Simvastatin Clopidogrel

Gorchakova O, von Beckerath N, Gawaz M, et al. Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting. Eur Heart J 2004 25 1898-1902. 

The FASTER randomized controlled pilot trial studied the benefit of clopidogrel versus placebo and simvastatin versus placebo initiated within 24-hours of symptom onset in patients with TIA or minor stroke, all of whom were treated with aspirin (Kennedy et al. 2007). The primary outcome was any stroke (ischemic and hemorrhagic) within 90 days. Minor stroke was defined as a score < 3 on the National Institutes of Health Stroke Scale (NIHSS) at the time of randomization and TIA was defined in the usual way. In addition, patients were excluded if they did not have weakness or speech disturbance or if symptom duration was less than five minutes. 

The study concluded that the combination of aspirin and clopidogrel started within 24-hours of symptom onset may be superior to aspirin alone in reducing the risk of stroke at 90 days after TIA or minor stroke, although at the expense of a higher rate of hemorrhage. These results form the basis of the FASTER-2 study, which will determine the risks and benefits of aspirin and clopidogrel compared with aspirin alone in larger numbers of patients. The FASTER trial did not show any benefit for simvastatin in the acute phase after TIA or minor stroke and no statin comparison is included in FASTER-2. 

STATINS ANTIPLATELET AGENTS -CLOPIDOGREL Atorvastatin and possibly simvastatin 1 the antiplatelet effect of dopidogrel in a dose-dependent manner Atorvastatin and simvastatin inhibit CYP3A4-mediated activation of dopidogrel Use these statins at the lowest possible dose otherwise consider using an alternative statin... 

Some evidence suggests that atorvastatin, and possibly other CYP3A4-metabolised statins (e.g. simvastatin) may interfere with the antiplatelet actions of clopidogrel, but the data is conflicting and there is currently insufficient evidence to warrant changing practice. 

There are at least 5 documented cases of rhabdomyolysis, one of which was fatal, " in patients given eielosporin and simvastatin. Another report describes a case of rhabdomyolysis when clopidogrel was added to treatment with eielosporin and simvastatin. In a review of the FDA spontaneous reports of statin-associated rhabdomyolysis covering the period November 1997 to March 2000, eielosporin was potentially implicated in 31 cases of rhabdomyolysis involving simvastatin. ... 

Malmstrom RE, Ostergren J, Jorgensen L, Hjemdahl P. Influence of statin treatment on platelet inhibition by clopidogrel—a randomized comparison of rosuvastatin, ator-vastatin and simvastatin co-treatment. J Intern Med 2009 266 457-66. 

---