Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer.

In 2 double-blind studies, ambulatory patients with objectively proven, disseminated metastatic breast carcinoma (TOPIC-1) or stage III/IV non-small-cell lung carcinoma (TOPIC-2) were randomized to certoparin 3000 IU or placebo subcutaneously once daily, for 6 months. Primary efficacy outcome was objectively confirmed symptomatic or asymptomatic venous thromboembolism (VTE). Safety outcomes included bleeding (major and minor), and thrombocytopenia. TOPIC-1 was halted after an interim analysis. Venous thromboembolism occurrence was not different between treatment groups in TOPIC-1 (4% treated with certoparin, 7 of 174 vs 4% receiving placebo, 7 of 177, odds ratio [OR] 1.02; 95% confidence interval [CI] 0.30-3.48) and in TOPIC-2 (4.5%, 12 of 268) vs 8.3%, 22 of 264, respectively, OR 0.52; CI 0.23-1.12). Mortality was not different between groups. A post hoc analysis showed certoparin significantly reduced VTE in stage IV lung carcinoma (3.5% vs 10.2%; P = .032) without increased bleeding. In conclusion, thrombosis risk and prophylactic benefit was highest in stage IV lung carcinoma patients.

Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients.

BACKGROUND: The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome--2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.).

An evaluation of venous thromboembolic risk in acutely ill medical patients immobilized at home: the AT-HOME Study.

Many risk factors for venous thromboembolism (VTE) in hospitalized medical patients are also present in medical outpatients. VTE prevention represents an important challenge for physicians treating patients at home. The AT-HOME study was a prospective cross-sectional observational study designed to assess awareness of the risk of VTE in immobilized acutely ill medical outpatients among German physicians, many of whom were participating in a national Continuing Medical Education (CME) program designed to raise awareness of VTE. The study involved 1210 medical patients who were acutely confined to bed at home. Physicians performed a subjective assessment of VTE risk, which was rated on a 10-point scale (1 = very low risk; 10 = very high risk). The risk of VTE was also assessed retrospectively by using a scorecard developed for use in hospitalized medical patients. Of the 1210 patients, 198 (16%) had risk scores of 0-4, 319 (26%) had scores of 5 or 6, and 693 (57%) had scores > or =7. Overall, 966 patients (80%) received thromboprophylaxis. The proportion of patients receiving thromboprophylaxis was 0% to 47% in risk score groups 0-4, 76% to 85% in groups 5 and 6, and 90% to 100% in risk score groups 7-10. In the retrospective assessment of VTE risk, 74% of patients were at high risk, 15% were at intermediate risk, and 11% were at low risk. The proportions of patients receiving thromboprophylaxis in these groups were 87%, 61%, and 55%, respectively. The involvement of physicians in educational activities focusing on VTE awareness appeared to create awareness of the risks of VTE in acutely ill medical outpatients.

Venous thromboembolic risk and its prevention in hospitalized medical patients.

In medical patients, the risk of venous thromboembolism (VTE) is substantially underestimated and prophylaxis is used far less than in surgical patients, reflecting the scarcity of evidence supporting antithrombotic therapy in nonsurgical settings. However, current consensus documents recommend assessment of all medical, as well as surgical, patients for thromboembolic risk and provide prophylaxis recommendations according to the risk level, determined by the presence of different clinical and molecular risk factors. Although long-term, underlying clinical and molecular risk factors also have a major impact on overall risk in medical patients; risk clearly varies with the type of medical condition. Myocardial infarction, stroke, and malignant disease are linked to a high rate of VTE; recent evidence highlights patients with cardiopulmonary disease as a distinct risk group. Despite skepticism in some quarters, high-quality evidence confirms the efficacy of unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) in reducing asymptomatic deep vein thrombosis (DVT) in a broad spectrum of medical patients; further studies are required to clarify the effect on fatal pulmonary embolism (PE). Emerging data from the recent PRINCE and MEDENOX studies demonstrate that the LMWH enoxaparin provides effective and well-tolerated VTE prevention in patients with severe cardiopulmonary disease. Emerging evidence has led to a grade 1A recommendation for the use of thromboprophylaxis in these patients in the most recent consensus conference on thromboprophylaxis. Further studies, however, are required to clarify the optimal duration of prophylaxis in medical patients and to evaluate the potential role of outpatient prophylaxis. Accurate risk assessment and prompt implementation of appropriate prophylaxis, selected on the basis of evidence from well-designed controlled clinical trials, may reduce the future morbidity and mortality due to VTE in medical patients.