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Active factor XI is associated with the risk of cardiovascular events in stable coronary artery disease patients
Elżbieta Paszek1, Elżbieta Pociask2, Michał Ząbczyk3
1Clinical Department of Interventional Cardiology, John Paul II Hospital, 31-202, Krakow, Poland.
Insights
Activated factor XI (FXIa) predicts major cardiovascular events in stable coronary artery disease (CAD) patients. This finding supports FXIa inhibitors as potential new treatments for preventing arterial thromboembolism.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Thrombosis Research
Background:
- Tissue factor (TF) and activated factor XI (FXIa) are implicated in thrombotic events.
- Their role in stable coronary artery disease (CAD) outcomes is not well understood.
- This study investigates the predictive value of TF and FXIa in long-term CAD patient observation.
Purpose of the Study:
- To determine if circulating active TF and FXIa are associated with clinical outcomes in stable CAD patients.
- To assess the long-term predictive value of these factors for major adverse cardiovascular events.
Main Methods:
- Assessed active TF and FXIa via thrombin generation response in 124 stable multivessel CAD patients.
- Recorded a composite endpoint of myocardial infarction, stroke, systemic thromboembolism, and cardiovascular death.
- Followed patients for a median of 106 months.
Main Results:
- Circulating FXIa and active TF were detected in 40% and 20.8% of patients, respectively.
- Detectable FXIa and active TF at baseline were associated with a higher frequency of the composite endpoint (HR 6.21 and 4.02, respectively).
- Multivariate analysis identified FXIa, but not active TF, as an independent predictor of adverse cardiovascular events.
Conclusions:
- Circulating FXIa is a significant predictor of arterial thromboembolic events in advanced CAD.
- This finding supports the development of FXIa inhibitors as novel antithrombotic therapies.
- Highlights the potential of targeting FXIa for preventing cardiovascular events in CAD.
Background And Aims:
Tissue factor (TF) and activated factor XI (FXIa) have been associated with acute coronary syndrome, ischemic stroke and venous thromboembolism. Their predictive value in stable coronary artery disease (CAD) is unclear. We investigated whether active TF and FXIa were associated with clinical outcomes in CAD patients in long-term observation.
Methods:
In 124 stable patients with multivessel CAD, we assessed the presence of circulating, active TF and FXIa by measuring a response of thrombin generation to respective inhibitory antibodies. We recorded the composite endpoint of myocardial infarction (MI), stroke, systemic thromboembolism and cardiovascular death during follow-up (median 106 months, interquartile range 95-119).
Results:
Circulating FXIa and active TF were detected in 40% and 20.8% of the 120 patients (aged 65.0 [57.0-70.3] years, men, 78.3%), who completed follow-up. The composite endpoint occurred more frequently in patients with detectable active TF and FXIa present at baseline (hazard ratio [HR] 4.02, 95% confidence interval [CI] 2.26-7.17, p < 0.001 and HR 6.21, 95% CI 3.40-11.40, p < 0.001, respectively). On multivariate analysis FXIa, but not active TF, was an independent predictor of the composite endpoint, as well as MI, stroke/systemic thromboembolism, and cardiovascular death, when analyzed separately.
Conclusions:
To our knowledge, this study is the first to show that circulating FXIa predicts arterial thromboembolic events in advanced CAD, supporting a growing interest in FXIa inhibitors as novel antithrombotic agents.
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