Cangrelor, a novel, intravenous P2Y12 platelet inhibitor, can safely be used as a long-term antiplatelet therapy for pediatric patients on continuous flow ventricular assist devices (VADs), according to research published in Artificial Organs by multiple Le Bonheur cardiologists and led by former Le Bonheur Pediatric Cardiology Fellow Sarah E. Fahnhorst, DO.
While previous studies have demonstrated viability of cangrelor in adult populations, this study was the first published on successful long-term use of cangrelor in pediatric patients. The study was co-authored by members of Le Bonheur’s VAD team, including Mohammed Absi, MD, Gary Beasley, MD, Umar Boston, MD, Jason Goldberg, MD, Hugo Martinez, MD, Kaitlin Ryan, MD, and Jeffrey A. Towbin, MD.
Former Le Bonheur Pediatric Cardiology Fellow Sarah E. Fahnhorst, DO (above left), led a study that showed the successful long-term use of cangrelor in pediatric patients on continuous flow ventricular assist devices (VADs). This therapy provides an alternative option for patients who don’t have an adequate response to common antiplatelet drugs.
“Thromboembolic events and bleeding are major sources of morbidity among pediatric patients supported on a VAD,” said Fahnhorst. “Cangrelor is short-acting, reversible and intravenous, making it a feasible antiplatelet agent in select pediatric patients.”
Pediatric patients who are unable to take or do not respond well to other antiplatelet drug options can safely remain on a VAD by using cangrelor. This allows for a lower risk of blood clotting or bleeding complications while they await heart transplant or recover from heart failure.
For optimal VAD function, pediatric VAD patients require a delicate balance between combating blood clot formation and preventing bleeding episodes. This dilemma has prompted development of new strategies to mitigate risks. The factors that affect this balance are numerous and include disruption of vascular endothelium, inflammatory response, renal function and impaired absorption and metabolism of antiplatelet drugs. In addition, 20-40% of the population are poor metabolizers of common antiplatelet drugs, such as clopidogrel and aspirin, and do not have an adequate response to these drugs. Therefore, an alternative option to long-term antiplatelet therapy is necessary for patients who need this crucial therapy.
The study followed seven patients at Le Bonheur Children’s who had end-stage heart failure and were supported on continuous flow VADs. The majority of patients were started on cangrelor because of impaired enteral absorption of oral P2Y12 antagonists or due to the inability to reach therapeutic goals. The median duration of a patient receiving intravenous cangrelor was 43 days.
Thromboembolic events and bleeding are major sources of morbidity among pediatric patients supported on a VAD. Cangrelor is short-acting, reversible and intravenous, making it a feasible antiplatelet agent in select pediatric patients.
Patients on cangrelor reached the therapeutic P2Y12 level in a mean of 1.86 days. No cerebrovascular events occurred while on cangrelor. There were two episodes of mild gastrointestinal bleeding, one episode of hematuria and one pump thrombosis. The number of these events are comparable or reduced when compared with previous statistics. Adequate platelet inhibition was achieved quickly and with a much lower dose of cangrelor than previously reported by the manufacturer.
“The quick onset of action and reversible nature of cangrelor is crucial when oral antiplatelet therapies cannot be implemented or bleeding is a concern,” said Fahnhorst.
Overall, this study showed that cangrelor is a successful, viable, long-term antiplatelet therapy in select pediatric VAD patients. Future studies would benefit from a larger sample size with a control group to further evaluate safety and effectiveness in the pediatric population.
“Cangrelor addresses some of the major pitfalls of oral antiplatelet therapy, including impaired enteral absorption, reversibility and epigenetic factors,” said Fahnhorst. “As more pediatric patients are placed on VAD support, cangrelor may be a feasible antiplatelet strategy.”
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