Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2025 Apr;32(4):e70163.
doi: 10.1111/ene.70163.

Real-World Dual Antiplatelet Therapy Use Exceeds Randomized Trials Boundaries With Possible Safety Issues in Patients With Large Artery Atherosclerosis-Insights From the READAPT Study

Eleonora De Matteis  1 Federico De Santis  2 Matteo Foschi  2 Michele Romoli  3 Tiziana Tassinari  4 Valentina Saia  4 Silvia Cenciarelli  5 Chiara Bedetti  5 Chiara Padiglioni  5 Bruno Censori  6 Valentina Puglisi  6 Luisa Vinciguerra  6 Maria Guarino  7 Valentina Barone  7 Marialuisa Zedde  8 Ilaria Grisendi  8 Ilaria Maestrini  9 Maria Rosaria Bagnato  9 Marco Petruzzellis  10 Domenico Maria Mezzapesa  10 Pietro Di Viesti  11 Vincenzo Inchingolo  11 Manuel Cappellari  12 Mara Zenorini  12 Paolo Candelaresi  13 Vincenzo Andreone  13 Giuseppe Rinaldi  14 Alessandra Bavaro  14 Anna Cavallini  15 Stefan Moraru  15 Maria Grazia Piscaglia  16 Valeria Terruso  17 Marina Mannino  17 Alessandro Pezzini  18   19 Giovanni Frisullo  20 Francesco Muscia  21 Maurizio Paciaroni  22 Maria Giulia Mosconi  23 Andrea Zini  24 Ruggiero Leone  25 Carmela Palmieri  26 Letizia Maria Cupini  27 Michela Marcon  28 Rossana Tassi  29 Enzo Sanzaro  30 Cristina Paci  31 Giovanna Viticchi  32 Daniele Orsucci  33 Anne Falcou  34 Susanna Diamanti  35 Roberto Tarletti  36 Patrizia Nencini  37 Eugenia Rota  38 Federica Nicoletta Sepe  39 Delfina Ferrandi  39 Luigi Caputi  40 Gino Volpi  41 Salvatore La Spada  42 Mario Beccia  43 Claudia Rinaldi  44 Vincenzo Mastrangelo  44 Francesco Di Blasio  45 Paolo Invernizzi  46 Giuseppe Pelliccioni  47 Maria Vittoria De Angelis  45   48 Laura Bonanni  49 Giampietro Ruzza  50 Emanuele Alessandro Caggia  51 Monia Russo  52 Agnese Tonon  53 Maria Cristina Acciarri  54 Sabrina Anticoli  55 Cinzia Roberti  56 Giovanni Manobianca  57 Gaspare Scaglione  57 Francesca Pistoia  2 Alberto Fortini  58 Antonella De Boni  59 Alessandra Sanna  60 Alberto Chiti  61 Leonardo Barbarini  62 Marcella Caggiula  62 Maela Masato  63 Massimo Del Sette  64 Francesco Passarelli  65 Maria Roberta Bongioanni  66 Danilo Toni  67 Stefano Ricci  5   68 Simona Sacco  2 Raffaele Ornello  2 READAPT Study Group
Collaborators, Affiliations
Observational Study

Real-World Dual Antiplatelet Therapy Use Exceeds Randomized Trials Boundaries With Possible Safety Issues in Patients With Large Artery Atherosclerosis-Insights From the READAPT Study

Eleonora De Matteis et al. Eur J Neurol. 2025 Apr.

Abstract

Background and aim: According to randomized controlled trials (RCTs), dual antiplatelet therapy (DAPT) is more effective for secondary prevention of ischemic events attributable to large artery atherosclerosis (LAA) than other mechanisms. We investigated whether real-world application may impact DAPT effectiveness and safety in the REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT, NCT05476081).

