Journal Club Summary
Connolly SJ, et al. N Engl J Med. 2019 Feb 7.
Question and Methods: This was the first trial looking at clinical outcomes for reversal of factor Xa inhibitor anticoagulation in major bleeding episodes using the specific reversal agent, Andexanet alfa. It was a multi-centre, open label trial without a comparison group.
Findings: They found large reductions (~92%) in anti-Xa activity levels at treatment nadir, judged 82% of patients to have excellent or good hemostasis, 14% mortality rate, 10% thrombotic complication rate but most importantly they found no correlation between hemostatic outcome and anti-factor Xa reduction.
Limitations: Industry sponsored and designed, no randomization and lack of placebo/comparison group, surrogate outcomes, clinical outcomes were not patient oriented, excluded patients with expected survival of less than 1 month.
Interpretation: Unfortunately, based on the methodology and lack of comparison group, this study alone cannot tell us whether this medication will have a positive clinical impact when used and with a price tag of $30 000 – $60 000 per treatment cannot be recommended over PCC at this point and I would wait for more robust, placebo-controlled RCT data with patient-centred outcomes.
By: Dr. Rob Suttie
Without a comparator group, it is impossible to determine how effective a treatment option is. In this study, while mortality is high, this may be much lower than treating with PCC or with plasma. While outcomes can be assessed, in the absence of a comparator group neither associations nor causality relationships can be determined, only hypotheses may be generated.
By: Dr. Jeff Perry