidelines for risk assessment and prophylaxis of VTE adhered to in the acute care setting, and what are the facilitators and barriers? Inclusion criteria Types of participants This review will consider any studies that include all health care professionals regardless of their designated involvement with venous thromboembolism risk assessment and prophylaxis in the acute care setting. Phenomena of interest This review will consider studies that evaluated the facilitators and barriers to venous thromboembolism compliance with clinical practice guidelines in the acute care setting. The qualitative component of the review will consider as phenomena of interest any studies that identify facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The quantitative component of the review will consider any studies that report on the barriers and facilitators to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The textual component of the review will consider any paper that discusses the facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. Types of outcomes This review will consider studies that include measures of compliance as their outcome measures. The qualitative component of the review will consider any studies that identify facilitators and/or barriers to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The quantitative component of the review will consider any studies that report on the barriers and facilitators to compliance with clinical practice guidelines in relation to venous thromboembolism risk assessment and prophylaxis in the acute care setting. The textual component of the review will consider any paper TRUNCATED AT 350 WORDS

Venous Thromboembolism Risk Assessment and Prophylaxis: A Comprehensive Systematic Review of the Facilitators and Barriers to Healthcare Worker Compliance with Clinical Practice Guidelines in the acute care setting.

Venous Thromboembolism Risk Assessment and Prophylaxis: A Comprehensive Systematic Review of the Facilitators and Barriers to Healthcare Worker Compliance with Clinical Practice Guidelines in the acute care setting.

The new oral anticoagulants, do they change the benefit vs. risk for thromboprophylaxis in association to ambulatory surgery?

Several randomized controlled trials have shown that pharmacological thromboprophylaxis with low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux reduces venous thromboembolism (VTE) after general surgery. No high-quality evidence supports the use of pharmacological thromboprohylaxis with traditional antithrombotic drugs in patients undergoing ambulatory surgery without additional VTE risk factors, stratified at low risk of VTE by the American College of Chest Physicians guidelines. Two new drug classes, the direct thrombin and factor Xa (FXa) inhibitors, have been developed with a potentially better risk-benefit profile. Oral administration, predictable anticoagulant responses, low potential for drug-drug interactions render direct thrombin and factor Xa inhibitors good candidates to replace UFH, LMWH and fondaparinux for VTE prophylaxis. Most of all, the positive results of the first published clinical trials in orthopedic thromboprophylaxis allowed dabigatran etexilate and rivaroxaban to be licensed in Canada and in European Union for the prevention of VTE in patients undergoing hip-replacement and knee-replacement surgery. No randomized trials with the new anticoagulants are ongoing in ambulatory surgery. However, currently available drugs--that is UFH, LMWH or fondaparinux--are administered subcutaneously and the new anticoagulants would offer the clear advantage of an oral administration, without request for blood testing to monitor potential adverse effects such as heparin-induced thrombocytopenia, thus potentially simplifying the treatment out of the hospital.

PCV48 ST. VINCENT'S PRIVATE HOSPITAL VENOUS THROMBOEMBOLISM PREVENTION PROJECT: ANALYSIS OF REDUCED COST AND IMPROVED CLINICAL OUTCOMES

