Fewer ischaemic events with higher clopidogrel dose and statin after carotid stenting

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In patients undergoing carotid artery stenting, a strategy using both a 600mg clopidogrel load and a short-term reload with high-dose atorvastatin protects against early ischaemic cerebral events, according to a study presented at the American College of Cardiology Scientific Session (9–11 March 2013, San Francisco, USA).

The ARMYDA-9 CAROTID trial, which was performed at two centres in Italy (Campus Bio-Medico University and European Hospital of Rome), sought to evaluate whether a strategy with a 600mg clopidogrel load and a short-term, high-dose atorvastatin reload would improve outcomes in clopidogrel-naïve, statin-treated patients undergoing carotid artery stenting.

“Optimal clopidogrel loading dose during carotid stenting has not been investigated; in addition, statin neuroprotection in this setting has not been described,” the investigators, led by Giuseppe Patti, Campus Bio-Medico University of Rome, Italy, wrote in the paper published simultaneously in the Journal of the American College of Cardiology.

A total of 156 consecutive clopidogrel-naïve patients were randomised using a 2×2 factorial design to receive either a 600mg (n=78) or 300mg (n=78) clopidogrel load given six hours before intervention and either a atorvastatin reload (n=76; 80mg + 40mg initiating 12 hours before the procedure) or no statin reload (n=80). The study included symptomatic and asymptomatic patients.

The primary endpoint was the 30-day cumulative incidence of transient ischaemic attack/stroke or new ischaemic lesions on cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) performed between 24 and 48 hours after stenting.

The results showed that the occurrence of the primary outcome measure was significantly lower in the 600mg clopidogrel arm (18% vs. 35.9% in the 300mg group, p=0.019) and in the atorvastatin reload arm (18.4% vs 35% in the no statin reload group, p=0.031). High-dose clopidogrel also significantly reduced the transient ischaemic attack/stroke rate at 30 days (0% vs 9%, p=0.02), a secondary endpoint, without increasing the risk of bleeding.

“Our findings showed that, in addition to mechanical cerebral protection, a strategy of more aggressive platelet inhibition with a higher clopidogrel loading dose may impart protection against thromboembolic procedure-related events, as reflected in an improved 30-day transient ischaemic attack/stroke incidence, independent of new cerebral lesions detected on DW-MRI,” the investigators wrote.

The authors added “These results, obtained along with routine mechanical neuroprotection, provide new evidence of the optimisation of drug therapy before percutaneous carotid intervention”.