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Our patients are often taking warfarin. How does that affect the choice of a statin?

APOLLO User

Warfarin is metabolized through several cytochrome P450 (CYP450) pathways, any of which might serve as a basis for interactions with statins and potential increases in the international normalized ratio (INR). The CYP3A4-dependent statins such as simvastatin¹ and lovastatin² have the potential to raise the INR in patients taking warfarin. Since the effect is variable, the INR should be monitored before and after the statin is introduced, after dose titration, and periodically thereafter to determine whether the warfarin regimen requires adjustment. Atorvastatin, however, although it is CYP3A4-dependent, has failed to demonstrate any clinically significant effect on prothrombin time when administered to patients receiving long-term warfarin therapy.^3,4 In patients receiving maintenance therapy with warfarin who were administered atorvastatin (80mg/d) for 2weeks, the mean prothrombin time decreased slightly for only the first few days of treatment.⁴ Fluvastatin, metabolized through the CYP2C9 pathway, can also interfere with warfarin metabolism and raise the INR.⁵ Rosuvastatin, which is also metabolized through the CYP2C9 pathway, appears to raise the INR in patients taking warfarin, but without raising their warfarin concentrations. This suggests that the effect is not mediated through the CYP450 system but more likely is caused by a partial displacement of warfarin from its protein-bound state in the circulation.⁶ Pravastatin, which is not metabolized through any of the CYP450 pathways, did not have any clinically significant effect on prothrombin time in elderly patients receiving a stable dosage of warfarin.⁷

MacRae F. Linton, MD

References

1. Zocor [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2005.

2. Mevacor [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2005.

3. Stern R, Abel R, Gibson GL, Besserer J. Atorvastatin does not alter the anticoagulant activity of warfarin. J Clin Pharmacol. 1997;37:1062-1064.

4. Lipitor [package insert]. New York, NY: Pfizer Inc; 2005.

5. Andrus MR. Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature. Pharmacotherapy. 2004;24:285-290.

6. Barry M. Rosuvastatin-warfarin drug interaction. Lancet. 2004;363:328.

7. Pravachol [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2005.