Benefit of Fondaparinux in Medical Patients: A Subgroup Analysis.

Abstract

Aim In the ARTEMIS study fondaparinux 2.5mg reduced the overall incidence of venous thromboembolism (VTE) by 47% in general medical patients when compared to placebo. Our aim was to identify which medical patient populations with an acute medical illness or risk factor for VTE benefited from fondaparinux prophylaxis. Method A total of 849 patients were enrolled in 35 centres in 8 countries. Patients were randomised to receive placebo or fondaparinux 2.5mg subcutaneously once daily for 6 to 14 days. 644 (76%) patients were available for assessment of the primary outcome, occurrence of documented VTE between day 1 and day 15. We performed a subgroup analysis of the incidence of VTE in the placebo and fondaparinux 2.5mg treatment groups. The medical illness subgroups analysed were those predefined in the original study: acute heart failure only, respiratory disease only, infectious/inflammatory disease only and more than one disease. Results Conclusion Fondaparinux 2.5mg is superior to placebo in preventing VTE in patients with acute medical illness. Similar point estimates and overlapping confidence intervals indicate that the results are consistent within all the predefined medical illness. Population variable Placebo Fondaparinux 2.5mg Relative risk reduction 95% CI * P Value n/N % n/N % *exact CI for RRR based on standardized statistics and inverting a 2-sided test Acute heart failure (NYHA III/IV) 10/82 12.2 7/78 9.0 26.4% [−78.9%;69.7%] 0.61 Acute respiratory disease only 4/73 5.5 1/63 1.6 71.0% [−86.6%;97.7%] 0.37 Acute infectious/inflammatory disease only 10/88 11.4 4/77 5.2 54.3% [−33.1%;85.0%] 0.17 More than one disease 10/80 12.5 6/103 5.8 53.4% [−21.4%;83.4%] 0.12

Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients: A U.S. Perspective

“…[48][49][50] Placebocontrolled trials that included patients over 40 years of age, immobility, and additional VTE risk factors compared placebo groups to the LMWHs enoxaparin 40 mg subcutaneously daily and dalteparin 5000 IU subcutaneously daily, or the pentasaccharide fondaparinux 2.5 mg subcutaneously daily with primary efficacy endpoints that were based mostly on lower extremity venographic or ultrasonographic endpoints. [11][12][13] These trials have shown a 50 to 60% reduction in total VTE with a trend toward a numeric excess in MB events. All of these studies had a 6-to 14-day treatment duration.…”

“…10 The results of older inpatient-based randomized placebo-controlled trials with unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or pentasaccharide fondaparinux have shown a 50 to 60% reduction of total VTE that included both symptomatic VTE and asymptomatic lower extremity DVT (established by screening venography or ultrasonography) that firmly established the effectiveness and net clinical benefit of short term use of thromboprophylaxis given for a duration of 6 to 14 days. [11][12][13] This recommendation has been supported by antithrombotic guidelines. 14 However, the shortened hospital length-of-stay in the U.S., which now averages 4.5 days, coupled with fewer than 4% of hospitalized medically ill patients in the U.S. receiving postdischarge thromboprophylaxis, has dampened the treatment effects of in-hospital thromboprophylaxs.…”

Cancer-Associated Thrombosis: Beyond Clinical Practice Guidelines—A Multidisciplinary (SEMI–SEOM–SETH) Expert Consensus

“…In fact, recommendations are based on the results of trials whose cohorts consisted of heterogeneous groups of medical patients, among which cancer patients were underrepresented (5-15%). [19][20][21][22][23] A recent meta-analysis restricted to the cancer subgroup of the aforementioned studies did not confirm a positive effect of thromboprophylaxis. 24 On the other hand, cancer patients also exhibit an increased bleeding tendency and are considered as a highrisk population for hemorrhages.…”

Derivation and Validation of a Prediction Model for Venous Thromboembolism in Primary Care

“…27 In other words, the action threshold was not limited to a unique cutoff but ranged between the likelihood to prevent VTE or cause bleeding (i.e., gastrointestinal bleeding and/or hemorrhagic stroke). 2,3,28,29 In the present study, NB of our prediction model was compared with default policies of "treat all," which was calculated by assuming that all patients were treated with thromboprophylaxis using LMWH or fondaparinux, and "treat none" which means that NB was zero. Finally, with the aim of supporting GPs in clinical decision-making, we complemented the DCA by proposing a score categorization into four different risk subgroups, using cut-points on the prognostic index determined by Cox's methods.…”