The safety and efficacy of factor XIa inhibitors for the prevention of stroke and thromboembolism: A systematic review and meta-analysis of randomized controlled trials

Review

作者: Noushad, Muhammad Ameen ; Iqbal, Fatima ; Jafar, Uzair ; Lal, Nauman ; Hussain, Waqar ; Farhan, Muzammil ; Ahmed, Mansoor ; Abdullah, Saad ; Nadeem, Anushah ; Ishaq, Amna ; Ahmed, Raheel ; Ayyan, Muhammad ; Zahid, Nayab ; Siddique, Amber ; Yousaf, Humyoun

BACKGROUND:

Stroke and thromboembolism remain the leading causes of mortality worldwide. Factor Xia inhibitors (FXIa) might prevent thromboembolism without interfering with hemostasis, thus leading to a lower risk of bleeding than direct oral anticoagulants (DOACs).

METHODS:

We conducted a systematic search using PubMed, Embase, and Clinicaltrials.gov to retrieve randomized controlled trials comparing FXIa inhibitors to placebo or DOACs in patients at risk of stroke or thromboembolism. All statistical analyses were carried out using RevMan 5.4, using a random effects model.

RESULTS:

Our meta-analysis included 14 RCTs involving 30,952 patients. FXIa inhibitors significantly decreased the risk of major bleeding (RR 0.47, 95% CI: 0.33-0.66, I²= 46%) with no significant change in systemic embolism or thromboembolism (RR 0.83, 95% CI: 0.64-1.07, I²= 70%). There was no significant change between the two groups when assessing the rate of all bleeding events (RR 0.78, 95% CI: 0.55-1.11, I²= 73%), all-cause mortality (RR 0.87, 95% CI: 0.70-1.09, I²= 0%), ischemic stroke (RR 0.99, 95%CI: 0.49-1.98, I²= 86%), myocardial infarction (RR 1.30; 95% CI, 0.54 - 3.13; I² = 68%), and intracranial hemorrhage (RR 0.49, 95% CI: 0.23- 1.05, I²= 9%). The rate of all adverse events (RR 1.05, 95% CI: 0.86-1.29, I²= 79%) and serious adverse events (RR 1.16, 95% CI: 0.86-1.55, I²= 74%) remained comparable between the two groups.

CONCLUSION:

In conclusion, FXIa inhibitors show promise as safer anticoagulant agents, demonstrating favorable bleeding outcomes without changing thromboembolism, mortality, or other safety outcomes. The presence of heterogeneity across various subgroups warrants data from further high-quality, large-scale RCTs to establish evidence of its clinical benefit. This is especially important in atrial fibrillation, where conflicting evidence regarding thromboembolism warrants cautious interpretation and further investigation.

2025-07-01·Cardiology in review

Factor XI/XIa Inhibitors: A New Approach to Anticoagulation

Review

作者: Whiteson, Harris Z. ; Frishman, William H.

For more than 60 years, anticoagulation drugs have served as a mainstay in preserving and improving the cardiovascular health of patients across the globe. Functioning to reduce a patient’s ability to produce blood clots, prescription rates for anticoagulants have been steadily rising year-over-year both in the United States and abroad. Despite decades of clinical usage, modern-day anticoagulants have been shown to predispose an individual to pathological bleeding. Even in seemingly benign instances of bleeding, patients on anticoagulation therapy might require intensive and expensive medical procedures or monitoring. Understanding the clinical implications of pathological bleeding, research and development of future anticoagulants seeking to minimize these effects. One emerging category of anticoagulant drugs are Factor XI/XIa (FXI) inhibitors. Targeting the coagulation cascade, clinical trials of Factor XIa inhibitors have shown promising results in preventing blood clot formation without increasing the instances of spontaneous and/or pathological bleeding events. While still in phase II and III clinical trials, and potentially years away from being implemented as standard of care, these novel drugs might have the potential to improve the safety and quality of life of patients taking anticoagulants. In this review, we discuss a brief history of anticoagulation therapy, followed by an analysis of the potential risks, benefits, and implications of Factor XI/XIa inhibitors across elements of patient care.

2025-07-01·Neurohospitalist

Factor XIa Inhibitor Reversal in Intracranial Hemorrhage: A Case Report

Article

作者: Strohm, Tamara ; Key, Nigel ; Smalley, Sierra ; John, Kayla ; Jones, Lee Ann ; Al-Obeidi, Arshed ; Garavito, Draia

Background/Objectives:

There is currently no consensus regarding the optimal strategy for reversal of anticoagulation in life-threatening hemorrhage associated with factor XIa (FXIa) inhibitors.

