Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has published a final guidance recommending the anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) as an option for treating and preventing recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults.
The guidance says dabigatran can provide a benefit for these patients, with cost- and clinical-effectiveness similar to rivaroxaban and added convenience compared to warfarin.
“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly, and having to adjust the dose of the
drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”
NICE expects dabigatran to be available on the National Health Service within 3 months.
Cost considerations
Dabigatran costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding tax) and £2.20 per day of treatment, although costs may vary in different settings.
The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment was uncertain.
However, both Boehringer Ingelheim’s and the evidence review group’s exploratory ICER remained in the range that could be considered a cost-effective use of National Health Service resources. That is, both were under £20,000 per quality-adjusted life-year gained (QALY).
Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of venous thromboembolism (VTE) in their indirect comparisons, and the costs were also very similar between these two treatments.
For combined treatment and secondary prevention of VTE, the appraisal committee said the company’s base case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).
But the evidence review group’s exploratory base case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the ICER probably lies somewhere between these estimates.
Clinical evidence
To assess the clinical effectiveness of dabigatran, the appraisal committee evaluated data from the RECOVER, RE-MEDY, and RESONATE trials.
In the first RE-COVER trial, dabigatran proved noninferior to warfarin for preventing VTE recurrence, and rates of major bleeding were similar between the treatment arms.
However, patients were more likely to discontinue dabigatran due to adverse events. Results from this trial were presented at ASH 2009 and published in NEJM.
The RE-COVER II trial also suggested that dabigatran was noninferior to warfarin for preventing VTE recurrence and related deaths, and dabigatran was associated with a lower rate of major bleeding.
Rates of death, adverse events, and acute coronary syndromes were similar between the treatment arms. Results from this trial were published in Circulation in 2013.
The RE-MEDY and RE-SONATE trials were designed to evaluate dabigatran as extended VTE prophylaxis. Results of both trials were reported in a single NEJM article published in 2013.
The RE-MEDY trial suggested that dabigatran was noninferior to warfarin as extended prophylaxis for recurrent VTE, and warfarin presented a significantly higher risk of bleeding.
Results of the RE-SONATE trial indicated that dabigatran was superior to placebo for preventing recurrent VTE, although the drug significantly increased the risk of major or clinically relevant bleeding.
