Low-Dose Prasugrel in Patients with Resistance to Clopidogrel for the Treatment of Cerebral Aneurysms

Abstract

Thromboembolism is one of the major complications of stent assisted coiling in treatment of cerebral aneurysm. Clopidogrel resistance is so common and prasugrel is more effective in its rapid and potent effect. We investigated changes in the value of P2Y12 resistance unit (PRU) when prasugrel was administered to patients with clopidogrel resistance. One hundred mg of aspirin and 75 mg of clopidogrel were administered for 5 days before the procedure, and PRU were examined. The resistance to clopidogrel was defined as the inhibition of PRU was less than 20%. PRU was re-examined after loading 20 mg of prasugrel. We treated 98 consecutive patients between January 2018 and July 2018, and 24 patients (24.5%) had resistance to clopidogrel. Nineteen patients were female. The mean PRU value at admission was 238.5±36.9 and the percentage inhibition value was 4.8±6.3%. After the use of prasugrel, the mean PRU and percentage inhibition values were measured as 124.9±49.9 and 48.0±19.24, respectively. All patients except one patient had a PRU inhibition value as a responder. There was no hemorrhage or thromboembolic complication during mean 1.5 months follow-up after embolization procedure. In conclusion, in patients resistant to clopidogrel, the low dose prasugrel seems to be effective in keeping the percentage inhibition value of PRU within the normal range in treatment of cerebral aneurysm. Further study will be needed to determine the optimal dose of prasugrel to enhance prevention effect of thromboembolism and to reduce hemorrhagic complications during stent assisted coiling.

The Usefulness of Prasugrel as Rescue Medication in Neuroendovascular Therapy

“…5) Internationally, several studies stated that low-dose prasugrel (loading dose: 20 mg, maintenance dose: 5 mg) was useful for the treatment of cerebral aneurysms. 7,20) A meta-analysis of these studies also demonstrated that low-dose prasugrel reduced thrombosis, and that it did not increase the incidence of hemorrhagic complications. 21,22) Furthermore, it was reported that the blood concentration of prasugrel reached a peak 30 minutes after administration; the interval until its effects were observed was shorter than that for clopidogrel (1 hour).…”

Comparison of Prasugrel and Clopidogrel Used as Antiplatelet Medication for Endovascular Treatment of Unruptured Intracranial Aneurysms: A Meta-Analysis

“…Similar results were achieved by other authors reporting low-dose PS with 20 and 5 mg used as loading and maintenance doses, respectively. 9,13,14 To our knowledge, our meta-analysis is the largest study comparing the outcomes of low-dose and high-dose PS versus standard-dose CP. First, the leave-one-out sensitivity metaanalysis (it was performed by iteratively removing 1 study at a time) showed that the exclusion of the series of Akbari et al 7 resulted in a significant reduction in the overall complication rate with the use of PS (OR ϭ 0.51; 95% CI, 0.26 -0.99; P ϭ .047) with low heterogeneity among studies (I 2 ϭ 32.5%).…”

“…Five studies compared treatment-related outcomes between the PS and the CP groups, [7][8][9][10]14 whereas 2 studies reported series of patients exclusively treated with PS. 12,13…”

“…Six studies were retrospective series, 7,8,10,12,13 whereas 1 study presented a prospective design. 9 Overall, 5 articles were rated as "high-quality" studies.…”

“…In 4 studies, 8,13,14 the loading dose of PS was 20 mg 1 day before treatment; in one study 9 it was 30 mg 1 day before treatment; in 2 studies, 10,12 the loading dose was between 40 and 60 mg 1 day before treatment; and in 1 study, 7 60 mg of PS was associated with 325 mg of acetylsalicylic acid (ASA). In 3 studies, CP, 75 mg, was combined with ASA, 100 mg 7,9 or ASA, 325 mg 10 , 5 days before treatment, whereas CP, 300 mg, was used alone in 2 studies 8,14 5 days before the procedure.…”