Methods:

For this clinical case report, informed consent was obtained from surrogate.

Results and Discussion:

Here, we present the case of an 82-year-old female who sustained a large subdural hematoma after a fall. Her aPTT on admission was elevated at 90.4 s and remained persistently prolonged at 90.9 s 12-hour after receiving an adequate dose of 4-factor prothrombin complex concentrate (PCC). She was found to have received a factor XIa inhibitor in a clinical trial, and subsequently received recombinant activated factor VII (rFVIIa) 2 mg (45 mcg/kg) as a one-time dose, and tranexamic acid (TXA) 1 g intravenously for reversal given her intracranial bleeding in the setting of trauma complicated by recent factor XIa inhibitor use. However, given her clinical decline and high surgical risk, the patient’s family elected to withdraw care and she expired three days later. Reversal of FXIa inhibitors is challenging but may best be achieved using a combination of rFVIIa and TXA.

Practical Implications:

Clinicians should consider administration of low dose recombinant activated factor VII (rFVIIa) in conjunction with an anti-fibrinolytic inhibitor such as tranexamic acid (TXA) for reversal of life-threatening hemorrhage in bleeding patients with exposure to novel factor XIa inhibitors that are currently in clinical trials.

项与 Factor XIa inhibitors(Novartis) 相关的新闻（医药）

2025-11-24

·BioPharmaDive

Bayer’s experimental blood-thinner notches trial win in stroke prevention

Dive Brief:Bayers experimental blood thinner asundexianmet its main goal in a closely watched Phase 3 stroke prevention trial, reducing the recurrence of a stroke in people who took the therapy along with standard treatments. The trial compared treatment with a combination of asundexian and an antiplatelet therapy against a placebo and the same antiplatelet treatment.The German-based company didnt release detailed data, stating that researchers will disclose them at an upcoming medical meeting while company executives discuss them with regulators ahead of possible approval applications.Results of the trial lifted optimism for asundexian'sdrug class, called Factor XIa inhibitors, following a series of clinical setbacks. Most recently, a rival drug missed its main goal in a trial of people whod had a recent heart attack.Dive Insight:The spotlight has been on Factor XIa inhibitors as the next big innovation in cardiovascular medicine, with drugmakers and researchers hoping they will prove safer and more effective than aging franchises like Bristol Myers Squibbs Eliquis. These drugs, which include asundexian,Bristol Myers and Johnson & Johnsons milvexian and Novartis abelacimab, block a protein involved in forming blood clots but is believed to be less essential in stopping bleeding.The balancing act in preventing stroke or any acute cardiovascular episode due to blood vessel blockages is in suppressing clotting without raising the risk that people will have uncontrolled bleeding incidents. In people who have irregular heartbeats, Eliquis is able to do just that better than an older drug called warfarin or aspirin.In treating people whove already had one stroke that wasnt caused by an irregular heartbeat, in a setting called secondary prevention, doctors use one or two drugs to thin the blood, known as antiplatelet medications. The drugs used include aspirin, clopidogrel, AstraZenecas Brilinta and Eli Lillys Effient.In the trial called Oceanic Stroke, Bayer aimed to measure whether adding asundexianto the mix would help, testing it against a placebo in over 12,000 people. The company said the experimental drug reduced the risk of ischemic stroke compared to placebo and added that its addition didnt increase the risk of major bleeding episodes.Bayers German-listed shares rose more than 12% following the news, changing hands at about 31 euros apiece. Two years ago, Bayer terminated a head-to-head trial of asundexianagainst Eliquis in people with irregular heartbeats, an early Phase 3 readout that cast some doubt over the promise of Factor XIa inhibitors.Milvexiansfailure in acute coronary syndrome earlier this month didnt boost optimism, but the asundexianresults may reverse some of the doubt.After a string of class setbacks, this is a needed win, wrote Cantor Fitzgerald analyst Carter Gould, who covers Bristol Myers, in a note to clients.Bristol Myers and J&J are expecting milvexiansPhase 3 trials in people with irregular heartbeats, as well as secondary stroke prevention, in the fourth quarter of 2026. Bristol Myers shares rose 5% in morning trading. '

临床3期

100 项与 Factor XIa inhibitors(Novartis) 相关的药物交易

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