Methods: READAPT was an observational multicenter study including patients with minor ischemic stroke or TIA treated with short-term DAPT. At 90 days, we assessed primary effectiveness (ischemic recurrence, severe bleeding, or vascular death) and safety (severe to moderate bleeding) outcomes. We explored associations between LAA and outcomes using Cox regression. Within patients with and without LAA, outcomes were compared between subgroups based on age, NIHSS score (for ischemic stroke patients), ABCD2 score (for TIA patients), presence and number of MRI acute lesions, and DAPT regimen characteristics.

Results: Among 1920 analyzed patients (of 2278 enrolled), 452 had LAA. Unlike RCTs, 21.2% of patients with LAA had NIHSS > 5, and 48.2% received DAPT > 30 days. Patients with LAA had higher bleeding rates (3.5% vs. 2.1%, p = 0.004), primarily hemorrhagic infarctions and moderate bleeding, than those without LAA. However, primary effectiveness outcomes were similar (4.9% vs. 3.5%, p = 0.201) between the groups. In patients with LAA, prolonged DAPT (> 21 days), multiple MRI lesions, age ≥ 65, and loading doses increased bleeding risk.

Conclusions: The real-world DAPT use in patients with LAA exceeds RCTs boundaries with possible drawbacks on treatment safety.

Keywords: TIA; dual antiplatelet therapy; large artery atherosclerosis; minor ischemic stroke; real world.

PubMed Disclaimer

Conflict of interest statement

A.Z. reports compensation from Angels Initiative, Boehringer‐Ingelheim, Daiichi Sankyo, CSL Behring, Bayer, and Astra Zeneca; and he is a member of ESO guidelines, ISA‐AII guidelines, and IRETAS steering committee. R.O. reports compensations from Novartis and Allergan, Teva Pharmaceutical Industries, Eli Lilly and Company. S.S. reports compensations from Novartis, NovoNordisk, Allergan, AstraZeneca, Pfizer Canada Inc., Eli Lilly and Company, Teva Pharmaceutical Industries, H. Lundbeck A/S, and Abbott Canada; employment by Università degli Studi dell'Aquila. M.Pa. reports compensation from Daiichi Sankyo Company, Bristol Myers Squibb, Bayer, and Pfizer Canada Inc. D.T. reports compensation from Alexion, AstraZeneca, Medtronic, and Pfizer. The other authors report no conflicts.

Figures

FIGURE 1
FIGURE 1
Consolidated standards of reporting trials diagram of enrolment in the study. LAA, large‐artery atherothrombosis; FU, follow‐up.
FIGURE 2
FIGURE 2
Presence of ipsilateral extracranial stenosis, symptomatic intracranial stenosis, and/or aortic plaque in patients with an index event attributable to large‐artery atherosclerosis. N, number.
FIGURE 3
FIGURE 3
Number of MRI lesions in patients with large‐artery atherosclerosis (A) and with non‐large‐artery atherosclerosis (B). LAA, large‐artery atherosclerosis, N, number.
FIGURE 4
FIGURE 4
Primary effectiveness outcome and any bleeding in patients with large‐artery atherosclerosis and with non‐large‐artery atherosclerosis. LAA, large‐artery atherosclerosis.
FIGURE 5
FIGURE 5
Comparison of primary effectiveness outcome (A) and any bleeding (B) between patients with large‐artery atherosclerosis and non‐large‐artery atherosclerosis across pre‐specified subgroups of interest. BMI, body mass index; DAPT, dual antiplatelet therapy; LAA, large‐artery atherosclerosis; NIHSS, National Institutes of Health Stroke Scale.

