Key result
Intensifying ASCVD antithrombotic therapy links to increased fatal hemorrhage risk but not intracranial bleeding.
Why the study?
The correlation between the magnitude of antithrombotic efficacy and the severity of bleeding risk remains unclear, making the comparative evaluation of antithrombotic regimens challenging.
Does intensive antithrombotic therapy increase bleeding risk compared to less intensive therapy in patients with established ASCVD?
Meta-Analysis (n=357,711)
Does intensive antithrombotic therapy increase bleeding risk compared to less intensive therapy in patients with established ASCVD?
Intensification of antithrombotic therapy for ASCVD prevention is associated with an inevitable increased risk of fatal hemorrhage, even with contemporary regimens.
Intensification warrants caution for fatal hemorrhage risk; confirms bleeding trade-off persists with contemporary ASCVD regimens.
OBJECTIVES: Antithrombotic therapy is a cornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The main drawback of antithrombotic therapy is the associated bleeding risk. The correlation between the magnitude of antithrombotic efficacy and the severity of bleeding risk remains unclear, rendering the comparative evaluation of antithrombotic regimes based on their therapeutic advantages and risks challenging. This study aims to establish a benchmark for evaluating the trade-off between ASCVD prevention and bleeding risk through a systematic analysis of extant trial data. METHODS: Meta-regression analysis. We searched PubMed and Embase and extracted trials comparing antithrombotic treatments in patients with established ASCVD. We extracted data on major adverse cardiovascular events (MACE) reduction and bleeding events. A weighted generalized additive regression was used for data analysis. FINDINGS: Our analysis included 50 studies, comprising a total of 357,711 patients with coronary artery disease (63%), cerebrovascular events (28%) and peripheral arterial disease (15%). Overall, ASCVD event reduction by intensification of antithrombotic therapy correlates with an increased risk of intracranial hemorrhage. Also, the reduction in the composite of ACS and stroke is associated with an increased risk of fatal hemorrhage. When regimens not routinely used in current practice are excluded, the increased risk of intracranial hemorrhage with intensified antithrombotic treatment is attenuated to non-significant, but ASCVD event reduction still correlates with an increased risk in fatal hemorrhage. The analyses and figures we present can serve as a benchmark to compare results of future trials on antithrombotic regimens for ASCVD to other (contemporary) regimens. INTERPRETATION: With currently used antithrombotic regimens, ASCVD event reduction by more intensive treatment no longer increases risk of intracranial bleeding. Fatal hemorrhage remains a seemingly inevitable cost of ASCVD reduction by antithrombotic treatment intensification, albeit at low absolute risks.
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Deurvorst et al. (2025) conducted a meta-analysis in Established atherosclerotic cardiovascular disease (ASCVD) (n=357,711). Intensive antithrombotic therapy vs. Less intensive antithrombotic therapy was evaluated on Major adverse cardiovascular events (MACE) reduction and bleeding events.
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