Dabigatran for the Treatment and Secondary Prevention of Venous Thromboembolism; A Cost-Effectiveness Analysis for the Netherlands

Background Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. Methods Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RESONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). Results In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving epsilon 1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of epsilon 20,000/ QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at epsilon 2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at epsilon 33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. Conclusion From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands

Salt-Induced Disintegration of Lysozyme-Containing Polyelectrolyte Complex Micelles

The salt-induced disintegration of lysozyme-filled polyelectrolyte complex micelles, consisting of positively charged homopolymers (PDMAEMA150), negatively charged diblock copolymers (PAA42-PAAm417), and lysozyme, has been studied with dynamic light scattering (DLS) and small-angle neutron scattering (SANS). These measurements show that, from 0 to 0.2 M NaCl, both the hydrodynamic radius (Rh) and the core radius (Rcore) decrease with increasing salt concentration. This suggests that the micellar structures rearrange. Moreover, from 0.2 to 0.4 M NaCl the light-scattering intensity is constant. In this salt interval, the hydrodynamic radius increases, has a maximum at 0.3 M NaCl, and subsequently decreases. This behavior is observed in both a lysozyme-containing system and a system without lysozyme. The SANS measurements on the lysozyme-filled micelles do not show increased intensity or a larger core radius at 0.3 M NaCl. This indicates that from 0.2 to 0.4 M NaCl another structure is formed, consisting of just the diblock copolymer and the homopolymer, because at 0.12 M NaCl the lysozyme-PAA42-PAAm417 complex has disintegrated. One may expect that the driving force for the formation of the complex in this salt range is other than electrostati

A new class of supramolecular thermoplastic elastomers for self-healing coatings

A supramolecular material exhibiting self-healing properties was studied in this work. The material is based on the mixture of two ABA-type oligomeric triblock copolymers, the first consisting of positively charged end blocks and the second one of negatively charged ones. Each oligomeric triblock consists of a soft middle block and soft end blocks. When mixed together the resulting material phase-separates in an electrostatically assembled phase with a high glass transition temperature (Tg) and an uncharged phase with a low Tg. The mechanical and physical properties of the resulting thermoplastic elastomer can be tuned by varying the size of the charged blocks, using different polymer architectures and using different monomers. The building block oligomers are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization using a bifunctional chain transfer agent and purified by precipitation. Characterization was done by Modulated Differential Scanning Calorimetry (MDSC), Dynamic Mechanical Thermal Analysis (DMTA) and Transmission Electron Microscopy (TEM). The self-healing behaviour of the coating was studied under optical microscope proving self-healing abilities after scratching

Cost parameters applied in the model.

<p>VKA, vitamin K antagonists; LMWH, low molecular weight heparins; INR, international normalised ratio; MCRB, major or clinically relevant bleeding; DVT, deep vein thrombosis; PE, pulmonary embolism; CRNMB = clinically relevant non-major bleed event; ICH = intracranial haemorrhage; MB = major bleed; MI = myocardial infarction; UA, unstable angina; CTEPH = chronic thromboembolic pulmonary hypertension; PTS = post thrombotic syndrome GP, general practitioner.</p

Recurrent VTE, bleeding complications and other adverse events and related costs within a hypothetical patient population of 10,000 subjects receiving dabigatran and VKA over a lifetime horizon.

<p>VKA, vitamin K antagonists; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; r, recurrent; LMWH, low molecular weight heparin; CRNMB = clinically relevant non-major bleed event; ICH = intracranial haemorrhage; MB = major bleed; MI = myocardial infarction; CTEPH = chronic thromboembolic pulmonary hypertension; PTS = post thrombotic syndrome; UA, unstable angina; INR, international normalised ratio.</p

Results of the base-case and scenario analyses.

<p>VKA, vitamin K antagonists; ICER, incremental cost-effectiveness ratio; QALY, quality adjusted life year; LY, life year.</p