Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

So ask your doctor what else needs to be done to prevent that next stroke. I'm doing a daily 325 aspirin, hopefully that's good enough for me.

Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Norbert Silimon https://orcid.org/0009-0001-5431-422X, Boudewijn Drop https://orcid.org/0000-0002-3415-6834, […], and David Seiffge https://orcid.org/0000-0003-3890-3849 david.seiffge@insel.ch+27View all authors and affiliations

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https://doi.org/10.1177/23969873231174942

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Abstract

Background:

Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT.

Methods:

In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3–6) and recurrent ischaemic stroke at 3 months using regression models.

Results:

Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA (n = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% (n = 3416), cardiac embolism in 23.6% (n = 4059), small vessel disease in 11.7% (n = 2011), other causes in 7.4% (n = 1267), more than one cause in 6.3% (n = 1078) and unknown cause in 31.3% (n = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98–1.14; p = 0.135) or death (aOR = 1.10; 95% CI: 0.99–1.21; p = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11–1.44; p < 0.001).

Conclusions:

One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.

Introduction

Antiplatelet therapy (APT) is the cornerstone of primary and secondary prevention of a variety of cardiovascular conditions including secondary prevention of non-cardioembolic stroke and transient ischaemic attack.¹ Aspirin, in particular, is a well-established antiplatelet agent that reduces the overall cardiovascular risk in secondary prevention of cardiovascular disease and cerebrovascular events by about a fifth to a quarter per year.^2,3 However, strokes do (re-) occur despite APT with a yearly risk of around 3%–4% after the index event. In the US, approximately 185,000 (23%) of the 795,000 incident ischaemic strokes each year are recurrent strokes.⁴ It is estimated that about one-third to one-half of these strokes occur while on APT.⁴ Furthermore, about one-third of ischaemic strokes in patients with atrial fibrillation occurs while on oral anticoagulation (AC)^5,6 and there has been a number of recent studies on ischaemic stroke despite anticoagulant therapy elucidating aetiology, risk of recurrent stroke and secondary prevention strategies.^7,8

Data from a large, national stroke registry in a health care setting with universal coverage and without major barriers for acute stroke treatment and secondary prevention therapies may help to characterise this problem and provide the groundwork for future studies assessing specific diagnostic and therapeutic interventions for this vulnerable population.

The aim of this study was to explore and characterise ‘breakthrough’ ischaemic strokes occurring despite APT both in the overall population and in patients with a history of ischaemic stroke or transient ischaemic attack. We thought to assess frequency, aetiology, clinical characteristics and outcomes, including functional outcome, recurrent strokes, intracranial haemorrhage and death in patients who had ischaemic stroke despite APT using data from a large, prospective national stroke registry.

 

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