OBJECTIVES : Prophylaxis with a low molecular weight heparin (LMWH) such as enoxaparin or a low-dose unfractionated heparin (LDUH) in high risk medical and surgical patients is consistent with the recommendations made by the American College of Chest Physicians Eighth Conference on Antithrombotic and Thrombolytic Therapy. While these guidelines present strong evidence to support the use of prophylaxis to prevent venous thromboembolism (VTE), they are not always adhered to in clinical practice. The St. Vincent’s Private Hospital VTE Prevention Project aimed to improve compliance with best practice prophylaxis in hospitalized patients. An audit of the rates of prophylaxis was conducted over a 12-month period as part of this project. The aim of this analysis was to determine whether the measures implemented as a result of the St. Vincent’s project translated into cost savings and improved clinical outcomes. METHODS : A decision-analytic model was constructed using audit data from 21,942 medical and surgical patients admitted to St. Vincent’s who received either enoxaparin 40 mg daily, unfractionated heparin (UFH) three times daily (TID) or no prophylaxis. The rate of prophylaxis at baseline was compared with that at the end of the audit for each prophylaxis regimen. Clinical trial data was used to estimate the incidence of VTE (defi ned as deep vein thrombosis [DVT] and pulmonary embolism [PE]), and major bleeding. RESULTS : As a result of the measures introduced to improve adherence to best practice, we estimated 13 fewer deaths, 84 fewer symptomatic DVTs, 19 fewer symptomatic PEs and 512 fewer hospital bed days over baseline, across all medical and surgical patients. We also estimated that overall costs were reduced by $245,439 over 12 months. CONCLUSIONS : Improved adherence to best practice in VTE prophylaxis in the Australian clinical setting is likely to result in fewer deaths, VTE events and signifi cant overall cost savings.

Choosing the Right Heparin Prophylaxis Strategy in Medical Patients at Risk for Developing VTE: An Evidence-Based Approach

Many acutely ill medical patients are at significant risk for developing venous thromboembolism (VTE) during hospitalization. Venous thromboembolism risk arises from both the presenting clinical condition as well as predisposing risk factors, such as advanced age. Thromboprophylaxis is underprescribed in these patients. Thrombotic risk assessment could encourage the prescribing of thromboprophylaxis and, therefore, improve patient protection against VTE. Current guidelines from the American College of Chest Physicians and the International Union of Angiology (IUA) recommend thromboprophylaxis with low-dose unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH), or fondaparinux for acutely ill medical patients with VTE risk factors. However, the optimal dose regimen for UFH is unclear. The 2006 evidence-based guidelines from the IUA recommend a 3-times-daily dose regimen for UFH. However, UFH is usually administered twice daily despite a lack of evidence for the superiority of this regimen. Both heparin-induced thrombocytopenia and bleeding are associated with UFH, and to a lesser degree with alternative anticoagulants, such as the LMWHs. If utilized, an appropriate prophylaxis regimen in medical patients can reduce the risk of VTE and its burden.

An open-label comparison of the efficacy and safety of certoparin versus unfractionated heparin for the prevention of thromboembolic complications in acutely ill medical patients: CERTAIN

Objective: Guidelines recommend low-dose unfractionated heparin (UFH) and low-molecular-weight heparin for the prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients. We report the findings of an open-label, active-controlled, multicenter study in acutely ill medical patients comparing certoparin and UFH.Research design and methods: Open-label, active-controlled, multicenter study. Patients received certoparin 3000 IU daily or UFH 7500 IU twice daily.Main outcome measures: The primary endpoint was a composite of symptomatic or asymptomatic proximal or distal deep vein thrombosis, symptomatic pulmonary embolism, or VTE-related death.Results: 172 patients were randomized to UFH and 163 to certoparin for 8.5 ± 2.1 days. The incidence of the primary endpoint was 18.0% in patients receiving UFH and 10.7% with certoparin [absolute difference -7.3; 95% confidence interval (CI) -16.9 to 2.3; p = 0.1353]. The incidence during follow-up was 2.6% in the UFH and 2.0% in the certoparin group (absolute difference -0.6; 95%CI -4.0 to 2.8; p = 0.7150). Major bleeding events occurred in three patients with UFH and one patient with certoparin.Conclusions: In acutely ill medical patients of at least 40 years of age, thromboprophylaxis with certoparin 3000 IU daily is effective and safe in comparison with 7500 IU twice daily UFH.

Should Patients With Stroke Wear Compression Stockings to Prevent Venous Thromboembolism?

In this issue, the CLOTS Trial Collaboration presents findings from CLOTS Trial 2, which compared thigh-length stockings with below-knee stockings in 3014 patients with acute stroke and found fewer...

Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux: The FUTURA/OASIS-8 Randomized Trial

The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain. To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010. Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT). Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30. The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group and 0.1% in the standard-dose group, P = .15). Low-dose compared with standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and vascular access-site complications. clinicaltrials.gov Identifier: NCT00790907.

