Effectiveness and Safety of Rivaroxaban Versus Warfarin in Frail Patients with Venous Thromboembolism

Purpose

Frailty predicts poorer outcomes in patients receiving anticoagulation. We assessed the effectiveness and safety of rivaroxaban vs warfarin in frail patients experiencing venous thromboembolism.

新型口服抗凝药物与维生素K拮抗剂相关的脑出血风险对比

新型口服抗凝药物是血栓预防和治疗的一个重要组成部分,它能有效地用于非瓣膜性心房颤动患者的卒中预防、深静脉血栓的预防与治疗等,但其仍有引起出血并发症的风险。目前的研究表明,新型口服抗凝药物相关的脑出血风险比维生素K拮抗剂相关的脑出血风险更低;新型口服抗凝药物治疗心房颤动合并脑出血的患者时,缺血性卒中和复发性脑出血的风险与华法林相比无显著降低;新型口服抗凝药物相关的脑出血的血肿特征和功能预后与维生素K拮抗剂相比无显著差异,甚至血肿体积更小,预后更好。     

Comparison of Sodium and Calcium Heparin in Prevention of Venous Thromboembolism

Abstract: Comparison of sodium and calcium heparin in prevention of venous thromboembolism. J. F. Cade, J. T. Andrews and A. E. Stubbs. Aust. HZ. J. Med., 1982, 12 , pp. 501–504.
The relative efficacy of sodium and calcium heparin in preventing venous thromboembolism and their relative side-effects were studied in 234 high-risk patients in a randomised, double-blind, placebo-controlled trial. The two heparin preparations were from the same batch and in the same concentration, and were given in a dose of 5000 U 12 hourly. Positive leg scans were found in 19% after placebo, 12% after sodium heparin and 8% after calcium heparin. Bruising at the injection site was more common after calcium heparin (66%) than after sodium heparin (53%) or placebo (38%). Pain at the injection site was also more common after calcium heparin (26%) than after sodium heparin (8%) or \ placebo (6%). Changes in the activated partial thromboplastin time were small and did not correlate with leg scan results or bruising. While there was a tendency for calcium heparin to be possibly more effective, it was followed by significantly more local haema toma and pain.     

Venous Thromboembolism: A Review of Risk and Prevention in Colorectal Surgery Patients

Hospitalization for surgery has a high risk of developing venous thromboembolism, a condition that encompasses both deep-vein thrombosis and its potentially fatal complication, pulmonary embolism. Colorectal surgery implies a specific high risk for postoperative thromboembolic complications relative to other general surgery. This may be a result of pelvic dissection, the perioperative positioning of these patients, or the presence of additional risk factors common to this patient group, such as cancer, advanced age, or inflammatory bowel disease. The potential impact of venous thromboembolism and the need for effective thromboprophylaxis often are underestimated in these patients. Recommendations for thromboprophylaxis in colorectal surgery patients are based on the American College of Chest Physicians guidelines for thrombosis prevention in general surgery patients, with treatment stratified according to the type of surgery and additional venous thromboembolism risk factors present. Prophylaxis with low-molecular-weight heparin or unfractionated heparin is recommended for colorectal surgery patients classified as moderate to high risk. The small number of studies focusing specifically on colorectal patients, or on cancer or abdominal surgery patients with a colorectal subgroup, has shown that both low-molecular-weight heparin and unfractionated heparin can effectively reduce the incidence of venous thromboembolism. Low-molecular-weight heparin has the practical advantage of once-daily administration and shows a lower risk of heparin-induced thrombocytopenia. This review will assess the risk of venous thromboembolism in colorectal surgery patients and discuss current evidence-based guidelines and recommendations for prevention of venous thromboembolism. Funded by Sanofi-Aventis, NJ. Reprints are not available.     

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin,in Experimentally Induced Colitis in Rat

Purpose Parenteral administration of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. Method Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005–0.9 mg), other LMWHs (0.3–0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. Results Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-γ expression. Conclusions CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNB-induced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis. An erratum to this article can be found at     

Haemostatic Activity in Patients with Atrial Fibrillation Treated with Low-Molecular-Weight Heparin Before and After Electrical Cardioversion

