Tinzaparin sodium 20,000units/2ml solution for injection vials

About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions.To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT.For this individual patient data meta-analysis, we used data from four randomized controlled trials evaluating low-molecular-weight heparin or direct oral anticoagulants (DOACs) for CAT (Hokusai VTE Cancer, SELECT-D, CLOT, and CATCH). The primary outcome was adjudicated on-treatment recurrent CAT during a 6-month follow-up. A clinical prediction model was developed using multivariable logistic regression analysis with backward selection. This model was validated using internal-external cross-validation. Performance was assessed by the c-statistic and a calibration plot.After excluding patients using vitamin K antagonists, the combined dataset comprised 2,245 patients with cancer and acute CAT who were treated with edoxaban (23%), rivaroxaban (9%), dalteparin (47%), or tinzaparin (20%). Recurrent on-treatment CAT during the 6-month follow-up occurred in 150 (6.7%) patients. Predictors included in the final model were age (restricted cubic spline), breast cancer (odds ratio [OR]: 0.42; 95% confidence interval [CI]: 0.20-0.87), metastatic disease (OR: 1.44; 95% CI: 1.01-2.05), treatment with DOAC (OR: 0.66; 95% CI: 0.44-0.98), and deep vein thrombosis only as an index event (OR: 1.72; 95% CI: 1.31-2.27). The c-statistic of the model was 0.63 (95% CI: 0.54-0.72) after internal-external cross-validation. Calibration varied across studies.The prediction model for recurrent CAT included five clinical predictors and has only modest discrimination. Prediction of recurrent CAT at the initiation of anticoagulation remains challenging.

Abstract licence: CC BY

BackgroundRisk of venous thromboembolism (VTE) recurrence remains high in patients with cancer-associated thrombosis (CAT), despite therapeutic anticoagulation. Identifying patients at risk of treatment failure is still a challenge.ObjectivesWe aimed to assess the performance of the Ottawa score in predicting VTE recurrence in a large homogeneous population of patients with CAT treated with the same anticoagulant, tinzaparin, for at least 3 months.MethodsIndividual patient data from 3 prospective cohort studies and 1 randomized controlled trial were pooled (PROSPERO: CRD42019119907). Clinical events of interest were adjudicated by independent central adjudication committees in all 4 studies.ResultsAmong the 1413 patients included, the Ottawa score could be calculated for 1088 of whom 646 (59.4%) were classified at high risk of recurrence (Ottawa score ≥ 1). The 6-month cumulative incidence of recurrent VTE was 5.0% (95% CI, 3.2-7.8) in the Ottawa low-risk group and 8.5% (95% CI, 6.6-10.8) in the high-risk group. The area under the receiver operating characteristic curve was 0.56 (95% CI, 0.51-0.62). The sensitivity of the dichotomized Ottawa score (score ≥ 1) was 72.8% (95% CI, 62.6%-83.0%), the specificity was 41.9% (95% CI, 37.8%-45.9%), the positive predictive value was 8.6% (95% CI, 6.4%-10.8%), and the negative predictive value was 95.3% (95% CI, 93.3%-97.4%). Introducing additional predictive factors failed to significantly improve the score's performance.ConclusionsDespite the large number of patients and anticoagulant treatment standardization, the Ottawa score failed to accurately predict recurrent VTE in patients with CAT treated with tinzaparin.

Abstract licence: CC BY

Abstract Background: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin (Innohep®) is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this study is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE, in pregnant women, cancer patients and individuals suffering from renal impairment. Methods: We identified clinical trials reporting safety outcomes for pregnant women, cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. We extracted predefined, clinically relevant outcomes of patients on tinzaparin.Results: For pregnant women on tinzaparin bleeding rates ranged from 9.7% to 10.3%; reported rates of major bleeding events, allergic reactions and thrombocytopenia were low. No maternal deaths or neonatal hemorrhages were recorded. Prophylactic administration of tinzaparin also showed promising results in pregnant women with recurrent unexpected pregnancy loss. In patients with cancer bleeding rates fluctuated between 0.8% and 27%; there was a trend showing that patients on tinzaparin exhibited fewer bleeding events than those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Therapeutic administration of tinzaparin did not produce significant increase in the rates of clinically relevant or major bleeding events in patients with renal impairment. Periodic administration of tinzaparin did not result in bioaccumulation and tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance < 20 ml/min.Conclusions: Tinzaparin represents a thoroughly studied and safe choice for special populations that are at increased risk for both thrombosis and bleeding. Tinzaparin is safe for pregnant women. Current literature supports the use of tinzaparin without dose adjustment in patients with renal impairment and creatinine clearance < 20ml/min.

Abstract licence: CC BY 4.0

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

Abstract licence: CC BY 4.0