Long-Term Use of Low-Molecular-Weight Heparin (LMWH) for Cancer-Associated Venous Thromboembolism (VTE): Adherence to Recommendations in Clinical Practice Based on Tropique, a Prospective Non-Interventional Observational Study
Authors: Farge Dominique , Gorin Norbert Claude , Debourdeau Philippe , Lamblin Anne , Cajfinger Francis 
Published: October 2019

Abstract
Introduction
Few data are available on the long-term LMWH prescription and treatment follow-up in clinical practice in patients with cancer-associated VTE.
Study objectives were to document the prescription and use of treatment doses of LMWH in cancer patients and to assess adherence to established recommendations.
Methods
Adult cancer patients receiving antineoplastic treatment or palliative care, age ≥18 years, with recent symptomatic VTE in whom treatment with LMWH had been initiated within 7 days prior to inclusion, were eligible to participate in this prospective observational French multicenter study. Patients with a contra-indication to LMWH were not eligible for participation. Main study outcome was the description of LMWH use and prescription in usual medical care. Adherence to recommendations was measured as the proportion of patients receiving a prescription of a LMWH at treatment doses according to the approved dosing schedule and treated for at least 3 months in the absence of severe renal insufficiency (CrCl<30 mL/min) [1, 2]. Assuming a normal patient distribution and the unfavorable hypothesis that only 50% of patients were treated according to the national recommendations, 384 patients were needed to obtain conclusive results with a precision of 5% and a risk error of 5%.
Results
A total of 409 patients aged 65±12.1 years of whom 49.9% female were consecutively included from November 2012 to August 2013. A history of previous VTE was found in 54 (13.2%), surgery or trauma in 100 (24.4%), central venous catheter (CVC) in 303 (74.1%) and immobilization >1 month in 47 (11.5%) patients, respectively. Four (1.03%) patients had severe renal insufficiency.
VTE diagnosis at inclusion included lower-limb deep-vein thrombosis (DVT) in 193 (47.2%), pulmonary embolism in 145 (35.5%), CVC-associated thrombosis in 66 (16.1%), upper-limb DVT in 45 (11.0%) and visceral thrombosis in 16 (3.9%) patients, respectively.
Most cancers were solid tumors gastro-intestinal (24.4%), lung (17.4%) or breast (15.9%); 81% of patients received chemotherapy and 61.4% were metastatic cancers. LMWH prescriptions included dalteparin in 42 (10.3%), enoxaparin in 61 (14.9%), nadroparin in 5 (1.2%) and tinzaparin in 301 (73.6%) patients. Only 4 (1%) patients received LMWH despite severe renal insufficiency. Table 1 –Prescription adherence to recommendations at inclusion [n (%)]Adherence criteriaTinzaparin (N=301)Other LMWH (N=108)All (N=409)Treatment duration > 3 months293 (97.3)108 (100)401 (98.0)Adequate dosing regimen*231 (76.7)14 (13.0)245 (59.9)Adequate dosing schedule296 (98.3)45 (41.7)341 (83.4)Overall adherence219 (72.8)7 (6.5)226 (55.3)
*includes adequate treatment dose and dose adjustment according to recommendations
A total of 274 (67.0%) patients received the recommended treatment dose, while 87 (21.3%) patients received doses exceeding this by more than 10% and 39 (9.5%) patients received doses more than 10% below the recommended doses.
Based on the pre-defined adherence criteria, 226 (55.3%) [95% CI 50.4-60.1] patients had a LMWH prescription consistent with recommendations. Tinzaparin prescriptions were associated with higher adherence scores compared to other LMWH.
During follow-up, actual mean treatment duration was 5.28 ± 2.07 months and 85.7% of patients were treated for 3 months or more
Table 2 - Adherence to recommendations at inclusion according to cancer characteristics (N=409) [n (%)] Cancer characteristics Proportion of study population Proportion of adherence to recommendations Gastro-intestinal Lung Breast Hemato lymphopoietic Other Metastatic Chemotherapy (n=405)* 100 (24.4) 71 (17.4) 65 (15.9) 54 (13.2) 119 (29.1) 251 (61.4) 328 (81.0) 53 (53.0) 37 (52.1) 46 (70.8) 28 (51.9) 62 (52.1) 133 (53.0) 186 (56.7)
*405 patients documented with chemotherapy
At inclusion, the rate of prescriptions consistent with recommendations was low (55.3%) while the highest rate of adherence (70.8%) was observed in patients with breast cancer known to be at rather lower risk of VTE recurrence.
Conclusion
Adherence to treatment duration was adequate whereas dosing regimen was insufficiently compliant with recommendations. Overall adherence with tinzaparin seemed higher compared to other LMWH Management of patients with cancer-associated VTE requires further education and information of health care professionals. Farge D, J Thromb Haemost. 2013 Jan; 11(1):56-70.

Disclosures
Farge: Pfizer: Research Funding; LEO Pharma: Research Funding. Debourdeau:Pfizer: Research Funding; LEO Pharma: Research Funding. Cajfinger:Pfizer: Research Funding; LEO Pharma: Research Funding.