Two anti-platelet drugs studied for their effect on platelet function and immune activation post-procedure
Innovations in Cardiovascular Medicine & Surgery - Fall 2018
DAVID A. ZIDAR, MD, PHD
Co-Director, LDL Apheresis Program, University Hospitals Harrington Heart & Vascular Institute; Assistant Professor, Case Western Reserve University School of Medicine
Transcatheter aortic valve replacement (TAVR) has emerged as an important alternative to surgical aortic valve replacement. Still, the procedure can create systemic effects that must be managed for a good outcome.
“In the early days when our interventional cardiology and cardiac surgery group began to do these procedures, it was clear that many patients had some features of immune activation in the post-procedural period,” says David Zidar, MD, PhD, an interventional cardiologist with UH Harrington Heart & Vascular Institute. “Some patients develop a fever, other patients would have a lower blood pressure than we would expect. So we got interested in measuring some of the aspects of the immune system in this setting. We wanted to determine whether there might be pathways that we could alter to position patients for better recovery from the valve procedure.”
To find these pathways, Dr. Zidar and his team have begun to enroll TAVR patients in a prospective, randomized trial comparing two different anti-platelet medications – the standard therapy clopidogrel and the more potent ticagrelor.
“We proposed that by trying to optimize and understand the role of platelet activation before and after TAVR, we might also learn whether there are immunologic consequences to dampening platelet activation,” he says.
For the trial of 60 TAVR patients, Dr. Zidar and his team are measuring baseline markers of platelet function and immune activation. They’re then repeating the measurements after the anti-platelet drug is administered and the TAVR is performed – at one, seven and 30 days post-procedure.
The main goal of the trial, Dr. Zidar says, is to determine whether high-potency ticagrelor, compared with clopidogrel, affects platelet responsiveness and the pattern of monocyte activation seen early after TAVR. This trial will also begin to fill a knowledge gap of increasing importance -- which blood-thinning strategy is best for TAVR patients.
“In general, the medications that we give to patients undergoing TAVR have not been rigorously studied for the TAVR procedure itself,” Dr. Zidar says. “In our preliminary experience, we found that many patients who get the standard blood thinner, clopidogrel, don’t really respond to it very well. Their platelets don’t seem to be all that inhibited. There’s an alternative medicine, ticagrelor, which is more potent but also more consistent in its ability to dampen activation of platelets.”
“One line of investigation is how well these drugs inhibits platelets over a time course,” he adds. “Does the standard medicine catch up? Why are many of these patients resistant to clopidogrel? Another question is whether platelet activation promotes inflammation after this procedure, and if so, which immune pathways are downstream of platelets and which are independent. There is a lot of potential discovery about how the body responds to injury in general.”
Dr. Zidar says he expects that ticagrelor will be shown to be superior to clopidogrel in inhibiting platelets, but whether this translates to dampening immune activation is more uncertain.
“This trial will also allow us to begin to address larger future trials to determine whether ticagrelor leads to more bleeding and/or better long-term outcomes,” he says. “There are still many unanswered questions.