Factor XIa inhibitors reduced recurrent stroke after noncardioembolic stroke or TIA in pooled trials

Design

Systematic review and meta-analysis of three randomised placebo-controlled trials

Population

14,239 participants with acute noncardioembolic ischaemic stroke or TIA on standard antiplatelet therapy

Primary outcome

First stroke (efficacy) and first major bleeding event (safety)

Effect

Any stroke RR 0.75 (95% CI 0.66 to 0.84); major bleeding RR 1.12 (0.87 to 1.44)

This Neurology meta-analysis pooled three randomised, placebo-controlled trials of factor XIa inhibitors in people with acute noncardioembolic ischaemic stroke or TIA, a total of 14,239 participants (6,927 on a factor XIa inhibitor, 7,312 on placebo). The inhibitor was added to standard antiplatelet therapy.

Compared with placebo, the inhibitors reduced any stroke (risk ratio 0.75, 95% CI 0.66 to 0.84), ischaemic stroke (0.74, 0.66 to 0.84) and composite cardiovascular events (0.83, 0.75 to 0.92). Major bleeding was not clearly increased (1.12, 0.87 to 1.44), nor were haemorrhagic stroke, intracranial haemorrhage, any bleeding or all-cause death.

The pooled estimates were largely driven by a single phase 3 trial of 12,327 participants, so this is closer to one large trial than three consistent ones. The bleeding interval is compatible with an increase of up to about 44%, so safety is not settled. The paper pools different agents, which may not behave the same way. This does not change current antithrombotic guidelines.

• Current secondary prevention after noncardioembolic stroke or TIA is unchanged by this meta-analysis.
• Any stroke risk ratio was 0.75; ischaemic stroke 0.74; major bleeding 1.12 (0.87 to 1.44).
• One 12,327-person trial dominates the pooled result.
• Watch for licensing decisions and for CDSCO position before considering use in India.

Why it matters

It raises the possibility of reducing recurrent stroke on top of antiplatelet therapy without a clear rise in major bleeding.

Don't overread it

The pooled estimate is dominated by one trial and combines different drugs, so it cannot show that every factor XIa inhibitor performs alike.

The statistics, in plain English

A risk ratio of 0.75 means a 25% lower relative risk of stroke. The bleeding interval of 0.87 to 1.44 includes 1, so no increase was shown, but it also does not rule out a meaningful increase.

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