March 14, 2013

A 600-mg clopidogrel loading dose reduced periprocedural ischemic cerebral events and rates of transient ischemic attack (TIA) and stroke at 30 days in patients undergoing carotid stenting in the ARMYDA-9 CAROTID (Efficacy of Two Different Pre-Intervention Therapeutic Strategies with Clopidogrel and Atorvastatin for the Prevention of Cerebral Damage During Carotid Artery Stenting) study.

The study, presented at the American College of Cardiology meeting in San Francisco, California, earlier this week, also found that a short-term reload with high-dose atorvastatin significantly decreased cerebral events even though patients were already taking long-term statin therapy.

Reporting the data, Giuseppe Patti, MD, Campus Bio-Medico University, Rome, Italy, stated, "Drug therapy recommended in the guidelines for carotid stenting procedures is mainly derived from interventional coronary studies, whereas the ARMYDA-9 CAROTID study supplies evidence directly obtained in the specific setting of carotid intervention and may contribute to guide pharmacological management of carotid stenting."

The ARMYDA-9 CAROTID study, which was also published in the Journal of the American College of Cardiology on March 9, involved 156 clopidogrel-naive patients receiving long-term statin therapy who underwent carotid stenting.

The patients were randomly assigned to receive the following in a 2 x 2 factorial design: (1) clopidogrel, 600 mg, vs 300-mg loading dose and (2) atorvastatin reload with 80 mg 12 hours before intervention and a further 40-mg dose 2 hours before vs no statin reload.

The primary endpoint — the 30-day incidence of transient ischemic attack (TIA)/stroke or new cerebral lesions — was significantly reduced in the 600-mg clopidogrel loading-dose group.

Table 1. ARMYDA-9 CAROTID: Clopidogrel Results

Outcome 600-mg Clopidogrel Load (%) 300-mg Clopidogrel Load (%) P Value
TIA/stroke or new cerebral lesions 18.0 35.9 .019
Post-stenting new cerebral lesions 18.0 33.3 .044
Contralateral new cerebral lesions 6.4 11.5 .78
TIA/stroke - 9.0 .02
Vascular/bleeding complications 6.4 10.3 .56


The primary endpoint was also reduced with the atorvastatin reload:

Table 2. ARMYDA-9 CAROTID: Atorvastatin Results

Outcome Atorvastatin Reload (%) No Atorvastatin Reload (%) P Value
TIA/stroke or new cerebral lesions 18.4 35.0 .031
Post-stenting new cerebral lesions 17.1 33.8 .028
Contralateral new cerebral lesions 5.3 12.5 .19
TIA/stroke 1.3 7.5 .14
Vascular/bleeding complications 7.9 8.8 .92


Table 3. Primary Endpoint According to Clopidogrel/Statin Randomization

Endpoint Clopidogrel, 600 mg, Plus Atorvastatin Reload (%) Clopidogrel, 600 mg, No Atorvastatin Reload (%) Clopidogrel, 300 mg, Plus Atorvastatin Reload (%) Clopidogrel, 300 mg, Plus No Atorvastatin Reload (%)
30-day incidence of TIA/stroke or new cerebral lesions 18.9 17.1 18.0 53.9


Dr. Patti suggested that the faster and more intense platelet suppression at the time of intervention provided by high-dose clopidogrel load may prevent distal embolization, protect the microvascular bed, and counterbalance the postprocedural procoagulant status.

In addition, rapid, low-density lipoprotein–independent neuroprotective effects may be responsible for this atorvastatin benefit by limiting periprocedural microembolization and procedural injury, he added.

J Am Coll Cardiol. Published online March 9, 2013. Abstract

American College of Cardiology (ACC) 2013 Scientific Sessions. Presented March 9, 2013.