Effect of prior antiplatelet therapy on large vessel occlusion in patients with non-valvular atrial fibrillation newly initiated on apixaban

https://doi.org/10.1016/j.jns.2021.117603Get rights and content

Highlights

  • Antiplatelet therapy for large vessel occlusion was associated with major bleeding.

  • Major bleeding was more common in the antiplatelet group without IVT.

  • Ischemic events and 30-day all-cause mortality were similar between the groups.

Abstract

Introduction

We evaluated the effect of prior antiplatelet therapy on large vessel occlusion (LVO) in patients with non-valvular atrial fibrillation (NVAF) newly initiated on apixaban.

Methods

Patients with acute LVO with acute stroke due to NVAF or stenosis with NVAF started on apixaban within 14 days of onset were enrolled. We compared incidence of major bleeding, cerebral hemorrhage, ischemic events, cerebral infarction, and all-cause mortality between patients with and without prior antiplatelet therapy for acute LVO. We also compared these events between patients who continued antiplatelet therapy after onset (continued group) and those who discontinued it (discontinued group). Hazard ratios were estimated after adjusting for confounders; interaction was evaluated considering intravenous thrombolysis (IVT) or endovascular treatment (EVT) according to major bleeding.

Results

The study comprised 686 eligible patients (excluded [n = 194]; enrolled [n = 492]). The antiplatelet group consisted of older patients (mean: 79 vs. 76 years; p = 0.006) and had a higher cumulative incidence of major bleeding (7.3% vs. 2.9%, p = 0.003). The incidence of ischemic events and all-cause mortality was similar between the groups. Among the 109 patients in the antiplatelet group, the cumulative incidence of major bleeding, ischemic events, and all-cause mortality was comparable between continued group (n = 26) and discontinued group (n = 83). There were no significant differences between groups with and without IVT/EVT. However, major bleeding occured more frequently in the antiplatelet group without IVT.

Conclusion

Prior antiplatelet therapy for LVO in patients with NVAF newly initiated on apixaban was associated with major bleeding, which was more frequent in the antiplatelet group without IVT.

Introduction

Antiplatelet drugs are widely recommended for the secondary prevention of atherosclerotic diseases, including cardiovascular and cerebrovascular diseases. However, it has also been reported that prior antiplatelet therapy increases the risk of bleeding complications [1]. The RELAXED study, in which patients with acute ischemic stroke received direct oral anticoagulant (DOAC) therapy with rivaroxaban due to non-valvular atrial fibrillation (NVAF), demonstrated that major bleeding within 90 days was associated with the use of antiplatelet therapy before onset [2]. However, the effect of prior antiplatelet therapy in patients with acute large vessel occlusion (LVO) who received DOAC therapy due to NVAF has not been well studied. Previous reports have shown that prior antiplatelet therapy was not a decisive factor in the development of cerebral hemorrhage after intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in patients who developed LVO [[3], [4], [5], [6], [7]]. Thus, in this study, we evaluated the effect of prior antiplatelet therapy on LVO in patients with NVAF newly initiated on apixaban in clinical practice.

Section snippets

Study design and patients

This was a post-hoc analysis of data collected from the Acute Large Vessel Occlusion Registry, a historical, prospective, multicenter registry of Japanese patients with acute stroke with LVO due to NVAF, including those with peripheral arterial occlusion or ≥ 50% stenosis on cerebral angiography, computed tomography (CT) angiography or magnetic resonance angiography, such as M2–3 segment middle cerebral artery, A1–2 segment anterior cerebral artery, or P1–2 segment posterior cerebral artery and

Patient characteristics

Of the 713 patients enrolled in the registry, 686 were eligible for this study. In total, 492 patients were included in this study (Fig. 1). There were 109 and 383 patients in the antiplatelet and no antiplatelet groups, respectively. In the antiplatelet group, the antiplatelet drugs used were aspirin, cilostazol, clopidogrel, prasugrel, and ticlopidine in 81 (74%), 9 (8.3%), 19 (17%), 1 (0.9%), and 1 (0.9%) patient(s), respectively (Table 1). Patients in the antiplatelet group were

Discussion

This study showed that antiplatelet therapy prior to acute stroke due to LVO was significantly associated with major bleeding within 30 days after onset. Notably, major bleeding was more frequently observed in the antiplatelet group without IVT. However, major bleeding was not significantly associated with cerebral hemorrhage. In this regard, our results were similar to those of the RELAXED study, which demonstrated that major bleeding within 90 days was associated with prior antiplatelet

Conclusions

Prior antiplatelet therapy for LVO in patients with NVAF newly initiated on apixaban was associated with major bleeding within 30 days. Notably, major bleeding was more frequent in the antiplatelet group without IVT. However, the incidence of ischemic events and all-cause mortality were similar between the two groups.

The following is the supplementary data related to this article.

Funding

This work was supported by Bristol-Myers Squibb, Japan. The funding source did not have any role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Data statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declaration of Competing Interest

Dr. Yoshimura reports research grants from Bristol-Myers Squibb and lecture fees from Boehringer Ingelheim, Daiichi Sankyo, Bayer, Pfizer, and Bristol-Myers Squibb. Dr. Uchida reports lecture fees from Daiichi Sankyo. Dr. Sakai reports research grants from NeuroVasc, Daiichi Sankyo, Medtronic, and Terumo and lecture fees from Asahi-Intec, Daiichi Sankyo, Medtronic, and Stryker. Dr. Yamagami reports research grants from Bristol-Myers Squibb; lecture fees from Bayer, Daiichi Sankyo, Bristol-Myers

Acknowledgments

Ethics approval: The Institutional Review Boards of all 38 participating centers approved the study protocol.

Consent to participate: Written informed consent was obtained from the prospectively registered patients and from an opt-out method from the retrospectively registered patients. This method was approved by the Institutional Review Boards in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan.

Consent for publication: Consent for

References (27)

  • A. Pandhi et al.

    Antiplatelet pretreatment and outcomes following mechanical thrombectomy for emergent large vessel occlusion strokes

    J. Neurointerv. Surg.

    (2018)
  • G. Merlino et al.

    Prior use of antiplatelet therapy and outcomes after endovascular therapy in acute ischemic stroke due to large vessel occlusion: a single-center experience

    J. Clin. Med.

    (2018)
  • R.A. van de Graaf et al.

    MR CLEAN registry investigators, prior antiplatelet therapy in patients undergoing endovascular treatment for acute ischemic stroke: results from the MR CLEAN registry

    Int. J. Stroke

    (2021)
  • Cited by (0)

    View full text