Antithrombotic Treatment With Factor XIa Inhibition to Optimize Management of Acute Thromboembolic Events for Secondary Stroke Prevention - AXIOMATIC-SSP

Sep 07, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bristol-Myers Squibb–Janssen Alliance
Date Presented:
08/28/2022
Original Posted Date:
09/07/2022
References

Contribution To Literature:

In the AXIOMATIC-SSP trial, milvexian did not reduce the composite of covert brain infarction or ischemic stroke at 90 days compared with placebo in patients with ischemic stroke or TIA on a background of antiplatelet therapy.

Description:

The goal of the trial was to assess the safety and efficacy of 5 doses of milvexian compared with placebo in patients with ischemic stroke or transient ischemic attack (TIA).

Study Design

This was a phase II trial. Patients were randomized in a double-blind 1:1:1:1:1:2 fashion to either milvexian 25 mg daily (n = 325), milvexian 25 mg BID (n = 313), milvexian 50 mg BID (n = 325), milvexian 100 mg BID (n = 306), milvexian 200 mg BID (n = 344) or matching placebo (n = 682). All participants were also on 75 mg clopidogrel + 100 mg aspirin; dual antiplatelet therapy was continued for 21 days and then switched to aspirin 100 mg daily thereafter.

  • Total number of enrollees: 2,295
  • Duration of follow-up: 90 days

Inclusion criteria:

  • Nonlacunar stroke
  • Visible atherosclerosis
  • NIHSS (National Institutes of Health Stroke Scale) score ≤7
  • ABCD2 (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) score ≥6
  • ≤48 hours after symptom onset

Exclusion criteria:

  • Predicted inability to swallow study medication
  • Any condition that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk of bleeding
  • Use of thrombolytic therapy or mechanical thrombectomy for treatment of index stroke

Principal Findings:

The primary efficacy outcome, symptomatic ischemic stroke and covert brain infarction at 90 days, was not different between milvexian and placebo.

All Bleeding Academic Research Consortium (BARC) bleeding, for milvexian 25 mg daily vs. 25 mg BID vs. 50 mg BID vs. 100 mg BID vs. 200 mg BID vs. placebo, was: 10.8% vs. 8.6% vs. 12.3% vs. 13.1% vs. 10.2% vs. 7.9% (p > 0.05).

  • Secondary outcomes for milvexian 25 mg daily vs. 25 mg BID vs. 50 mg BID vs. 100 mg BID vs. 200 mg BID vs. placebo:
  • Symptomatic ischemic stroke or TIA: 4.6% vs. 3.8% vs. 4.0% vs. 3.5% vs. 7.7% vs. 5.5% (p > 0.05)
  • Symptomatic intracranial hemorrhage: 0% vs. 0% vs. 0.9% vs. 0% vs. 0.3% vs. 0.3% (p > 0.05)
  • Fatal bleeding: 0

Interpretation:

The results of this phase II trial indicate that milvexian did not reduce the composite of covert brain infarction or ischemic stroke at 90 days compared with placebo in patients with ischemic stroke or TIA on a background of antiplatelet therapy. No increase in bleeding was noted. Milvexian will be tested in a phase III trial among patients with ischemic stroke.

Milvexian is a novel oral factor XIa inhibitor that is being evaluated across a variety of indications.

References:

Presented by Dr. Mukul Sharma at the European Society of Cardiology Congress (ESC 2022), Barcelona, Spain, August 28, 2022.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Novel Agents

Keywords: Aspirin, Atherosclerosis, Blood Pressure, Brain Infarction, Clopidogrel, Diabetes Mellitus, ESC22, ESC Congress, Factor XIa, Intracranial Hemorrhages, Ischemic Attack, Transient, Ischemic Stroke, Platelet Aggregation Inhibitors, Secondary Prevention, Thromboembolism, Vascular Diseases


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