Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a single technology appraisal

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission’s evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1–4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70–79% in THR and 31–49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturer’s economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below £200 and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of £5000 and £8000 respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban comparing RECORD 4 with RE-MODEL and RE-MOBILIZE, and was more cost-effective than rivaroxaban comparing RECORD 3 (incremental cost per QALY gained of rivaroxaban compared with dabigatran of £123,000) or RECORD 3 and RECORD 4 pooled (incremental cost per QALY gained of dabigatran compared with rivaroxaban of £400) with RE-MODEL and RE-MOBILIZE. In conclusion, the evidence indicates that rivaroxaban is not inferior to enoxaparin in terms of the primary and secondary outcomes. The submission presents a reasonable estimation of the cost-effectiveness of rivaroxaban compared with enoxaparin and dabigatran, although the uncertainty in the decision has been underestimated. The results are particularly sensitive to any assumed difference in the number of fatal PEs, but the ERG does not believe there is sufficient evidence to support a difference between interventions. The NICE guidance issued as a result of the STA states that: riveroxaban, within its marketing authorisation, is recommended as an option for the prevention of venous thromboembolism in adults having elective THR or elective TKB.

Download Full-text

Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal

Health Technology Assessment ◽

10.3310/hta13suppl3/07 ◽

2009 ◽

Vol 13 (Suppl 3) ◽

Cited By ~ 5

Author(s):

M Stevenson ◽

A Scope ◽

M Holmes ◽

A Rees ◽

E Kaltenthaler

Keyword(s):

Venous Thromboembolism ◽

Technology Appraisal ◽

Single Technology Appraisal

Download Full-text

Identifying positive deviants in healthcare quality and safety: a mixed methods study

Journal of the Royal Society of Medicine ◽

10.1177/0141076818772230 ◽

2018 ◽

Vol 111 (8) ◽

pp. 276-291 ◽

Cited By ~ 8

Author(s):

Jane K O’Hara ◽

Katja Grasic ◽

Nils Gutacker ◽

Andrew Street ◽

Robbie Foy ◽

...

Keyword(s):

Mixed Methods ◽

Statistical Modelling ◽

Service Level ◽

Knee Surgery ◽

Mixed Methods Study ◽

Quality And Safety ◽

Hospital Data ◽

Local Improvement ◽

Patient Reported ◽

Hip And Knee Surgery

Objective Solutions to quality and safety problems exist within healthcare organisations, but to maximise the learning from these positive deviants, we first need to identify them. This study explores using routinely collected, publicly available data in England to identify positively deviant services in one region of the country. Design A mixed methods study undertaken July 2014 to February 2015, employing expert discussion, consensus and statistical modelling to identify indicators of quality and safety, establish a set of criteria to inform decisions about which indicators were robust and useful measures, and whether these could be used to identify positive deviants. Setting Yorkshire and Humber, England. Participants None - analysis based on routinely collected, administrative English hospital data. Main outcome measures We identified 49 indicators of quality and safety from acute care settings across eight data sources. Twenty-six indicators did not allow comparison of quality at the sub-hospital level. Of the 23 remaining indicators, 12 met all criteria and were possible candidates for identifying positive deviants. Results Four indicators (readmission and patient reported outcomes for hip and knee surgery) offered indicators of the same service. These were selected by an expert group as the basis for statistical modelling, which supported identification of one service in Yorkshire and Humber showing a 50% positive deviation from the national average. Conclusion Relatively few indicators of quality and safety relate to a service level, making meaningful comparisons and local improvement based on the measures difficult. It was possible, however, to identify a set of indicators that provided robust measurement of the quality and safety of services providing hip and knee surgery.

Download Full-text

Anticoagulant dosing in renal impairment

Phlebologie ◽

10.12687/phleb2290-6-2015 ◽

2015 ◽

Vol 44 (06) ◽

pp. 316-319 ◽

Cited By ~ 2

Author(s):

S. Harder

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Renal Impairment ◽

Anticoagulant Therapy ◽

Severe Renal Impairment ◽

Dabigatran Etexilate ◽

The Elderly ◽

Thrombin Inhibitor ◽

Safety And Efficacy ◽

Direct Acting

SummaryAnticoagulants are widely used for prophylaxis and treatment of venous thromboembolism in the elderly, who commonly have renal impairment and other comorbidities. Renal impairment is a risk factor for bleeding and thrombosis during anticoagulant therapy and can influence the balance between the safety and efficacy of such agents. Some anticoagulants, such as fondaparinux and the direct acting oral thrombin inhibitor dabigatran etexilate are contraindicated for use in patients with severe renal impairment (eGFR <30 ml/min). However, also the direct acting oral FXa-inhibitors rivaroxaban, edoxaban and apixaban need caution regarding dosing advice or contraindications when used in patients with renal impairment.

Download Full-text