Background: While anticoagulant and antiplatelet therapies are commonly combined in clinical settings, this combination increases the risk of hemorrhage. However, comparative data on the bleeding risks of different drug combinations remain limited. This study assesses hemorrhage risk associated with various anticoagulant-antiplatelet combinations using data from the USFDA Adverse Event Reporting System (AERS). Methods: Hemorrhage-related reports were extracted from the AERS database (March 2004-June 2024). Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. Disproportionality analysis using frequentist and Bayesian approaches was conducted to detect hemorrhage signals. Results: Out of 160,715 hemorrhage reports, rivaroxaban, warfarin, and apixaban were the most frequently reported anticoagulants, while aspirin and clopidogrel were the top antiplatelets. Apixaban had the lowest reporting odds ratio for hemorrhage. The rivaroxaban-aspirin combination showed the highest hemorrhage risk, while combinations with cilostazol were the lowest. Apixaban, alone and in combination, was associated with reduced hemorrhage and mortality risks. Conclusions: Combining anticoagulants with antiplatelets increases hemorrhage and mortality risk. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for.

Ischemic etiology accounts for two thirds of all strokes in which platelet activation and aggregation play a major role. A variety of antiplatelet therapies have been tested for primary, secondary, and tertiary prevention, with certain patient subtypes benefiting more than others from a specific regimen.

Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase the frequency and severity of bleeding. In this pre-specified analysis, we investigated predictors of bleeding and the association of bleeding with outcome. TARDIS was an international prospective randomised open-label blinded-endpoint trial in participants with ischaemic stroke or TIA within 48 h of onset. Participants were randomised to 30 days of intensive antiplatelet therapy (aspirin, clopidogrel, dipyridamole) or guideline-based therapy (either clopidogrel alone or combined aspirin and dipyridamole). Bleeding was defined using the International Society on Thrombosis and Haemostasis five-level ordered categorical scale: fatal, major, moderate, minor, none. Of 3,096 participants, bleeding severity was: fatal 0.4%, major 1.5%, moderate 1.2%, minor 11.4%, none 85.5%. Major/fatal bleeding was increased with intensive as compared with guideline therapy: 39 vs. 17 participants, adjusted hazard ratio 2.21, 95% CI 1.24-3.93, p = 0.007. Bleeding events diverged between treatment groups in the 8-35 day period but not in the 0-7 or 36-90 day epochs. In multivariate analysis more, and more severe, bleeding events were seen with increasing age, female sex, pre-morbid dependency, increased time to randomisation, prior major bleed, prior antiplatelet therapy and in those randomised to triple vs guideline antiplatelet therapy. More severe bleeding was associated with worse clinical outcomes across multiple physical, emotional and quality of life domains.Trial registration ISRCTN47823388 .

Traumatic brain injury (TBI) is a silent epidemic that has been easily ignored. The safety and efficacy of restarting antiplatelet therapy after encountering traumatic brain injury (TBI) events remain a challenge. We explored the outcomes of restarting aspirin use on secondary stroke and mortality in patients with chronic stroke 4 weeks after suffering from a TBI episode in Taiwan. This study analyzed data from the National Health Insurance Research Database from January 2000 to December 2015. Overall, 136,211 individuals diagnosed with chronic stroke who suffered from acute TBI and received inpatient service were enrolled. The study outcomes were a competing risk of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality. We identified a case group of 15,035 patients with chronic stroke (mean [SD] age of 53.25 [19.74] years; 55.63% male) who restarted aspirin use 4 weeks after suffering from TBI and a control group of 60,140 patients with chronic stroke (mean [SD] age of 53.12 [19.22] years; 55.63% male) who discontinued aspirin use after suffering from TBI. The risk of hospitalization of secondary ischemic stroke [adjusted hazard ratio (aHR) 0.694; 95% confidence interval (CI) 0.621-0.756; P < 0.001] and hemorrhagic stroke (aHR 0.642; 95% CI 0.549-0.723; P < 0.001) and all-cause mortality (aHR 0.840; 95% CI 0.720-0.946; P < 0.001) significantly decreased in patients with chronic stroke restarting aspirin use 1 month after suffering from TBI events (including intracranial hemorrhage) in comparison with the control subjects, regardless of those with or without diabetes mellitus, chronic kidney disease, myocardial infarction, atrial fibrillation, clopidogrel use, and dipyridamole use. Restarting aspirin use could lower the risks of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality in patients with chronic stroke 1 month after suffering from TBI episodes.

Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.

The benefit of using antiplatelet monotherapy in acute ischemic stroke and secondary stroke prevention is well established. In the last few years, several large randomized trials showed that the use of short-term dual antiplatelet therapy in particular stroke subtypes may reduce the risk of recurrent ischemic events. The aim of this article is to provide a critical analysis of the current evidence and recommendations for the use of antiplatelet agents for stroke prevention.

Antiplatelet therapy is key to prevent recurrences in patients with an acute or prior non-cardioembolic stroke or transient ischemic attack (TIA). The narrow balance between the risks of ischemic recurrence and major bleeding is a relevant clinical dilemma in this population.