Oral anticoagulation with or without antiplatelet therapy for secondary stroke prevention in patients with atrial fibrillation and atherosclerosis: a systematic review and meta-analysis

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Ischemic stroke, atrial fibrillation, and atherosclerosis (n=10985). Intervention: Oral anticoagulation plus antiplatelet therapy (OAC + APT) vs. Oral anticoagulation (OAC) monotherapy. Primary outcome: Vascular composite outcome (HR 1.10, 95% CI 0.76–1.58, p=0.62).

Q: What does this research mean for the field?

Adding antiplatelet therapy to oral anticoagulation does not reduce vascular composite events, recurrent stroke, or mortality compared with oral anticoagulation alone in patients with ischemic stroke, atrial fibrillation, and atherosclerosis. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Victor Hugo Pinheiro Lopes; Anderson Matheus Pereira da Silva; Leonardo Januário Campos Cardoso; Gustavo Nascimento de Medeiros; Letícia Gabriela Cavalcante de Freitas; Ocílio Ribeiro Gonçalves; Luisa Medeiros Visentini; Julie de Lima Loiola; Carlos Daniel Santiago Azevedo; Mateus Kist Ibiapino; João Paulo Mota Telles

doi:10.1007/s11239-026-03422-0

November 10, 2026Journal of Thrombosis and ThrombolysisOpen Access

Oral anticoagulation with or without antiplatelet therapy for secondary stroke prevention in patients with atrial fibrillation and atherosclerosis: a systematic review and meta-analysis

View Full Paper

Ask AI

Bookmark

Share

Key result

Adding antiplatelet therapy to OAC shows no benefit over OAC alone for vascular composite outcomes.

HR 1.10
95% CI 0.76–1.58
P=0.62
n=10,985

Why the study?

Patients with ischemic stroke, AF, and atherosclerosis have an increased risk of recurrent ischemic events. Adding antiplatelet therapy to oral anticoagulation may offer protection against these events at the cost of increased bleeding, motivating a comparison of combined therapy versus oral anticoagulation alone.

Does combined oral anticoagulant and antiplatelet therapy reduce the vascular composite outcome and recurrent ischemic stroke compared to oral anticoagulant monotherapy in adult patients with ischemic stroke, atrial fibrillation, and atherosclerosis?

Key Points

To compare the efficacy and safety of combined oral anticoagulation plus antiplatelet therapy versus oral anticoagulation alone for secondary stroke prevention in patients with ischemic stroke, atrial fibrillation, and atherosclerosis.
Systematic review and meta-analysis of PubMed, Embase, and Cochrane Central databases from inception through October 2025 (PROSPERO CRD420251164174).
Included 7 studies (1 randomized controlled trial, 4 retrospective cohorts, and 2 prospective cohorts) encompassing 10,985 adult patients.
Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using random-effects models via restricted maximum likelihood, evaluating RoB 2 and ROBINS-I bias.
Combined therapy showed no significant difference compared to monotherapy for vascular composite outcome (HR 1.10, 95% CI 0.76–1.58; p=0.62) or recurrent ischemic stroke (HR 1.03, 95% CI 0.95–1.12; p=0.51).
Safety outcomes showed no statistically significant differences in major bleeding (HR 1.17, 95% CI 0.94–1.46; p=0.17) or all-cause mortality (HR 0.90, 95% CI 0.68–1.21; p=0.50).

Study Design

Type

Meta-Analysis (n=10,985)

Structured PICO

Does combined oral anticoagulant and antiplatelet therapy reduce the vascular composite outcome and recurrent ischemic stroke compared to oral anticoagulant monotherapy in adult patients with ischemic stroke, atrial fibrillation, and atherosclerosis?

P

Population

10,985 adult patients (mean age 72.5–83.6 years across 7 studies) with ischemic stroke, atrial fibrillation, and concomitant atherosclerosis, followed for 3 months to 4 years.

I

Intervention

Combined antithrombotic therapy consisting of oral anticoagulant therapy (OAC, including NOACs or warfarin) plus antiplatelet therapy (APT / single antiplatelet therapy; n=4,467).

C

Comparator

Oral anticoagulant (OAC) monotherapy (n=6,518).