BACKGROUND: Electrical cardioversion of atrial fibrillation (AF) is associated with a thromboembolic risk, and this risk can be reduced by the use of antithrombotic therapy. International guidelines recommend an effective oral anticoagulant therapy (OAT) for at least 3 weeks before, and 4 weeks after cardioversion. We studied whether electrical cardioversion in it self causes changes in the level of activity in the haemostatic system during treatment with either low-molecular-weight heparin (LMWH). METHODS: Thirty-eight patients with AF were randomised consecutively to either LMWH administered subcutaneous in a fixed daily dose, or conventional OAT. Changes in the biochemical markers prothrombin fragment 1+2 (F1+2), D-Dimer, and soluble fibrin, all reflecting the activity in the haemostatic system, were assessed at baseline, before and after electrical cardioversion in patients treated with LMWH for 3 weeks prior to cardioversion. A follow up compared the time spent on anticoagulation prior to cardioversion, and eventual complications in the two group (LMWH vs. OAT). RESULTS AND CONCLUSIONS: No significant differences between the levels of the biochemical markers measured before, and after cardioversion were seen, indicating that during anticoagulant therapy with LMWH, electrical cardioversion in itself, does not cause an increased activity in the haemostatic system. Also the level of F1+2 had declined significantly after cardioversion, when compared to baseline level in patients, whom had a normal sinus rhythm (NSR) re-established. This indicates that even in patients on a stable anticoagulant treatment, restoration of a NSR can cause a further decrease in thrombin generation.The median time spent on antithrombotic treatment prior to cardioversion, was significantly different between the LMWH (27 days) and the OAT group (138 days). Our study indicates that cardioversion in patients on LMWH does not cause a hypercoagulable state and that LMWH significantly shortens the time spent on anticoagulant therapy prior to cardioversion.     

Dosing of Unfractionated Heparin in Obese Patients with Venous Thromboembolism

BACKGROUND  

Aggressive weight-based dosing guidelines help achieve prompt therapeutic anticoagulation in patients with venous thromboembolism (VTE). While obese patients with VTE face an increased risk of recurrence, physicians typically resist prescribing doses two to three times the usual dose because of concern about bleeding complications.     

Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism

Background

Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined.

Venous Thromboembolism Prophylaxis in the Medical Patient: Controversies and Perspectives

Despite the high morbidity and mortality associated with venous thromboembolism in hospitalized at-risk medical patients, the publication of large-scale studies showing that prophylaxis is effective in this patient group, and the presence of international guidelines, prophylaxis rates in medically ill patients remain suboptimal. Studies show that low-molecular-weight heparins, given once daily, are at least as effective as unfractionated heparin usually given thrice daily with equivalent or improved safety profiles, and that thrice-daily dosing of unfractionated heparin might be more effective than twice-daily dosing. However, the most recent American College of Chest Physicians guidelines do not distinguish between these regimens, and twice-daily unfractionated heparin is still commonly used in the United States. Furthermore, the optimal duration for out-of-hospital and extended prophylaxis for specific patient groups is not established. Finally, there are few data on the use of mechanical methods in this patient group and no established standard of care for prophylaxis of special patient populations, such as obese patients or those with renal insufficiency. Even though prophylaxis entails additional acquisition costs, it can reduce the incidence of venous thromboembolism, which can improve care and decrease overall costs.     

急性脑卒中患者静脉血栓栓塞症调查及危险因素探讨

<正>静脉血栓栓塞症(venous thromboembolism,VTE)包括深静脉血栓形成(deep venous thrombosis,DVT)和肺血栓栓塞症(pulmonary thromboembolism,PTE)。脑卒中患者是VTE发生的高危人群,如果不给予任何干预措施,30%~40%的脑卒中患者会发生DVT,严重     

Platelet Count and Major Bleeding in Patients Receiving Vitamin K Antagonists for Acute Venous Thromboembolism,Findings From Real World Clinical Practice

The outcome of patients with acute venous thromboembolism (VTE) and abnormal platelet count (PlC) at baseline has not been consistently studied. In real-world clinical practice, a number of patients with abnormal PlC receive vitamin K antagonists (VKAs) to treat acute VTE despite their higher risk of bleeding.We used the Registro Informatizado de Enfermedad TromboEmbólica registry database to compare the rate of major bleeding in patients receiving VKA for long-term therapy of acute VTE according to PlC levels at baseline. Patients were categorized as having very low (<100,000/μL), low (100,000–150,000/μL), normal (150,000–300,000/μL), high (300,000–450,000/μL), or very high (>450,000/μL) PlC at baseline.Of 55,369 patients recruited as of January 2015, 37,000 (67%) received long-term therapy with VKA. Of these, 611 patients (1.6%) had very low PlC, 4006 (10.8%) had low PlC, 25,598 (69%) had normal PlC, 5801 (15.6%) had high PlC, and 984 (2.6%) had very high PlC at baseline. During the course of VKA therapy (mean, 192 days), there were no differences in the duration or intensity (as measured by international normalized ratio levels) of treatment between subgroups. The rate of major bleeding was 3.6%, 2.1%, 1.9%, 2.1%, and 3.7%, respectively, and the rate of fatal bleeding was 0.98%, 0.17%, 0.29%, 0.34%, and 0.50%, respectively. Patients with very low or very high PlC levels were more likely to have severe comorbidities.We found a nonlinear “U-shaped” relationship between PlC at baseline and major bleeding during therapy with VKA for VTE. Consistent alteration of PlC values at baseline suggested a greater frailty.     

