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Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials
- et al.
Background
The
safety and efficacy of oral anticoagulation for prevention of major
adverse cardiovascular events in people with atrial fibrillation and
spontaneous intracranial haemorrhage are uncertain. We planned to
estimate the effects of starting versus avoiding oral anticoagulation in
people with spontaneous intracranial haemorrhage and atrial
fibrillation.
Methods
In
this prospective meta-analysis, we searched bibliographic databases and
trial registries using the strategies of a Cochrane systematic review
(CD012144) on June 23, 2023. We included clinical trials if they were
registered, randomised, and included participants with spontaneous
intracranial haemorrhage and atrial fibrillation who were assigned to
either start long-term use of any oral anticoagulant agent or avoid oral
anticoagulation (ie, placebo, open control, another antithrombotic
agent, or another intervention for the prevention of major adverse
cardiovascular events). We assessed eligible trials using the Cochrane
Risk of Bias tool. We sought data for individual participants who had
not opted out of data sharing from chief investigators of completed
trials, pending completion of ongoing trials in 2028. The primary
outcome was any stroke or cardiovascular death. We used individual
participant data to construct a Cox regression model of the time to the
first occurrence of outcome events during follow-up in the
intention-to-treat dataset supplied by each trial, followed by
meta-analysis using a fixed-effect inverse-variance model to generate a
pooled estimate of the hazard ratio (HR) with 95% CI. This study is
registered with PROSPERO, CRD42021246133.
Findings
We
identified four eligible trials; three were restricted to participants
with atrial fibrillation and intracranial haemorrhage (SoSTART
[NCT03153150], with 203 participants) or intracerebral haemorrhage
(APACHE-AF [NCT02565693], with 101 participants, and NASPAF-ICH
[NCT02998905], with 30 participants), and one included a subgroup of
participants with previous intracranial haemorrhage (ELDERCARE-AF
[NCT02801669], with 80 participants). After excluding two participants
who opted out of data sharing, we included 412 participants (310 [75%]
aged 75 years or older, 249 [60%] with CHA2DS2-VASc score ≤4, and 163 [40%] with CHA2DS2-VASc
score >4). The intervention was a direct oral anticoagulant in 209
(99%) of 212 participants who were assigned to start oral
anticoagulation, and the comparator was antiplatelet monotherapy in 67
(33%) of 200 participants assigned to avoid oral anticoagulation. The
primary outcome of any stroke or cardiovascular death occurred in 29
(14%) of 212 participants who started oral anticoagulation versus 43
(22%) of 200 who avoided oral anticoagulation (pooled HR 0·68 [95% CI
0·42–1·10]; I2=0%). Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events (nine [4%] of 212 vs 38 [19%] of 200; pooled HR 0·27 [95% CI 0·13–0·56]; I2=0%). There was no significant increase in haemorrhagic major adverse cardiovascular events (15 [7%] of 212 vs nine [5%] of 200; pooled HR 1·80 [95% CI 0·77–4·21]; I2=0%), death from any cause (38 [18%] of 212 vs 29 [15%] of 200; 1·29 [0·78–2·11]; I2=50%), or death or dependence after 1 year (78 [53%] of 147 vs 74 [51%] of 145; pooled odds ratio 1·12 [95% CI 0·70–1·79]; I2=0%).
Interpretation
For
people with atrial fibrillation and intracranial haemorrhage, oral
anticoagulation had uncertain effects on the risk of any stroke or
cardiovascular death (both overall and in subgroups), haemorrhagic major
adverse cardiovascular events, and functional outcome. Oral
anticoagulation reduced the risk of ischaemic major adverse
cardiovascular events, which can inform clinical practice. These
findings should encourage recruitment to, and completion of, ongoing
trials.
Funding
British Heart Foundation.
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