Optimal Antithrombotic Regimen After Cryptogenic Stroke: A Systematic Review and Network Meta-Analysis

Abstract

Although several antithrombotic strategies have been investigated for the management of cryptogenic strokes, ie, ischemic strokes without known etiologies, an optimal antithrombotic strategy for cryptogenic strokes is unknown. We aim to assess oral antithrombotic agents' comparative efficacy and safety after cryptogenic stroke to identify an optimal treatment.A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and Web of Science until February 2024. We used the random-effects model to report dichotomous outcomes using a risk ratio (RR) with a 95% confidence interval (CI). Frequentist network meta-analysis was conducted using R, version 4.3.1.Seven RCTs with 15,240 patients were included. None of the OACs showed a significant efficacy in preventing all-cause mortality, stroke recurrence, cardiovascular mortality, and major adverse cardiac events compared to aspirin. Also, safety measures were similar between different OACs and aspirin regarding safety measures, including major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]).There was no difference between various OACs and aspirin regarding efficacy and safety outcomes. There is a greater risk of major bleeding with rivaroxaban. Further research is still warranted to define a personalized strategy for selecting antithrombotic strategies after cryptogenic stroke on a case-by-case basis.

Keywords: ESUS; apixaban; aspirin; brain infarct; dabigatran; idiopathic; rivaroxaban; warfarin.

Figure 1.

PRISMA flow chart of the screening process.

Figure 2.

Quality assessment of risk of bias in the included trials. The upper panel presents a schematic representation of risks (low = green, unclear = yellow, and high = red) for specific types of biases of each of the studies in the review. The lower panel presents risks (low = green, unclear = yellow, and high = red) for the subtypes of biases of the combination of studies included in this review.

Figure 3.

Forest and network plots of the efficacy outcomes, comparing warfarin versus DOACs versus aspirin. DOACs: direct oral anticoagulants, MACE: major adverse cardiac events, RR: risk ratio, CI: confidence interval.

Figure 4.

Forest and network plots of the safety outcomes, comparing warfarin versus DOACs versus aspirin. DOACs: direct oral anticoagulants, RR: risk ratio, CI: confidence interval.

Figure 5.

Forest and network plots of the efficacy outcomes, comparing various OACs versus aspirin. OACs: oral anticoagulants, RR: risk ratio, CI: confidence interval.

Figure 6.

Forest and network plots of the safety outcomes, comparing various OACs versus aspirin. OACs: oral anticoagulants, MACE: major adverse cardiac events, RR: risk ratio, CI: confidence interval.