Findings from the meta-analysis may help guide patient counseling and remind clinicians to consider altering DAPT if needed.
Patients undergoing flow diversion for aneurysm repair who are hyper- or hyporesponders to standard dual antiplatelet therapy (DAPT) are more likely to experience hemorrhagic or thrombotic events, new data suggest. The study authors say they hope the data serve as a reminder to clinicians who evaluate platelet reactivity unit (PRU) levels to seriously consider altering their approach in patients who fall outside the therapeutic range.
“Increasingly, we are using devices to treat aneurysms that require dual antiplatelet therapy to prevent complications,” senior author Justin F. Fraser, MD (University of Kentucky, Lexington), told Neurovascular Exchange in a telephone interview. There also has been a growing interest in methods, the most common of which is VerifyNow (Accumetrics, San Diego, CA), to test responsiveness to the drugs and tailor care. Data on the actual risk of complications based on out-of-range PRU values are still lacking, however.
For their study, published online recently in Journal of NeuroInterventional Surgery, Fraser and colleagues, led by Ebunoluwa Ajadi, MD (University of Kentucky College of Medicine, Lexington, KY), surveyed the currently available literature from 2013 to 2018 to identify 12 studies comprising 1,464 patients who underwent Pipeline aneurysm repair and in whom the VerifyNow PRU assay was evaluated for its ability to predict thrombotic and hemorrhagic events. All included trials contained at least 30 cases during the study period.
Assay values were obtained prior to the procedures, and intraoperative and perioperative adverse events were noted. PRU value cutoffs ranging from > 200 to > 240 comprised the hyporesponders, and values ranging from < 60 to < 70 comprised the hyperresponders.
Among the 1,464 cases evaluated, 273 were men and the mean age was 58 years (range, 25-85 years). After loading with antiplatelet medications, preprocedural platelet hyperresponsiveness was associated with a greater incidence of hemorrhagic events, with an increased absolute risk of 12%. There was no observed relationship between hyperresponsiveness and thrombotic events.
On the other hand, preprocedural platelet hyporesponsiveness was associated with a greater incidence of thrombotic events, with an absolute risk of 15%. Hyperresponsiveness showed no relationship with hemorrhagic events.
Fraser acknowledged that the value of a meta-analysis such as this one is limited by the quality of the studies included. The tendency not to publish negative trials, he added, can bias the results.
An Important Reminder
Nevertheless, Fraser said he feels the meta-analysis adds value. “Our goal was to provide some hard numbers so that when a provider is speaking with a patient about what the risks are of flow diversion or another technology that uses dual antiplatelet therapy, they can at least provide some semblance of what is the true risk associated with being outside what is considered to be the accepted therapeutic range for antiplatelet activity,” he explained.
Fraser also hopes the study will remind clinicians to consider altering the therapeutic approach for patients who fall outside the therapeutic range. He noted a “huge variance” among institutions regarding how to manage such patients. At Fraser’s institution, for instance, they switch patients in subtherapeutic ranges to ticagrelor. For supratherapeutic patients, they stop DAPT for a week or two, initiate them on ticagrelor, and then proceed with the intervention.
“The important thing for us was to to provide these numbers so people who monitor the [PRU levels], but don’t change the treatment of the patient based on it, might think twice,” he said.
“In some ways neuroendovascular treatment of aneurysms has become more simplified over the years,” Fraser continued, “but it is a mistake to get lulled into a false sense of security. . . . We are entering an era in which we have to be more informed about how each person reacts to [aspirin and clopidogrel] because we are so much more dependent on them.”
Ajadi E, Kabir S, Cook A, et al. . J Intervent Surg. 2019;Epub ahead of print.
Fraser reports being an equity interest holder for Fawkes Biotechnology, and a consultant to Stream Biomedical, Penumbra, and Medtronic Neurovascular.