Patti G, Tomai F, Melfi R, et al.
J Am Coll Cardiol. 2013 Feb 8. doi: 10.1016/j.jacc.2013.01.015.

Background

Evidence exists that in the setting of coronary stenting the degree of platelet inhibition is inversely correlated with the incidence of myocardial ischemic events [1, 2]. It is unknown whether a higher dose (600 mg vs the currently used 300 mg) is also beneficial in clopidogrel-naive patients undergoing carotid stenting. Long-term statin therapy appears to decrease the incidence of periprocedural ischemic cerebral incidents around the time of carotid stenting [3], thus initiation of statin therapy before percutaneous carotid intervention is now recommended [4]. However, it is unknown whether a decrease in ischemic cerebral events may be obtained by a short-term reload with high-dose atorvastatin in patients undergoing carotid stenting. The ARMYDA-CARO (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting) study is a prospective, randomized trial which evaluates whether a 600-mg clopidogrel load (vs. the 300-mg dose) or atorvastatin reload (vs. no reload) given briefly before intervention improves early outcome in clopidogrel-naïve, statin-treated patients undergoing percutaneous protected carotid intervention with stent implantation.

Main results

• The 30-day cumulative incidence of TIA/stroke or new ischemic lesions as seen on cerebral CW-MRI was lower after 600 mg clopidogrel, as compared to patients receiving 300 mg (18% vs 35.9%, P=0.019), irrespective of history of stroke.
• No patient who received 600 mg clopidogrel had suffered from TIA or stroke at 30 days, whereas 9% of patients receiving the conventional dose did (P=0.02).
• Atorvastatin reload yielded a lower incidence at 1 month of TIA/stroke or new ischemic leasions as compared to patients who did not receive statins (18.4% vs 35%, P-0.031), irrespective of history of stroke.

Conclusion

Patients with carotid stenosis undergoing stent implantation who received a 600-mg loading dose of clopidogrel showed fewer early ischemic cerebral events than did patients receiving the conventional 300 mg dose. Similarly, a short-term reload with high-dose atorvastatin significantly prevents ischemic cerebral events, even after long-term statin therapy. Thus, a strategy involving a more aggressive platelet inhibition appears protective against thromboembolic procedure-related events in patients undergoing carotid stenting, without increasing bleeding risk.

References

1. Patti G, Nusca A, Mangiacapra F, Gatto L, D’Ambrosio A, Di Sciascio G. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol 2008;52: 1128–33.
2. Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study.
3. Gröschel K, Ernemann U, Schulz JB, Nägele T, Terborg C, Kastrup A. Statin therapy at carotid angioplasty and stent placement: effect on procedure-related stroke, myocardial infarction, and death. Radiology 2006;240:145–51.
4. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease. J Am Coll Cardiol 2011;57:1002–44.

Abstract

OBJECTIVES:
This study sought to evaluate whether a strategy with a 600-mg clopidogrel load and a short-term, high-dose atorvastatin reload would improve outcomes in clopidogrel-naïve, statin-treated patients undergoing protected carotid stenting.

BACKGROUND:
Optimal clopidogrel loading dose during carotid stenting has not been investigated; in addition, statin neuroprotection in this setting has not been described.

METHODS:
A total of 156 patients were randomized using a 2 × 2 factorial design to receive either a 600-mg (n = 78) or 300-mg (n = 78) clopidogrel load given 6 h before intervention and either a atorvastatin reload (n = 76; 80 mg + 40 mg initiating 12 h before the procedure) or no statin reload (n = 80). The primary endpoint was the 30-day incidence of transient ischemic attack/stroke or new ischemic lesions on cerebral diffusion-weighted magnetic resonance imaging performed at 24-48 h.

RESULTS:
Occurrence of the primary outcome measure was significantly lower in the 600-mg clopidogrel arm (18% vs. 35.9% in the 300-mg group; p = 0.019) and in the atorvastatin reload arm (18.4% vs. 35.0% in the no statin reload group; p = 0.031). High-dose clopidogrel also significantly reduced the transient ischemic attack/stroke rate at 30 days (0% vs. 9%, p = 0.02, secondary endpoint), without an increase in bleeding risk.

CONCLUSIONS:
In patients undergoing carotid stenting, a strategy using both a 600-mg clopidogrel load and a short-term reload with high-dose atorvastatin protects against early ischemic cerebral events. These results, obtained along with routine mechanical neuroprotection, provide new evidence of the optimization of drug therapy before percutaneous carotid intervention. (Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting [ARMYDA-CARO], NCT01572623).