Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Norbert Silimon¹, Boudewijn Drop¹, Leander Clénin¹, Krassen Nedeltchev^{1

2}, Timo Kahles², Alexander A Tarnutzer³, Mira Katan⁴, Leo Bonati^{4

5}, Stephan Salmen⁶, Sylvan Albert⁷, Alexander Salerno⁸, Emmanuel Carrera⁹, Christian Berger¹⁰, Nils Peters¹¹, Friedrich Medlin¹², Carlo Cereda¹³, Manuel Bolognese¹⁴, Georg Kägi^{1

15}, Susanne Renaud¹⁶, Julien Niederhauser¹⁷, Christophe Bonvin¹⁸, Michael Schärer¹⁹, Marie-Luise Mono²⁰, Andreas Luft²¹, Biljana Rodic-Tatic²², Urs Fischer^{1

4}, Simon Jung¹, Marcel Arnold¹, Thomas Meinel¹, David Seiffge¹

Affiliations

¹ Department of Neurology, Stroke Research Center Bern, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
² Department of Neurology, Cantonal Hospital of Aarau, Aarau, Switzerland.
³ Department of Neurology, Cantonal Hospital of Baden, Baden, Switzerland.
⁴ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Reha Rheinfelden, Rheinfelden, Switzerland.
⁶ Stroke Unit, Spitalzentrum Biel, Biel, Switzerland.
⁷ Stroke Unit, Cantonal Hospital Graubünden, Chur, Switzerland.
⁸ Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁹ Department of Neurology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
¹⁰ Stroke Unit, Cantonal Hospital Grabs, Switzerland.
¹¹ Stroke Center, Klinik Hirslanden, Zürich, Switzerland.
¹² Stroke Unit, Cantonal Hospital Fribourg, Fribourg, Switzerland.
¹³ Stroke Center, Neurocenter of Southern Switzerland, Lugano, Switzerland.
¹⁴ Neurocenter, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
¹⁶ Neurology and Stroke Unit, Neuchâtel Hospital Network, Neuchâtel, Switzerland.
¹⁷ Stroke Unit, Groupement hospitalier de l'ouest lémanique, Nyon, Switzerland.
¹⁸ Stroke Unit, Hôpital du Valais, Sion, Switzerland.
¹⁹ Stroke Unit, Bürgerspital Solothurn, Solothurn, Switzerland.
²⁰ Stroke Unit, Stadtspital Triemli, Zurich, Switzerland.
²¹ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
²² Stroke Unit, Cantonal Hospital Winterthur, Winterthur, Switzerland.

PMID: 37622482
PMCID: PMC10472957
DOI: 10.1177/23969873231174942

Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Norbert Silimon et al. Eur Stroke J. 2023 Sep.

. 2023 Sep;8(3):692-702.

doi: 10.1177/23969873231174942. Epub 2023 May 24.

Authors

Affiliations

¹ Department of Neurology, Stroke Research Center Bern, Inselspital University Hospital Bern and University of Bern, Bern, Switzerland.
² Department of Neurology, Cantonal Hospital of Aarau, Aarau, Switzerland.
³ Department of Neurology, Cantonal Hospital of Baden, Baden, Switzerland.
⁴ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Reha Rheinfelden, Rheinfelden, Switzerland.
⁶ Stroke Unit, Spitalzentrum Biel, Biel, Switzerland.
⁷ Stroke Unit, Cantonal Hospital Graubünden, Chur, Switzerland.
⁸ Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁹ Department of Neurology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
¹⁰ Stroke Unit, Cantonal Hospital Grabs, Switzerland.
¹¹ Stroke Center, Klinik Hirslanden, Zürich, Switzerland.
¹² Stroke Unit, Cantonal Hospital Fribourg, Fribourg, Switzerland.
¹³ Stroke Center, Neurocenter of Southern Switzerland, Lugano, Switzerland.
¹⁴ Neurocenter, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
¹⁶ Neurology and Stroke Unit, Neuchâtel Hospital Network, Neuchâtel, Switzerland.
¹⁷ Stroke Unit, Groupement hospitalier de l'ouest lémanique, Nyon, Switzerland.
¹⁸ Stroke Unit, Hôpital du Valais, Sion, Switzerland.
¹⁹ Stroke Unit, Bürgerspital Solothurn, Solothurn, Switzerland.
²⁰ Stroke Unit, Stadtspital Triemli, Zurich, Switzerland.
²¹ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
²² Stroke Unit, Cantonal Hospital Winterthur, Winterthur, Switzerland.

PMID: 37622482
PMCID: PMC10472957
DOI: 10.1177/23969873231174942

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.

Keywords: Acute ischaemic stroke; aetiology; anticoagulation; antiplatelet therapy; functional outcome; incidence; recurrent stroke; stroke severity.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AAT reported consultant and/or speaker fees from Mitsubishi Tanabe Pharma, Medtronic, AstraZeneca and Schwabe Pharma outside the submitted work. MK received research grants from the Swiss National Science Foundation (NR 182267; NR 204977; NR 198783), the Swiss Heart Foundation; the USZ-Foundation and has received nonfinancial support from B.R.A.H.M.S. Thermofisher Scientific as well as ROCHE Diagnostics, none related to this study. MK has served on the advisory board of Medtronic, Astra Zeneca, BMS/Pfizer and Bayer. MB reported consultant fees from Astra Zeneca and Sandoz outside the submitted work. TRM reported grants from Bangerter Rhyner Foundation, Swiss Heart Foundation and Swiss National Science Foundation outside the submitted work. DJS reported grants from Bangerter Rhyner Foundation and Swiss Heart Foundation outside the study; personal fees from Bayer, Alexion and VarmX outside the submitted work. No other disclosures/conflicts of interest were reported.

Figures

**Figure 1.**
Flow diagram of the study population. ICH: intracerebral haemorrhage; mRS: modified Rankin scale; N: number of patients; NIHSS: National Institutes of Health Stroke Scale.

**Figure 2.**
Antithrombotic therapy by case year in the overall population (a) and in patients with history of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) (b). AC: anticoagulation; APT: antiplatelet therapy.

**Figure 3.**
Stroke aetiologies (modified TOAST) according to pre-stroke antithrombotic treatment. AC: anticoagulation; APT: antiplatelet therapy; ATT: antithrombotic treatment; PFO: patent foramen ovale.

See this image and copyright information in PMC

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Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Affiliations

Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances