Real-world comparison of dual versus single antiplatelet treatment in patients with non-cardioembolic mild-to-moderate ischemic stroke: A propensity matched analysis

Abstract

Background:

Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk transient ischemic attack (TIA). As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population.

Methods:

Post hoc analysis of prospectively collected data from the READAPT cohort and three prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale (NIHSS) score 0–10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24 h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage.

Results:

We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% vs. 84.4%, risk difference 3.1% (95% confidence interval (CI): 0.1%–6.1%); p = 0.047, risk ratio 1.03 (95% CI: 1.01–1.07); p = 0.043) and higher rate of 24-h early neurological improvement (25.3% vs. 15.4%, risk difference 9.9% (95% CI: 6.4%–13.4%); p < 0.001, risk ratio 1.65 (95% CI: 1.37–1.97); p < 0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis, and those who received antiplatelet loading dose.

Conclusion:

Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real world and in patients who do not strictly fulfill the criteria of landmark large clinical trials.

Keywords

Ischemic stroke dual antiplatelet treatment aspirin outcomes prognosis mild-to-moderate

Get full access to this article

View all access options for this article.

References

Wang

Zhao

, et al Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013; 369: 11–19.

Johnston

Easton

Farrant

, et al Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018; 379: 215–225.

Johnston

Amarenco

Denison

, et al Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med 2020; 383: 207–217.

Wang

Meng

Wang

, et al Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA. N Engl J Med 2021; 385: 2520–2530.

De Matteis

De Santis

Ornello

, et al Divergence between clinical trial evidence and actual practice in use of dual antiplatelet therapy after transient ischemic attack and minor stroke. Stroke 2023; 54: 1172–1181.

De Matteis

Ornello

De Santis

, et al Beyond RCTs: short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack. Eur Stroke J 9: 989-999.

Chen

Cui

Wang

, et al Clopidogrel plus aspirin vs aspirin alone in patients with acute mild to moderate stroke: the ATAMIS randomized clinical trial. JAMA Neurol 2024; 81: 450–460.

Silvestrelli

Corea

Paciaroni

, et al The Perugia hospital-based stroke registry: report of the 2nd year. Clin Exp Hypertens 2002; 24: 485–491.

Guarino

Rondelli

Favaretto

, et al Short- and long-term stroke risk after urgent management of transient ischaemic attack: the Bologna TIA clinical pathway. Eur Neurol 2015; 74: 1–7.

10.

Merlino

Nesi

Vergobbi

, et al The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling. Front Neurol 2023; 14: 1212712.

11.

Kleindorfer

Towfighi

Chaturvedi

, et al 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke 2021; 52: e364–e467.

12.

Dawson

Béjot

Christensen

, et al European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack. Eur Stroke J 2022; 7: I–II.

13.

Von Kummer

Broderick

Campbell

, et al The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke 2015; 46: 2981–2986.

14.

Stuart

EA.

Matching methods for causal inference: a review and a look forward. Stat Sci 2010; 25: 1–21.

15.

Chan

BPL

Wong

LYH

Tan

BYQ

Yeo

Venketasubramanian

Dual antiplatelet therapy for the acute management and long-term secondary prevention of ischemic stroke and transient ischemic attack, an updated review. J Cardiovasc Dev Dis 2024; 11: 48.

16.

Xia

Zhang

, et al Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke. J Clin Neurosci 2015; 22: 83–86.

17.

Zhou

Wang

Lin

Chai

Aspirin plus clopidogrel may reduce the risk of early neurologic deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles. J Neurol 2018; 265: 2396–2403.

18.

Ornello

Foschi

De Santis

, et al Combining intravenous thrombolysis and dual antiplatelet treatment in patients with minor ischemic stroke: a propensity matched analysis of the READAPT study cohort. J Am Heart Assoc 2024; 13: e036275.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.51 MB

0.02 MB