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After Stent or Angioplasty: Effient (Prasugrel) Bests Plavix (Clopidogrel) for Patients with High Platelet Reactivity
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Plavix vs. Effient    

May 5, 2011 -- In the current issue of JACC Cardiovascular Interventions, a small study from Greece highlights an ongoing controversy over the optimal antiplatelet therapy for patients after angioplasty or stenting (a.k.a. percutaneous coronary intervention or PCI).

Antiplatelet therapy is necessary after stent placement to lower the risk of blood clotting inside the stent: an adverse event, known as stent thrombosis, that can trigger a heart attack.

The standard therapy has been aspirin plus clopidogrel (brand name Plavix) for 2-6 months after bare metal stents and a year or more after drug-eluting stents. But in July 2009, the FDA approved a new and more potent antiplatelet drug: prasugrel (brand name Effient). One caution about prasugrel has been that, because it is more powerful, it may have pose an increased risk of bleeding complications for the patient.

However, a number of recent studies have revealed that some patients are non-responders, or low-responders, to clopidogrel -- a drug that needs to be metabolized before it can be effective. A platelet reactivity test, often the VerifyNow assay from Accumetrics, is sometimes given where there are questions. High On-Treatment Platelet Reactivity (HTPR) may be a risk factor for stent thrombosis. Additionally, many of these low-or-no responders also have been shown to have a particular genetic marker, the CYP2C19*2 loss-of-function allele, determined through genetic testing. (For more information on these issues, read Angioplasty.Org's exclusive interview with Dr. Eric Topol.)

In this current study, the team headed by Dr. Dimitrios Alexopoulos, Department of Cardiology, Patras University Hospital, Patras, Greece, measured the platelet reactivity of 210 patients after PCI and found that one-third (71 patients) had high platelet reactivity, defined as a PRU of > 235. The patients were also genotyped to see if they had the CYP2C19*2 loss-of-function allele. The 71 patients were then randomized to a double-dose of clopidogrel (150mg) or the standard dose of prasugrel (10mg) and measured at 30 and then at 60 days.

The results of this small study were significant: all patients achieved an almost five-fold reduction in platelet reactivity across the board with prasugrel vs. clopidogrel (7.5% vs. 35.8%). Looking at only those patients with the 2C19*2 carrier, the reduction was even higher -- nine-fold (5.3% vs. 47.4%). This study, although small in number and therefore limited, bolsters the efficacy of individualizing antiplatelet therapy in patients who have high on-treatment platelet reactivity after stenting.

The authors conclude:

"For patients with HTPR after standard clopidogrel treatment after PCI, prasugrel 10 mg/day is more effective than clopidogrel 150 mg/day in reducing PR. This effect is more prominent in patients carrying 1 loss-of-function CYP2C19*2 allele. Hence, in HTPR patients, genotyping guidance might be helpful only in case an increased clopidogrel maintenance dose is considered. Measurement of platelet function in a post-PCI patient and subsequent treatment with prasugrel—if found with HTPR—seems to be the most effective strategy to overcome low responsiveness."


Reported by Burt Cohen, May 5, 2011