Results of the ARMYDA-9 CAROTID trial indicate that loading with 600 mg clopidogrel and high-dose atorvastatin in carotid stent patients independently result in improved neurological outcomes.
Results from the Efficacy of Two Different Pre-Intervention Therapeutic Strategies with Clopidogrel and Atorvastatin for the Prevention of Cerebral Damage During Carotid Artery Stenting. (ARMYDA-9 CAROTID) trial presented at ACC.13 showed clopidogrel loads of 600 mg “significantly reduced myocardial infarction versus the conventional dose [300 mg]” in patients undergoing PCI, said Giuseppe Patti, MD, Campus Bio-Medico University, and European Hospital, Rome, Italy.
Periprocedural loading with high-dose statin has also been beneficial in PCI patients. This blinded factorial trial examined the efficacy of 600 mg clopidogrel and high-dose statin in neuroprotection in carotid stent patients.
Chronic statin therapy (and clopidogrel-naive) patients undergoing carotid stenting were randomized to loading with 300 mg versus 600 mg of clopidogrel, and to atorvastatin reloading (80 mg 12 hours before intervention; 40 mg more than two hours before) versus no reloading. Procedures were performed using a standard femoral approach recommending mandatory use of cerebral protection.
Concurrent medications included beta-blockers (45%), periprocedural long-term aspirin therapy (100 mg/day), and intravenous 5000 IU of unfractionated heparin. Post-procedure, patients received daily doses of atorvastatin 40 mg, aspirin 100 mg (indefinitely), and clopidogrel 75 mg (for a month).
Finally, 156 patients were randomized, 78 each to clopidogrel 600 mg versus 300 mg; and 76 to atorvastatin reload, and 80 to no reload. Both groups shared similar baseline characteristics: 52% with diabetes mellitus, 24% peripheral arterial disease, 43% prior PCI, and 12% prior coronary artery bypass grafting. The majority (86%) had asymptomatic carotid stenosis. At baseline about 60% were on atorvastatin therapy. Median stenosis severity was 80%, and 14% of the patients had a thrombotic plaque. A distal embolic protection device was utilized in 98% of the patients. Median stent diameter was 7.5 mm.
A significant reduction in both new TIA/stroke (0% vs. 9%, P = 0.02) and new ischemic lesions was observed in the 600 mg clopidogrel group versus the 300 mg group (18% vs. 35.9%, P = 0.019) on cerebral diffusion-weighted MRI (18.0% vs. 33.3%, P = 0.044). A 30-day decrease in cumulative incidence of transient ischemic attack (TIA)/stroke or new ischemic lesions was seen on MRI with the higher-dosage group. Thirty-day incidence of death/MI/stroke was also lower in the 600 mg clopidogrel group (0% vs. 6.4%, P = 0.07). The incidence of vascular/bleeding complications was similar (6.4% vs. 10.3%, P = 0.56).
Due to a reduction in new ischemic lesions on MRI (17.1% vs. 33.8%, P = 0.028), 30-day cumulative incidence of TIA/stroke or new ischemic lesions on cerebral DW-MRI was also significantly lower in the loading group of high-dose atorvastatin than in the no-loading group (18.4% vs. 35.0%, P = 0.031). Thirty-day incidence of TIA/stroke was similar (1.3% vs. 7.5%, P = 0.14), as was incidence of vascular/bleeding complications (7.9% vs. 8.8%, P = 0.92).
Primary endpoints included 30-day cumulative incidence of TIA/stroke or new ischemic lesions at cerebral DW-MRI 24-48 hours post-procedure. Secondary endpoints included individual components of the composite primary endpoint; new lesions and those of >5 mm at DW-MRI; TIA/stroke at 30 days; and vascular/bleeding complications, including major or minor bleeding or entry-site complications (hematoma >10 cm, pseudoaneurysm or arteriovenous fistula).
The lowest incidence of the primary endpoint was in periprocedural patients receiving both 600 mg clopidogrel and high-dose atorvastatin, and highest in those receiving 300 mg clopidogrel and no loading dose of atorvastatin (18.9% vs. 53.9%, P = 0.004).
The results of the ARMYDA-9 CAROTID trial indicate that loading with 600 mg clopidogrel and high-dose atorvastatin in carotid stent patients independently result in improved neurological outcomes. Incorporating both medications appears to reduce ischemic cerebral events and TIA/stroke rates at 30 days, resulting in the fewest adverse outcomes.