Study Emphasizes Tecarfarin's Promise and Need for Improved Anticoagulation in LVAD Patients

Cadrenal Therapeutics, Inc. has spotlighted a recent study that emphasizes the potential advantages of tecarfarin, a novel vitamin K antagonist (VKA), for patients with left ventricular assist devices (LVADs). Tecarfarin, which differs from the traditionally used warfarin, targets a distinct metabolic pathway, potentially offering more consistent and effective anticoagulation. This advancement is critical for LVAD patients, who often face significant complications, such as gastrointestinal bleeding, which leads to recurrent hospital admissions and high healthcare costs.

The peer-reviewed manuscript, published in the Journal of Cardiac Failure, explores the relationship between time in therapeutic range (TTR) and clinical outcomes in LVAD patients. Co-authored by Dr. Mandeep R. Mehra from Brigham and Women's Hospital Heart and Vascular Center, the study titled "Antithrombotic Strategies with Left Ventricular Devices," underscores the necessity of evolving anticoagulation therapies to mitigate gastrointestinal bleeding, a common issue that adversely affects patient quality of life and healthcare expenses.

Dr. Mehra, chair of the ARIES-HM3 study, notes that tecarfarin holds promise for LVAD patients requiring chronic anticoagulation. Unlike warfarin, tecarfarin is not influenced by drug-drug interactions or renal function changes, making it a potentially more stable option for these patients.

A secondary analysis of the ARIES-HM3 trial, sponsored by Abbott, highlighted a median TTR of 56% for VKA management. The findings revealed a 47% reduction in bleeding risk for patients with a TTR above the median, suggesting a significant inverse relationship between TTR and bleeding events. Patients with lower TTRs experienced more sub-therapeutic International Normalized Ratios (INRs) than supra-therapeutic INRs, with no clear link between higher INRs and bleeding incidents.

Quang X. Pham, Chairman and CEO of Cadrenal Therapeutics, expressed optimism about tecarfarin's potential, stating that these findings enhance confidence in tecarfarin's ability to address the critical unmet needs in anticoagulation for LVAD patients. Cadrenal Therapeutics is eager to collaborate with the LVAD community to advance this next-generation VKA.

Tecarfarin is the only oral anticoagulant under development globally for patients with implanted cardiac devices and rare cardiovascular conditions. By bypassing the cytochrome P450 system and instead utilizing carboxyl esterase for metabolism, tecarfarin avoids many drug interactions, potentially offering more stable anticoagulation, especially for patients with renal dysfunction—a common issue in LVAD patients.

In a Phase II study involving 66 patients with atrial fibrillation who were switched from warfarin to tecarfarin, the mean interpolated TTR reached 71.4% within three weeks, with minimal time spent in extreme INR ranges. If approved, tecarfarin could be the only on-label anticoagulant for LVAD patients in the U.S.

Additionally, tecarfarin may benefit patients who do not achieve recommended anticoagulation with warfarin due to genetic resistance or renal impairment. This group includes individuals with end-stage kidney disease and atrial fibrillation or those with mechanical heart valves and difficult-to-control INRs.

Cadrenal Therapeutics has announced discussions with Abbott regarding a pivotal study of tecarfarin in patients with newly implanted LVADs. The only LVAD currently available in the U.S. is Abbott's HeartMate 3TM. Moreover, the U.S. Food and Drug Administration (FDA) has granted tecarfarin Orphan Drug Designation for preventing thromboembolism and thrombosis in patients with mechanical circulatory support devices, including LVADs.

Cadrenal Therapeutics is committed to developing tecarfarin to meet unmet needs in anticoagulation therapy. With orphan drug and fast-track designations from the FDA, tecarfarin aims to prevent systemic thromboembolism in patients with end-stage kidney disease and atrial fibrillation. Tecarfarin leverages a different metabolic pathway than warfarin and has been evaluated in multiple clinical trials, demonstrating general tolerability in both healthy adults and patients with chronic kidney disease.