Rivaroxaban Versus Warfarin and Risk of Post-Thrombotic Syndrome Among Patients with Venous Thromboembolism

Background

The effectiveness of rivaroxaban to reduce post-thrombotic syndrome in patients with venous thromboembolism is largely unknown. We compared rates of post-thrombotic syndrome in patients given rivaroxaban versus warfarin in a cohort of patients with incident venous thromboembolism receiving routine clinical care.

Low-Molecular-Weight Heparin in the Initial Treatment of Proximal Deep Vein Thrombosis

Intravenous unfractionated heparin followed by oral warfarin is the current standard of care for the treatment of acute venous thrombosis. More recently, several low-molecular-weight heparin preparations have been shown to be as effective and safe as unfractionated heparin for the initial therapy of acute proximal vein thrombosis. These drugs have a number of advantages over unfractionated heparin, and will undoubtedly replace the current standard for the initial treatment of venous thromboembolism.     

辛伐他汀联合低分子肝素治疗不稳定型心绞痛的疗效观察

目的观察辛伐他汀联合低分子肝素治疗不稳定型心绞痛（UA）的疗效。方法选择2008年6月—2010年6月来我院就诊的不稳定心绞痛的患者93例。随机分为治疗组和对照组。对照组给予β受体阻滞剂、硝酸酯类药物、血管紧张素转换酶抑制剂（ACEI）;治疗组在对照组治疗基础上加用辛伐他汀同时给予低分子肝素。结果治疗组总有效率为93.75%,对照组总有效率为66.67%,治疗组总有效率明显高于对照组,差异有统计学意义（P〈0.05）。结论辛伐他汀和低分子肝素联合治疗不稳定型心绞痛疗效显著。     

Statins Decrease the Occurrence of Venous Thromboembolism in Patients with Cancer

Background

Recent data suggest a reduction in the occurrence of venous thromboembolism in select groups of patients who use statins. The objective of this study is to evaluate the impact of statin use on the occurrence of venous thromboembolism in patients with solid organ tumor.

Methods

We conducted a retrospective, case-control study reviewing 740 consecutive patients with a diagnosis of solid organ tumor who were admitted to the Albert Einstein Medical Center, Philadelphia, Penn, between October 2004 and September 2007. Patients treated with anticoagulation therapy before their first admission were excluded. The occurrence of venous thromboembolism, risk factors for venous thromboembolism, and statin use were recorded. Patients who never used statins or had used them for less than 2 months were relegated to the control group.

Results

The mean age of the study population was 65 years, and 52% of the patients were women and 76% were African American. The occurrence of venous thromboembolism was 18% (N = 132), and 26% (N = 194) were receiving statins. Among patients receiving statins, 8% (N = 16) developed a venous thromboembolism compared with 21% (N = 116) in the control group (odds ratio 0.33; 95% confidence interval, 0.19-0.57). A logistic regression analysis including risk factors for venous thromboembolism (metastatic disease, use of chemotherapy, immobilization, smoking, and aspirin use) along with statin use yielded the same results.

Conclusion

This study suggests that the use of statins is associated with a significant reduction in the occurrence of venous thromboembolism. This pleiotropic effect warrants further investigation.     

Association of Anemia with Venous Thromboembolism in Acutely Ill Hospitalized Patients: An APEX Trial Substudy

Background

Anemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism and whether the presence of anemia can refine risk assessment for prediction of venous thromboembolism, thereby adding incremental utility to a validated model.

Venous Thromboembolism Occurs Frequently in Patients Undergoing Brain Tumor Surgery Despite Prophylaxis

Most Neurosurgical Service patients at our hospital receive venous thromboembolism prophylaxis. In 1995–96, the rate of clinically overt venous thromboembolism was 3.7% among patients undergoing neurosurgery. However, rates were much higher when craniotomy was undertaken for brain tumor. Of 497 who underwent craniotomy for primary (429) or metastatic (68) brain tumor, 47 (9.5%) developed clinically overt venous thromboembolism: 7.5% after primary brain tumor resection and 19% after craniotomy for metastatic cancer. The high rate of venous thromboembolism in craniotomy patients with brain tumor warrants study of alternative measures for preventing thrombus, such as prophylaxis with low molecular weight heparin.