Similar articles

  • Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.
    De Matteis E, Ornello R, De Santis F, Foschi M, Romoli M, Tassinari T, Saia V, Cenciarelli S, Bedetti C, Padiglioni C, Censori B, Puglisi V, Vinciguerra L, Guarino M, Barone V, Zedde M, Grisendi I, Diomedi M, Bagnato MR, Petruzzellis M, Mezzapesa DM, Di Viesti P, Inchingolo V, Cappellari M, Zenorini M, Candelaresi P, Andreone V, Rinaldi G, Bavaro A, Cavallini A, Moraru S, Querzani P, Terruso V, Mannino M, Pezzini A, Frisullo G, Muscia F, Paciaroni M, Mosconi MG, Zini A, Leone R, Palmieri C, Cupini LM, Marcon M, Tassi R, Sanzaro E, Paci C, Viticchi G, Orsucci D, Falcou A, Diamanti S, Tarletti R, Nencini P, Rota E, Sepe FN, Ferrandi D, Caputi L, Volpi G, Spada S, Beccia M, Rinaldi C, Mastrangelo V, Di Blasio F, Invernizzi P, Pelliccioni G, De Angelis MV, Bonanni L, Ruzza G, Caggia EA, Russo M, Tonon A, Acciarri MC, Anticoli S, Roberti C, Manobianca G, Scaglione G, Pistoia F, Fortini A, De Boni A, Sanna A, Chiti A, Barbarini L, Caggiula M, Masato M, Del Sette M, Passarelli F, Roberta Bongioanni M, Toni D, Ricci S, Sacco S. De Matteis E, et al. Eur Stroke J. 2024 Dec;9(4):989-999. doi: 10.1177/23969873241255250. Epub 2024 Jun 13. Eur Stroke J. 2024. PMID: 38869034 Free PMC article.
  • Exploring Sex Differences in Outcomes of Dual Antiplatelet Therapy for Patients With Noncardioembolic Mild-to-Moderate Ischemic Stroke or High-Risk Transient Ischemic Attack: A Propensity-Matched Analysis of the READAPT Study Cohort.
    Foschi M, D'Anna L, De Matteis E, De Santis F, Romoli M, Tassinari T, Saia V, Cenciarelli S, Bedetti C, Padiglioni C, Censori B, Puglisi V, Vinciguerra L, Guarino M, Barone V, Zedde M, Grisendi I, Diomedi M, Bagnato MR, Petruzzellis M, Mezzapesa DM, Di Viesti P, Inchingolo V, Cappellari M, Zivelonghi C, Candelaresi P, Andreone V, Rinaldi G, Bavaro A, Cavallini A, Moraru S, Piscaglia MG, Terruso V, Mannino M, Pezzini A, Frisullo G, Muscia F, Paciaroni M, Mosconi MG, Zini A, Leone R, Palmieri C, Cupini LM, Marcon M, Tassi R, Sanzaro E, Papiri G, Paci C, Viticchi G, Orsucci D, Falcou A, Beretta S, Tarletti R, Nencini P, Rota E, Sepe FN, Ferrandi D, Caputi L, Volpi G, La Spada S, Beccia M, Rinaldi C, Mastrangelo V, Di Blasio F, Invernizzi P, Pelliccioni G, De Angelis MV, Bonanni L, Ruzza G, Caggia EA, Russo M, Tonon A, Acciarri MC, Anticoli S, Roberti C, Manobianca G, Scaglione G, Pistoia F, Fortini A, De Boni A, Sanna A, Chiti A, Barbarini L, Caggiula M, Masato M, Del Sette M, Passarelli F, Bongioanni MR, De Michele M, Ricci S, Ornello R, Sacco S; READAPT Study Group. Foschi M, et al. Stroke. 2025 Feb;56(2):305-317. doi: 10.1161/STROKEAHA.124.049210. Epub 2024 Dec 9. Stroke. 2025. PMID: 39648888
  • Real-world comparison of dual versus single antiplatelet treatment in patients with non-cardioembolic mild-to-moderate ischemic stroke: A propensity matched analysis.
    Foschi M, Ornello R, D'Anna L, De Matteis E, De Santis F, Barone V, Viola M, Mosconi MG, Rosin D, Romoli M, Tassinari T, Cenciarelli S, Censori B, Zedde M, Diomedi M, Petruzzellis M, Inchingolo V, Cappellari M, Candelaresi P, Bavaro A, Cavallini A, Piscaglia MG, Terruso V, Pezzini A, Frisullo G, Muscia F, Zini A, Leone R, Palmieri C, Cupini LM, Marcon M, Tassi R, Sanzaro E, Papiri G, Viticchi G, Orsucci D, Falcou A, Diamanti S, Tarletti R, Nencini P, Rota E, Sepe FN, Caputi L, Volpi G, La Spada S, Beccia M, Mastrangelo V, Invernizzi P, Pelliccioni G, De Angelis MV, Bonanni L, Ruzza G, Caggia EA, Russo M, Tonon A, Acciarri MC, Anticoli S, Roberti C, Scaglione G, Pistoia F, Alessi C, De Boni A, Sanna A, Chiti A, Barbarini L, Masato M, Del Sette M, Passarelli F, Bongioanni MR, De Michele M, Ricci S, Valente M, Gigli GL, Merlino G, Paciaroni M, Guarino M, Sacco S. Foschi M, et al. Int J Stroke. 2025 Apr;20(4):438-449. doi: 10.1177/17474930241302991. Epub 2024 Dec 16. Int J Stroke. 2025. PMID: 39555606
  • Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials.
    Bhatia K, Jain V, Aggarwal D, Vaduganathan M, Arora S, Hussain Z, Uberoi G, Tafur A, Zhang C, Ricciardi M, Qamar A. Bhatia K, et al. Stroke. 2021 Jun;52(6):e217-e223. doi: 10.1161/STROKEAHA.120.033033. Epub 2021 Apr 27. Stroke. 2021. PMID: 33902301
  • Efficacy and safety of dual versus mono antiplatelet therapy in patients with stroke or transient ischemic attack: An updated meta-analysis of 18 randomized controlled trials.
    Fu-Sang W, Xiao-Han Z, Yang Z, Ting-Ting C, Chao S, Jing-Yi L, Jian-Jun Z. Fu-Sang W, et al. Pharmazie. 2020 Oct 1;75(10):516-523. doi: 10.1691/ph.2020.0683. Pharmazie. 2020. PMID: 33305729 Review.