O

Outcome

Vascular composite outcome, as defined by the individual studies, at the longest available follow-up (ranging from 3 months to 4 years).composite

Main Result

Hazard Ratio: 1.1 (95% CI 0.76–1.58)

p-value: p=0.62

In patients with atrial fibrillation, ischemic stroke, and concomitant atherosclerosis, adding antiplatelet therapy to oral anticoagulation does not reduce recurrent ischemic events or mortality and is associated with higher vascular risk in those with intracranial or extracranial atherosclerosis.

Limitations

Evidence base was composed predominantly of retrospective observational studies, rendering findings susceptible to selection bias, residual confounding, and indication bias.
Substantial clinical and methodological heterogeneity in patient populations, definitions and severity of atherosclerosis, antithrombotic regimens, and follow-up duration.
Risk-of-bias assessments identified at least moderate concerns across studies, and publication bias could not be assessed due to the small number of included studies.
Only one randomized controlled trial contributed data, limiting the overall certainty of evidence.
Substantial clinical and methodological heterogeneity (differences in patient populations, definitions and severity of atherosclerosis, anticoagulant and antiplatelet regimens, and follow-up duration).
Risk-of-bias assessments identified at least moderate concerns across studies, including deviations from intended interventions and incomplete data.
Possibility of publication bias cannot be excluded as funnel plot analysis was not performed due to the small number of studies.
Only one randomized trial contributed data, limiting the overall certainty of evidence.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Does not support adding antiplatelet therapy to OAC; leaves open the need for dedicated RCTs in atherosclerotic subgroups.

Abstract

Background Patients with ischemic stroke (IS), atrial fibrillation (AF), and atherosclerosis have an increased risk of recurrent ischemic events. Addition of antiplatelet therapy (APT) to oral anticoagulant therapy (OAC) may offer additional protection against these events, at the cost of an increased risk of bleeding. This systematic review and meta-analysis aimed to compare the efficacy and safety of combined antithrombotic therapy versus OAC alone in this population. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through October 2025 for randomized controlled trials and observational studies comparing OAC plus APT versus OAC alone in adults with IS, AF, and atherosclerosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed with RoB 2 and ROBINS-I. The protocol was registered in PROSPERO (CRD420251164174). Results Seven studies (4 retrospective, 2 prospective, 1 randomized trial; n = 10,985) were included. Combined therapy was not associated with a reduction in vascular composite outcome (HR 1.10, 95% CI 0.76–1.58), recurrent IS (HR 1.03, 95% CI 0.95–1.12), major bleeding (HR 1.17, 95% CI 0.94–1.46), or all-cause mortality (HR 0.90, 95% CI 0.68–1.21). In the subgroup with intracranial or extracranial atherosclerosis, combined therapy was associated with a significantly higher vascular composite risk (HR 1.67, 95% CI 1.17–2.37). Conclusions Combined antithrombotic therapy with OAC plus APT was not associated with a reduction in recurrent IS, vascular composite outcome, major bleeding, or all-cause mortality in patients with IS, AF, and atherosclerosis. In patients with intracranial or extracranial atherosclerosis, combined therapy was associated with a higher vascular composite risk. These findings suggest that the addition of APT to OAC should be approached with caution in this population, and may be best reserved for select clinical contexts.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Lopes et al. (2026) conducted a meta-analysis in Ischemic stroke, atrial fibrillation, and atherosclerosis (n=10,985). Oral anticoagulation plus antiplatelet therapy (OAC + APT) vs. Oral anticoagulation (OAC) monotherapy was evaluated on Vascular composite outcome (HR 1.10, 95% CI 0.76–1.58, p=0.62). Combined OAC plus antiplatelet therapy did not reduce vascular composite outcomes compared with OAC alone in patients with stroke, AF, and atherosclerosis.

synapsesocial.com/papers/6af502e0d9dbd87f54ece081 https://doi.org/10.1007/s11239-026-03422-0

View Full Paper

Ask AI

Bookmark

Share

Oral anticoagulation with or without antiplatelet therapy for secondary stroke prevention in patients with atrial fibrillation and atherosclerosis: a systematic review and meta-analysis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Oral anticoagulation with or without antiplatelet therapy for secondary stroke prevention in patients with atrial fibrillation and atherosclerosis: a systematic review and meta-analysis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading