Anticoagulant Treatment Patterns and Outcomes in Patients with Venous Thromboembolism and Active Cancer - a Nationwide Cohort Study in France

BACKGROUND: Cancer is a major risk factor for venous thromboembolism (VTE) and for all-cause mortality following a VTE event. Higher risk can be attributed to certain cancer types and to metastatic disease. Until recently the gold standard for VTE and active cancer was low molecular weight heparin (LMWH), shown to be superior to warfarin in preventing thrombosis (Lee et al. 2003). Previously only minimal data from the direct oral anticoagulant (DOAC) pivotal RCTs were available in this population. However recent RCTs have been conducted that provide rationale for the use of DOACs as an alternative to LMWH in this patient group (Agnelli et al. 2020; Raskob et al. 2018; Young et al. 2018). This evidence is reflected in international guidelines (ASH 2021; ESC 2019; ITAC 2019, NCCN 2021) where DOACs are now proposed in VTE and active cancer patients without gastrointestinal cancer.

PURPOSE: To describe patient characteristics, anticoagulant (AC) treatment patterns and outcomes among patients with VTE and active cancer in France. The analysis included all relevant ACs that were available for the treatment of VTE to understand how treatment recommendations were being reflected in clinical practice.

METHODS: A nationwide retrospective cohort study of all adult patients (identified via the French national health data system: SNDS) with VTE and active cancer prescribed LMWH, a vitamin K antagonist (VKA), or a DOAC (apixaban or rivaroxaban) from 2013 to 2018. AC treatment-naïve (defined as patients without an AC prescription 24 months prior to index VTE) and AC treatment-experienced patients were included. Active cancer was defined by the presence of medical claims for cancer diagnosis or cancer-specific treatment in the 6 months prior or 30 days after index VTE event. A modified Khorana VTE risk scale (based on ICD codes and not blood tests) was used to evaluate the distribution of baseline VTE risk associated with different cancers. Rates of bleeding (defined as principal diagnoses of hospital stays), recurrent VTE, and all-cause mortality were assessed at 6 months for the standard of care (LMWH) cohort.

RESULTS: 39,023 patients with VTE and active cancer were included. Most patients were prescribed LMWH 31,771 (81.42%), followed by rivaroxaban 2,259 (5.79%), VKAs 1,591 (4.08%), and apixaban 678 (1.74%). 2,724 (6.98%) were prescribed other parenteral anticoagulants (PAC) or PAC combinations. A slightly lower proportion of patients prescribed LMWH or VKAs were AC treatment naïve (44.4% and 45% respectively) compared to those prescribed rivaroxaban (51.2%) or apixaban (51.6%). Median duration of treatment (months; IQR) was shortest for LMWH patients (3.84; 1.35-8.48) and similar amongst the other ACs: VKAs (5.26; 1.05-14.16), rivaroxaban (5.85; 1.91-10.74), and apixaban (5.73; 1.74-9.07).

Patients initiating VKAs and apixaban were older than those initiating rivaroxaban or LMWH (mean age in years: VKAs, 74; apixaban, 73; rivaroxaban, 67; LMWH, 66) however, LMWH patients had a higher comorbidity burden (mean CCI score: LMWH 6.4, VKAs, 4.95; rivaroxaban, 4.20; apixaban, 4.31). The proportion of patients with pulmonary embolism (PE), with or without DVT, was lower for LMWH and VKA cohorts (58.74% and 61.85% respectively) compared to rivaroxaban (71.76%) and apixaban (69.32%).

Amongst patients with a medical claim for cancer diagnosis, the majority receiving LMWH (19,300 (61.8%)) had cancers with very high risk (brain, pancreatic, stomach) or high risk (gynaecological, lung, lymphoma, testicular, renal cell) for VTE. This proportion was lower in patients receiving VKAs, 484 (40.27%); rivaroxaban, 719 (43.52%); or apixaban, 194 (40%). Metastatic disease was present in most LMWH patients 21,994 (72.14%) but only in about a third of those receiving other ACs: VKAs, 406 (34.18%); rivaroxaban, 591 (36.37%); and apixaban, 152 (31.73%).

Event rates for LMWH are reported in the table.

CONCLUSIONS: AC therapy for a significant majority of patients with VTE and active cancer was LMWH. Most LMWH patients had metastatic disease. Median LMWH treatment was less than 4 months and VTE-related clinical event rates remained high in this population, suggesting a key unmet medical need. Future studies reflecting potential changes in clinical practice, because of guideline updates and the emergence of new RCT evidence, are required to understand clinical outcomes with different AC treatments.

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