References

    1. Kolominsky‐Rabas P. L., Weber M., Gefeller O., Neundoerfer B., and Heuschmann P. U., “Epidemiology of Ischemic Stroke Subtypes According to TOAST Criteria: Incidence, Recurrence, and Long‐Term Survival in Ischemic Stroke Subtypes: A Population‐Based Study,” Stroke 32, no. 12 (2001): 2735–2740, 10.1161/hs1201.100209. - DOI - PubMed
    1. White H., Boden‐Albala B., Wang C., et al., “Ischemic Stroke Subtype Incidence Among Whites, Blacks, and Hispanics: The Northern Manhattan Study,” Circulation 111, no. 10 (2005): 1327–1331, 10.1161/01.Cir.0000157736.19739.D0. - DOI - PubMed
    1. Flach C., Muruet W., Wolfe C. D. A., Bhalla A., and Douiri A., “Risk and Secondary Prevention of Stroke Recurrence: A Population‐Base Cohort Study,” Stroke 51, no. 8 (2020): 2435–2444, 10.1161/strokeaha.120.028992. - DOI - PMC - PubMed
    1. Bulwa Z., Saleh Velez F. G., Brorson J. R., and Pinto C. B., “Ipsilateral Nonstenotic Carotid Disease in Minor Ischemic Stroke: An Exploratory Analysis of the POINT Randomized Clinical Trial,” Journal of Stroke and Cerebrovascular Diseases 29, no. 11 (2020): 105115, 10.1016/j.jstrokecerebrovasdis.2020.105115. - DOI - PubMed
    1. Liu L., Wong K. S., Leng X., et al., “Dual Antiplatelet Therapy in Stroke and ICAS: Subgroup Analysis of CHANCE,” Neurology 85, no. 13 (2015): 1154–1162, 10.1212/WNL.0000000000001972. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

Associated data