‘Patients treated with DES do not live longer’
A study presented in a Hot Line session yesterday suggested that a decoy protein can rapidly reverse potentially life-threatening bleeding effects associated with anticoagulants.
Interim results from the ongoing ANdexanet alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors (ANNEXA-4) study, published simultaneously in the New England Journal of Medicine, show the antidote andexanet alfa reduces anticoagulant activity within half an hour in nearly 90% of patients.
NOACs are considered safe but are associated with increased risk of major gastrointestinal bleeding. Andexanet alfa is the first agent designed to reverse effects of these newer oral anticoagulants which inhibit factor Xa enzyme. A modified recombinant derivative of factor Xa, andexanet alfa acts as a decoy receptor.
It has been shown to reduce anti-fXa activity in volunteers but, until now, there was no data for acutely bleeding patients. The interim results from the ANNEXA-4 study are based on 67 patients with a mean age of 77 years requiring urgent reversal of acute major bleeding. This was within 18 hours of receiving either a direct fXa inhibitor (such as apixaban, rivaroxaban or edoxaban) or an indirect one (enoxaparin).
The main site of bleeding was either gastrointestinal (49%) or intracranial (42%). The study was not randomised (for ethical reasons) and all patients received andexanet, first in an immediate IV bolus over 15 to 30 minutes and then followed by a two hour IV infusion. Dosing was based on exposure to fXa inhibitor.
Patients were assessed at baseline, at end-of-bolus, and at end of the two-hour infusion. Assessment also took place at four, eight and 12 hours, and safety follow-up visits occurred at three and 30 days post-infusion.
The primary outcomes were based on primary efficacy measurements and on safety measurements. The former included change in anti-fXa activity and clinical hemostatic efficacy through 12 hours using independent adjudication committee with pre-specified precise evaluation criteria. The latter covered overall safety; thrombotic events; antibodies to FX, FXa, andexanet; and 30-day all-cause mortality.
The interim results reported an 89% decrease in anti-fXa activity from baseline to end-of-bolus for those patients exposed to rivaroxaban, and a 93% reduction for those exposed to apixaban. Clinical haemostatic efficacy was rated as ‘excellent or good’ in 79% of patients at 12 hours.
Thrombotic events occurred in 18% of patients during 30 day follow-up. Study presenter Stuart Connolly from McMaster University in Canada.said this was not unexpected given the ‘highly compromised’ profile of patients and that anticoagulation was discontinued at the time of bleeding and not restarted.
‘The preliminary report of the ongoing ANNEXA-4 study shows us that andexanet rapidly reverses anti-factor Xa activity in acutely bleeding patients and this is associated with excellent or good haemostatis in most,’ Connolly.added.
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