Key result
High-dose apixaban (15 mg twice daily) prevented mechanical valve thrombosis in 3 of 3 pigs, whereas lower doses resulted in manifest or partial thrombosis in 4 of 6 pigs.
Why the study?
New mechanical valves have low thrombogenicity, but clinical trials of direct oral anticoagulants to replace warfarin have been disappointing so far.
Does apixaban prevent valve thrombosis in a porcine model of mechanical valve thrombosis?
Does apixaban prevent valve thrombosis in a porcine model of mechanical valve thrombosis?
High-dose apixaban shows potential to prevent mechanical valve thrombosis in a highly thrombogenic porcine model, though pharmacokinetic challenges remain.
Apixaban prevented thrombosis dose-dependently in this aggressive pig model without bleeding; leaves open optimal dosing and human translation.
OBJECTIVES: The newest mechanical valves have low thrombogenicity, making them candidates for anticoagulation with a direct oral anticoagulant. While these drugs hold great promise to replace warfarin, clinical trials have been disappointing so far. We aimed to evaluate apixaban in a porcine model of mechanical valve thrombosis with On-X® (CryoLife) aortic valves implanted in pulmonary position. METHODS: On-X® valves were implanted in pulmonary valve position in 9 Yucatan pigs. Animals received prophylactic enoxaparin 40 mg for 1 week. Pigs in the low-dose group received 5 mg apixaban twice daily for 10 weeks. The intermediary-dose group received 5 mg twice daily for 6 weeks and then 10 mg twice daily afterwards. The high-dose group received 15 mg twice daily for 10 weeks. After sacrifice, valves were macroscopically evaluated and thrombus weight was documented. RESULTS: The median weight of the 9 animals was 64.3 kg, range 52.5-70.9. In the low-dose group (2 animals), both valves showed manifest, chronic thrombosis with blocked hinges. In the intermediary-dose group, a normal functioning valve without thrombosis was seen in 2/4 animals. In the high-dose group (3 pigs), there was no valve thrombosis. No bleeding events occurred. In all animals, apixaban plasma levels were low compared to clinical target levels. CONCLUSIONS: The pulmonary position seems to be an aggressive model for mechanical valve thrombosis in pigs. Apixaban has the potential to prevent valve thrombosis, even in these thrombogenic conditions. Detailed pharmacokinetic studies are needed to determine the ideal apixaban dosage for future experiments and to enable extrapolation to the clinical situation.
No takes yet. Share an insight, caveat, or question.
Hoof et al. (2022) studied Mechanical valve thrombosis (n=9). Apixaban was evaluated on Valve thrombosis (macroscopic evaluation and thrombus weight). High-dose apixaban (15 mg twice daily) prevented mechanical valve thrombosis in 3 of 3 pigs, whereas lower doses resulted in manifest or partial thrombosis in 4 of 6 pigs.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: