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4/The impact of atrial fibrillation type on risks of stroke and systemic embolism major haemorrhage and mortality in patients with previous stroke – a systematic review and meta-analysis

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Aims: Atrial fibrillation (AF) is an independent risk factor for stroke recurrence in patients with prior stroke. However, there is conflicting evidence on the impact of AF type, either non-paroxysmal (NPAF) or paroxysmal (PAF), on thromboembolic recurrence. We conducted a systematic review and meta-analysis to describe the impact of AF type on the incidence and risk of thromboembolic recurrence, mortality and major haemorrhage in patients with previous stroke.

Methods: We systematically searched multidisciplinary databases: MEDLINE, EMBASE, CINAHL and Web of Science from inception to December 2018. We selected prospective and retrospective observational studies investigating clinical outcomes in patients with ischaemic stroke and AF, stratified by AF type. We did not include studies on topics other than stroke outcomes in AF patients, unless stroke outcomes were adequately described. We created a random-effects model to generate a pooled estimate of summary event rates for both NPAF and PAF and performed a sensitivity analysis accounting for OAC use post-stroke. We assessed heterogeneity between studies by I2 and visual inspection of funnel plots.

Results: After reviewing 14,127 citations, we selected 108 studies for full text screening. Of these, 23 had the data of interest available from the original report. We contacted authors of the remaining 93 studies and received data from 3 further studies. Hence, we extracted data from a total of 26 studies, reporting outcomes on 23,054 patients. We assessed all included studies for risk of bias (RoB). Overall, RoB was moderate, risk of confounding and survivor bias were notable. The annual incidence rates of thromboembolism in patients with NPAF and PAF were 7.1% (95%CI: 4.2–11.7%) and 5.2% (95%CI: 3.2–8.2%) respectively. The odds ratio (OR) for thromboembolism in patients with NPAF compared to those with PAF was 1.47 (95%CI: 1.08–1.99, p<0.05). The annual mortality rates in patients with NPAF and PAF were 20.0% (95%CI: 13.2– 28.0%) and 10.1% (95%CI: 5.4– 17.3%) respectively. The OR for mortality was 1.90 (95% CI: 1.43–2.52, p<0.001), NPAF versus PAF. There was no difference in rates of major haemorrhage between AF types, OR: 1.01 (95%CI: 0.61–1.69, p=0.97), NPAF versus PAF.

Conclusion: In patients with prior stroke, NPAF is associated with significantly higher risks of thromboembolic recurrence and mortality than PAF. Although current guidelines make no distinction between NPAF and PAF for secondary stroke prevention, future guidance and risk stratification tools may need to consider this differential risk.

PROSPERO: CRD42019118531

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