A new study provides strong evidence for the need for platelet function testing before the procedure, researchers say.
For patients treated with the Pipeline device, a poor response to clopidogrel confers a substantially increased risk of thromboembolic events postprocedure, new data show. Adjusting the antiplatelet regimen to address hyporesponse dramatically reduces this risk.
The results, published in the May 2017 issue of Stroke, are among the first to provide compelling evidence that all patients undergoing placement of Pipeline (Medtronic) should have platelet function testing first, its investigators say.
“The Pipeline embolization device (PED) is becoming a mainstay treatment for intracranial aneurysms since its approval by the FDA in 2011,” senior author Ajith Thomas, MD (Beth Israel Deaconess Medical Center, Boston, MA), told Neurovascular Exchange in an email.
“Unique to the PED is a three- to fivefold increase in surface coverage area as compared to other stents designed for intracranial use,” he noted. “This large surface coverage can cause platelet activation and act as a nidus for thromboembolic complications. The risk of these complications varies widely based on factors like age of the patient, location of the aneurysm, length of procedure, and number of PEDs placed, with an overall rate of 4-9%.”
Dual antiplatelet therapy is used routinely to minimize this risk, Thomas explained, but there is growing evidence that up to half of the population is genetically hyporesponsive to clopidogrel and may therefore not reap the full benefits of this gold standard antiplatelet agent. While platelet function testing can identify these patients, it is still not routinely used by interventionalists, largely due to lack of evidence supporting its utility.
Thomas and colleagues conducted a retrospective review of prospectively maintained databases from three academic institutions for the years 2009 to 2016, identifying all 402 patients who underwent a combined total of 414 Pipeline procedures for the treatment of intracranial aneurysms.
Overall, thromboembolic complications occurred in 9.2% of procedures and produced symptoms in 5.6%.
Risk of thromboembolic events was higher among clopidogrel nonresponders than responders 17.4% vs 5.6%; P = 0.0002), as detected by three platelet function tests. Among nonresponders, switching to ticagrelor lowered the risk compared with remaining on clopidogrel (2.7% vs 24.4%; P = 0.004). Finally, among nonresponders who stayed on clopidogrel, the risk was lower if they received a clopidogrel boost within 24 hours preprocedure than if they did not (9.8% vs 51.9%; P = 0.00004).
There was no significant difference in the rate of hemorrhagic complications between groups.
Magnitude of Difference a Surprise
Thomas told NVX that while it was expected that patients with poor responses to clopidogrel would have a higher rate of thromboembolic complications, the magnitude of this difference and the large impact of changing the antiplatelet regimen were surprising.
“The findings of this study provide the first strong evidence on the importance of [platelet function testing] prior to PED placement,” he said. “A recent survey by our center showed that about 80% of interventionalists surveyed in the US do in fact use [platelet function testing], but only half of those would switch to an alternate antiplatelet regimen. The rate is even lower outside the US.”
According to Thomas, choosing a clopidogrel boost or a switch to ticagrelor in hyporesponsive patients depends largely on the preferences of the clinician and the center. While ticagrelor is more expensive, it has a much more rapid onset of action and can be stopped temporarily, if needed, to place an external ventricular drain, with a low risk of bleeding. He also pointed out that the lower rate of thromboembolic events with ticagrelor seen here “supports a trend towards using ticagrelor routinely in all patients prior to PED placement, regardless of the response status.”
Thomas acknowledged that the study is limited by its retrospective design and variability in the management of patients across centers. He noted, however, that the inclusion of several institutions in the analysis should increase the generalizability of the findings.
While he would like to see future randomized controlled trials compare ticagrelor with other alternative antiplatelet agents, Thomas pointed out that the findings of this study would make it ethically unacceptable to include a comparison group of poor responders receiving a standard clopidogrel dose.
Adeeb N, Griessenauer CJ, Foreman PM, et al. Use of platelet function testing before pipeline embolization device placement: A multicenter cohort study. Stroke. 2017;48:1322-1330.
Thomas reports no relevant conflicts of interest.