Low-Molecular-Weight Heparin Versus Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Medicine Patients—A Pharmacoeconomic Analysis

Prevention of in-hospital venous thromboembolism (VTE) is identified internationally as a priority to improve patient safety. Advocated alternatives include low-dose unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Although LMWHs are as effective as UFH, less frequent administration and potentially safer adverse effect profile associated with LMWHs might off-set greater drug acquisition costs. The objective of this study was to determine the most cost-effective thromboprophylaxis strategy for hospitalized medicine patients and specific subgroups in Canada. A decision-analytic model assessed costs and outcomes of LMWH compared to UFH for thromboprophylaxis in at-risk hospitalized medicine patients from an institutional perspective. The outcome of interest was the incremental cost-effectiveness ratio (ICER) for preventing deep vein thrombosis (DVT) and combined untoward events (pulmonary embolism [PE], major bleed, and death). The time horizon of the model was the hospital stay. In the base-case analysis, LMWH thromboprophylaxis resulted in higher costs ($7.40), but 3.6 and 1.1 fewer DVT and untoward events per 1000 patients, respectively, with associated ICERs of $2042 and $6832. Results remained predominantly stable when alternative assumptions were evaluated in the sensitivity analysis. Low-molecular-weight heparin had the most favorable economic profile in patients with a history of DVT. In the probabilistic sensitivity analysis, in 33% of simulations LMWH was less costly and more effective, whereas the reverse was true for UFH only in 13% of simulations. Low-molecular-weight heparin administration is a cost-effective alternative for thromboprophylaxis strategy in Canadian hospitalized medicine patients.

Venous Thromboembolic Disease in Congestive Heart Failure

Congestive heart failure (CHF) is a medical condition associated with a relatively high risk of venous thromboembolism (VTE). Without thromboprophylaxis, venographically proven deep vein thrombosis occurs in 10% to 22% of hospitalized patients with CHF. Although the elevated VTE risk associated with CHF has been attributed to a variety of abnormalities in the context of Virchow's triad, newer information suggests that an associated chronic inflammatory state may be culpable. Both traditional VTE risk factors and cardiac-specific risk factors further increase the risk of VTE in patients with CHF. Severe left ventricular dysfunction, clinical instability (New York Heart Association class III-IV), young age, and/or right ventricular dysfunction appear to enhance the VTE risk associated with CHF. Grade IA pharmacologic thromboprophylactic recommendations for the hospitalized CHF patient include low molecular weight-heparin, fondaparinux, and low-dose unfractionated heparin. Regrettably, a variance in societal guidelines on the importance of VTE in hospitalized CHF patients may lead to underutilization of thromboprophylaxis.

Incidence of pulmonary thromboembolism in gastric cancer surgery using routine thromboprophylaxis

There is a lack of published data on the incidence of pulmonary thromboembolism (PTE) after resections for gastric cancer. We report the incidence of PTE after gastric cancer surgery with routine thromboprophylaxis from a high-volume center. Between October 2002 and December 2008, 3262 patients underwent gastric cancer surgery with routine thromboprophylaxis using low-dose unfractionated heparin, intermittent pneumatic compression, fluid infusion, and graduated compression stockings. Patients diagnosed with PTE were identified from a prospectively collected database that included complications related to thromboprophylaxis. Seven patients (0.2%) developed symptomatic PTE in this series. Multivariate analysis demonstrated that female sex (P = 0.029) and high body mass index (P = 0.025) were significant risk factors for PTE. The most common symptom was dyspnea (57%). Five patients (71%) developed PTE by the second postoperative day. All patients were treated successfully with medical treatment and no hospital deaths were recorded. Adverse events related to thromboprophylaxis included major postoperative bleeding in 10 (0.3%) of the 3262 patients. There were no cases of hematoma related to the insertion of epidural catheters for analgesia. The routine use of thromboprophylaxis in Japanese patients undergoing gastric resection is safe and effective in reducing the incidence of pulmonary thromboembolism.