A novel regimen of alternate day clopidogrel would provide a cost-effective strategy to prevent very late stent thrombosis

作者：Sharma Sanjiv^*; Forrester James S

来源：Medical Hypotheses, 2012, 78(1): 166-170.

DOI：10.1016/j.mehy.2011.10.018

Background/objectives: ACC/AHA/SCAI recommendations include dual anti-platelet therapy (aspirin and clopidogrel) for 12 months after drug-eluting stent percutaneous coronary intervention (DES PCI). Numerous case reports have emerged of "very late stent thrombosis" (VLST) (>1 year post-DES-PCI) even 1-5 years after DES-PCI manifesting with myocardial infarction and death when clopidogrel therapy was interrupted or stopped.
Hypothesis: We hypothesize that a novel regimen of alternate day clopidogrel would provide a cost-effective strategy to prevent VLST taking into account the known facts about clopidogrel pharmacodynamics, stent endothelialization and stent thrombosis.
We hypothesized that the degree of anti-platelet effect required to prevent VLST decreases with time as the stent endothelializes-that is the "therapeutic threshold" required to prevent VLST decreases with time. The anti-platelet effect of clopidogrel lasts for 5-7 days. Typically, stent thrombosis on interruption of clopidogrel (with bare metal stents within first 30 days) occurs after 3-4 days signifying recovery of enough platelet function to produce stent thrombosis - recovery of platelet inhibition beyond the therapeutic threshold. Since the therapeutic threshold required to prevent VLST in DES after 1 year is much lower, this degree of platelet inhibition can be conceivably achieved with just administering clopidogrel on alternate days.
Empirical data: We studied efficacy and safety of regimen of daily aspirin 81 mg and alternate-day clopidogrel 75 mg beyond 12 months after PCI with DES for prevention of VLST by following 347 patients for occurrence of death, myocardial infarction (MI), VLST, target vessel revascularization (TVR) and bleeding. There were no occurrence of major bleeding, VLST events or death.
Conclusions: Long term dual anti-platelet therapy with aspirin 81 mg daily and clopidogrel 75 mg every other day beyond 12 months after PCI with DES may be a safe and efficacious cost-saving strategy to prevent VLST.

• 出版日期2012-1