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Factor XI as a new target for prevention of thromboembolism in cardiovascular disease: a meta-analysis of randomized controlled trials

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Abstract

Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease. The use of conventional anticoagulants carries potential side effects, mainly bleeding. Drugs targeting Factor XI (FXI) have been investigated in randomized controlled trials as a new option with more favorable outcomes. A comprehensive literature search was conducted to identify relevant studies comparing FXI inhibitors to placebo or standard therapy. The primary outcomes were incidence of all bleeding events, major bleeding, and thromboembolism. Secondary outcomes included incidence of all adverse events (AE), serious AE, and all-cause mortality. A total of 11 studies involving 10,536 patients were included. FXI inhibitors were associated with a trend toward reduction of bleeding events and incidence of thromboembolism compared to the control group (placebo/standard therapy). There was no statistically significant difference between both groups in terms of adverse events and all-cause mortality. When compared to enoxaparin, FXI inhibitors significantly reduced the risk of bleeding events (RR = 0.42, 95% CI: 0.23–0.76, P = 0.004) and thromboembolism (RR = 0.59, 95% CI: 0.44–0.77, P = 0.001). On the other hand, when compared to DOACs, FXI inhibitors were associated with a significant reduction in bleeding events but not thromboembolism. Whereas, compared to placebo, FXI inhibitors did not increase the risk of bleeding events, adverse events, or all-cause mortality (P > 0.05). FXI inhibitors could be a safer and more potent option for prevention of thromboembolism than conventional therapy.

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Abbreviations

FXI:

Factor XI

AE:

Adverse events

SAE:

Serious adverse events

RR:

Risk ratio

TKA:

Total Knee arthroplasty

AF:

Atrial fibrillation

ESRD:

End-stage renal disease

VTE:

Venous thromboembolism

MI:

Myocardial infarction

DOACs:

Direct oral anticoagulants

VKAs:

Vitamin K antagonists

MR:

Mendelian randomization

RCTs:

Randomized clinical trials

LMWH:

Low molecular weight heparin

BMI:

Body mass index

APTT:

Activated partial thromboplastin time

DVT:

Deep vein thrombosis

PE:

Pulmonary embolism

TIA:

Transient ischemic attack

INR:

International normalized ratio

ISTH:

International Society on Thrombosis and Hemostasis

BARC:

Bleeding Academic Research Consortium

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Author information

Authors and Affiliations

  1. Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Ahmed E. Ali & Marwan H. Ahmed

  2. Department of Anesthesia and Critical Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Mohamed K. Awad

  3. Department of Medicine, Hennepin Healthcare, Minneapolis, MN, USA

    Karim Ali

  4. Department of Medicine, Baptist Hospitals of Southeast Texas, Beaumont, TX, USA

    Mohamed Riad Abouzid

  5. Department of Surgery, Mayo Clinic, Rochester, MN, USA

    Muhammad S. Mazroua

  6. Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Ahmed E. Ali, Karim Ali, Mohamed Riad Abouzid, Marwan H. Ahmed & Muhammad S. Mazroua

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  1. Ahmed E. Ali
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Ali, A.E., Awad, M.K., Ali, K. et al. Factor XI as a new target for prevention of thromboembolism in cardiovascular disease: a meta-analysis of randomized controlled trials. J Thromb Thrombolysis (2024). https://doi.org/10.1007/s11239-024-02986-z

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