The Source for Neurovascular News and Education

August 11, 2020


The results highlight the importance of clopidogrel response testing prior to Pipeline implantation, researchers say.


Prasugrel is a safe and effective component of dual antiplatelet therapy for patients undergoing treatment of cerebral aneurysms using a Pipeline device and who are either clopidogrel hyporesponders or have contraindications for the drug, a study published recently in the Journal of Neurosurgery shows.

Additionally, researchers found that, in two patients who could not take prasugrel, ticagrelor proved safe and effective.

The findings now provide “a protocol for a second or third option” in clopidogrel hyporesponders, Pascal Jabbour, MD (Thomas Jefferson University Hospital, Philadelphia, PA), told Neurovascular Exchange, adding, “If patients are resistant to prasugrel, they can be started on ticagrelor.”

Jabbour and colleagues identified 437 consecutive patients (mean age 56.3 years; 14.2% women) who underwent treatment of cerebral aneurysms with Pipeline flow-diverting stents (Medtronic) in a tertiary referral center between January 2011 and May 2016. Of these, 22 were allergic to clopidogrel or had < 30% platelet inhibition in response to a daily 75 mg dose of clopidogrel and were therefore treated with prasugrel 10 mg daily (n = 20) or ticagrelor 90 mg twice daily (n= 2).

One of the seven patients lost to follow-up received prasugrel, and one patient was allergic to both clopidogrel and prasugrel. Patients were followed up for a mean of 15.8 ± 12.4 months.

Overall, 26 of 437 patients (5.9%) presented with a subarachnoid hemorrhage. All patients receiving prasugrel or ticagrelor had an mRS score ≤ 2 on their latest follow-up visit (mean score 0.67), and none died or suffered a long-term recurrence or a hemorrhagic event. Only one patient suffered from mild aphasia subsequent to a thromboembolic event.

Three patients taking clopidogrel died during the study, two from acute subarachnoid hemorrhage, and one from intraparenchymal hemorrhage. Clopidogrel, however, was not associated with increased mortality risk (OR 2.18; 95% CI 0.11-43.27).

Multivariate analysis showed that use of clopidogrel did not affect the mRS score on last follow-up (P = 0.14). Clopidogrel also was not associated with increased risks of long-term recurrence, thromboembolic complications, or hemorrhagic events.


Outcomes With vs Without Clopidogrel


Adjusted Odds Ratio (95% CI)

P Value

Long-term Recurrence

0.17 (0.01-2.70)


Thromboembolic Complication

0.46 (0.12-1.67)


Hemorrhagic Event

0.39 (0.91-1.64)



To NVX, Jabbour explained that approximately 20% of patients are resistant to clopidogrel, while at the same time an increasing number of aneurysms are being treated with stents and flow diverters that necessitate dual antiplatelet therapy.

Christoph J. Griessenauer, MD (Temple University, Philadelphia, PA; Geisinger Commonwealth School of Medicine, Scranton, PA), also speaking with NVX, estimated that the overall rate of inappropriate response to clopidogrel may be as high as 30% if one takes into account both under- and overresponders as well as those on medications that interact with the drug’s antiplatelet effects.

Both experts agreed that testing for clopidogrel response is crucial prior to all flow diverter interventions and that dual antiplatelet therapy must be adjusted to address responses outside the ideal range. Griessenauer pointed out that while clopidogrel response has not proven to be absolutely critical in the context of cardiac stenting, “there is growing evidence that the brain is different, and it’s absolutely critical to make sure patients respond to Plavix” prior to flow diverter use. In fact, he argued, it’s likely necessary prior to implanting any intravascular device in the brain.

Some disadvantages of changing to prasugrel, Jabbour acknowledged, are that it is more expensive than clopidogrel and contraindicated in patients with prior stroke.

But switching medications is not the only option. The standard protocol at Griessauer’s institution is to adjust the clopidogrel dose based on repeated testing of antiplatelet response. “We find using this approach that essentially all patients can become clopidogrel responders,” he explained. “But it requires judicious [testing and dose adjustment], which is cumbersome, so do I understand why some people choose to go to another drug.”

Jabbour recommended that his findings be confirmed in a prospective, randomized trial.





Atallah E, Saad H, Bekelis K, et al. The use of alternatives to clopidogrel in flow-diversion treatment with the Pipeline embolization device. J Neurosurg. 2017;Epub ahead of print.



  • Jabbour reports being a consultant for Medtronic.
  • Griessenauer reports no relevant conflicts of interest.