Long-Term Efficacy and Safety of Low-Molecular-Weight Heparins (LMWH) for Cancer-Associated Venous Thromboembolism (VTE) in Tropique, a Prospective Non-Interventional Observational Study

Introduction

Long-term treatment with LMWH is the standard therapy for patients with cancer-associated VTE. Recommended treatment regimen include the prescription of LMWH at treatment doses according to approved administration schedule for at least 3 months in the absence of severe renal insufficiency (CrCl<30 mL/min) [1, 2]. The TROPIQUE study documented the prescription and use of long-term treatment with LMWH in cancer patients. Here we report the findings on the secondary outcomes, clinical efficacy and safety.

Methods

Adult patients with cancer-associated VTE receiving antineoplastic treatment or palliative care were eligible to participate. Efficacy outcomes measures were VTE recurrence including deep-vein thrombosis (DVT) and pulmonary embolism (PE), visceral thrombosis and central venous catheter (CVC)-associated thrombosis. Safety outcomes included all and major bleeding according to ISTH definition [3], thrombocytopenia and deaths. Incidences of 7% of VTE recurrence and 6% of major bleeding were expected. With a sample of 384 patients, the rate of VTE recurrence and major bleeding would be detected with a precision of ±2.6% and ±2.4%, respectively, with a 95% confidence interval. A total of 400 patients were therefore planned to be included in the study.

Results

A total of 409 patients with symptomatic cancer-associated VTE (Table 1) 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%), CVC in 303 (74.1%) and an immobilization over 1 month in 47 (11.5%) patients, respectively. At study inclusion, 30 (7.3%) patients had platelet count ≤ 100 x10⁹/L, and 129 (31.5%) had reported anemia while 16 (3.9%) patients had a history of bleeding in the last month. At baseline, more than 80% of patients presented with at least a PE or a lower-limb DVT of s.

Mean treatment duration was 5.28 ± 2.07 months. As the majority of patients were treated with tinzaparin (73.6%), clinical outcomes are therefore presented for tinzaparin, other LMWH and all LMWH (Table 2).

A total of 21 events of VTE recurrence occurred in 19 patients during the overall study period, with a Kaplan-Meir estimate of the probability of VTE recurrence at 6 months of 6.1%.

*Multiple causes of death may have been reported in the same patient; **fatal bleeding reported as LMWH-related; ^#n=99;

^##n=143

Kaplan-Meier estimate of the probability of bleeding at 6 months was 15.9% while corresponding estimates were 18.1% for thrombocytopenia and 34.5% for deaths. Of the five (3.5%) patients who reported fatal bleedings one was reported as related to the LMWH treatment. No heparin-induced thrombocytopenia was reported in the study.

Conclusion

Clinical outcomes were consistent with previous observations in this patient population except a lower incidence of VTE recurrence compared with previous studies. Study results tend to confirm the favorable efficacy and safety profile of LMWH for the long-term treatment of patients with cancer-associated VTE, when used according to recommended treatment duration and respecting contra-indications.

1. Schulman. J Throm Haemost. 2005 Apr;3(4):692-4.

2. Farge J Thromb Haemost. 2013 Jan;11(1):56-70.

3. Debourdeau P, J Thromb Haemost. 2013 Jan;11(1):71-80