Statins Clopidogrel

Cardiovascular agents ACE inhibitors, clopidogrel, statins Altered intraglomerular hemodynamics, ihabdomyolysis... 

Serebruany VL, Midei MG, Malinin AI, Oshrine BR, Lowry DR, Sane DC, Tanguay JF, Steinhubl SR, Berger PB, O Connor CM, Hennekens CH. Absence of interaction between atorvastatin or other statins and clopidogrel results from the interaction study. Arch Intern Med 2004 164(18) 2051-7. 

Wienbergen H, Gift AK, Schiele R, et al. MITRA PLUS Study Group. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003 92 285-288. 

PCI was performed using standard techniques (6,30). All 100 patients received one or more identical close cell-stent design. The same stent design was used in order to avoid potential bias with stent selection in both groups. All patients received 325 mg/day of aspirin indefinitely and clopidogrel as a loading dose of 300 mg on the day of the procedure and 75 mg/day thereafter for one month. Statins were given to all patients indefinitely. 

Fig. 19.1. Cumulative proportions of patients referred to the Early Use of Existing Preventive Strategies for Stroke (EXPRESS) study clinic in phases 1 — and 2 (—) prescribed new medication, (a) Any statin drug (in patients not already on a statin) (b) clopidogrel (usually in addition to aspirin) ...

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... 

The treatment of patients with symptomatic intracranial atherosclerotic disease can be summarized into prevention of occurrence of intraluminal thrombosis, plaque stabilization, and control of risk factors for atherosclerosis. Anticoagulation (compared with aspirin) has not shown to be beneficial in patients with intracranial atherosclerotic disease [24]. Current guidelines recommend that aspirin alone, the combination of aspirin and extended release dipyridamole, and clopidogrel monotherapy (rather than oral anticoagulants) are aU acceptable options [24]. hi patients with hemodynamically sigifificant intracranial stenosis who have symptoms despite medical therapies (antithrombotics, statins, and other treatments for risk factors), the usefulness of endovascular therapy (angioplasty and/or stent placement) is uncertain and is considered investigational [22, 25],... 

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. 

Dose may be an important factor as to whether or not a significant clinical interaction occurs. One study found that a high loading dose of clopidogrel (600 mg) was not affected by statins, but there is increased risk of serious bleeding with this dose. Lower doses of statins (e.g. atorvastatin 10 mg daily) also appear to be less likely to interact, and one study found that the effect was dose-dependent. ... 

Serebruany VL, Mahnin AI, Calldian KP, Gurbel PA Steinhubl SR Statins do not affect platelet inhibition with clopidogrel during coronary stenting. A roscUrosis (2001) 159, 239-41. 

MachF, SenoufD, Fontana P, BoehlenF, Reber G, Daali Y, deMoerloose P, SigwartU.Not all statins interfere with clopidogrel durii antiplatelet therapy. Eur JCtin Invest(2005) 35, 476-81. 

Ford I, Williams D Does the use of statins compromise the effectiveness of platelet inhibiticn by clopidogrel Platelets (2004) 15,201-5. 

Neubauer H, Mugge A. Do statins really interfere with clopidogrel-induced platelet function Reply. Circulation (2003) 108,448-9. 

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. ... 

In the cases where rhabdomyolysis developed when clopidogrel was added to treatment with eielosporin and a statin it was thought that the addition of clopidogrel (which may also inhibit the cytochrome P450 enzyme system) may have destabilised the delicate metabolic equilibrium between the statins and eielosporin precipitating the development of rhabdomyolysis. 

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