Sandra A. Fryhofer, MD Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia; Past President, American College of Physicians, Philadelphia, Pennsylvania

Savvy Statin Shopping

Let's go shopping. This edition of Staying Well focuses on how to be a savvy shopper in choosing a statin for your patients, a timely issue in light of the US Food and Drug Administration's (FDA's) new simvastatin warnings. Seasoned shoppers always check the sale racks first, but don't buy something -- even if on sale -- if the "size and style" aren't right. Apply this analogy to picking a statin. Although the first thing to look for is price, it should not be the only deciding factor. Simvastatin is certainly one of the cheapest statins, but is it the best choice for your patients?

My Personal Disclaimer

I admit that I have been a little lazy. For the last several years, when my patients needed statins I always started with simvastatin. It was generic. It was on all the pharmacy plans, so the price point for patients was right. Prescribing was hassle free: no cumbersome forms to fill out and explain. However, the recent FDA warnings about the dangers of high-dose simvastatin and additional warnings about dosing and drug interactions have led me to rethink this strategy and take a closer look at the different statins available. It is now time to find out the facts and make necessary changes in prescribing patterns. Maybe it's time for a new "style" of treatment. Here is some information to help you decide.

Statin Characteristics

This statin dose equivalency guide gives equivalent doses of available statins along with generic and brand names and selected characteristics (Table 1).^[1-5]

Table 1. Statin Dose Equivalency Guide

Medication	Dose Equivalent	Pharmacotherapeutic Factor	Metabolism	Metabolites
Rosuvastatin (Crestor®)	2.5 mg	Hydrophilic	CYP2C9	Active (minor) metabolite
Atorvastatin (Lipitor®)	5 mg	Lipophilic	P450 3A4 (CYP3A4)	Active metabolite
Simvastatin (Zocor®)a	10 mg	Lipophilic	P450 3A4 (CYP3A4)	Active metabolite
Lovastatin (Altoprev®, Mevacor®)	20 mg	Lipophilic	P450 3A4 (CYP3A4)	Active metabolite
Pravastatin (Pravachol®)	20 mg	Hydrophilic	Renal metabolism	No active metabolites
Fluvastatin (Lescol®, Lescol® XL)	40 mg	Lipophilic	CYP2C9	No active metabolites
Pitavastatin (Livalo®)	1 mg	Lipophilic	Little metabolism by CYP3A4	No active metabolites

^aAlso in combination medications: ezetimibe/simvastatin (Vytorin®) and niacin extended release/simvastatin (Simcor®)

Table 2 is from the FDA Drug Safety Communication and gives relative low-density lipoprotein (LDL) efficacy for the different statins. Note that pitavastatin (Livalo®) is a newer statin and was FDA approved in 2009.

Table 2. Relative LDL-Lowering Efficacy of Statin and Statin-Based Therapies

Atorva	Fluva	Pitava	Lova	Prava	Rosuva	Vytorin®a	Simva	%↓ LDL-C
--	40 mg	1 mg	20 mg	20 mg	--	--	10 mg	30%
10 mg	80 mg	2 mg	40/80 mg	40 mg	--	--	20 mg	38%
20 mg	--	4 mg	80 mg	80 mg	5 mg	10/10 mg	40 mg	41%
40 mg	--		--	--	10 mg	10/20 mg	80 mg	47%
80 mg	--		--	--	20 mg	10/40 mg	--	55%
	--		--	--	40 mg	10/80 mg	--	63%

Atorva = atorvastatin; Fluva = fluvastatin; LDL-C = low-density lipoprotein cholesterol; Pitava = pitavastatin; Lova = lovastatin; Prava = pravastatin; Rosuva = rosuvastatin; Simva = simvastatin
^aNo incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.
Data from US Food and Drug Administration. June 8, 2011. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm ^[4]

Association of Pharmacologic Factors With Adverse Effects

Statins that are hydrophilic (pravastatin and rosuvastatin) are less likely to cross skeletal muscle membranes and are less likely to cause adverse effects.^[3]

Statins that don't have active metabolites (fluvastatin, pravastatin, and pitavastatin) are less likely to cause adverse effects. Rosuvastatin has only a minor active metabolite.^[3,5]

Drug metabolism pathway plays a role in drug-drug interactions and subsequent safety. This is especially important for patients on multiple medications:

• For statins metabolized by P450 3A4 (CYP3A4) (simvastatin, lovastatin, atorvastatin), concomitant administration of medications that inhibit the CYP3A4 pathways (protease inhibitors, cyclosporine, amiodarone, fibrates) is problematic. The result is increased statin levels and increased risk for muscle tissue injury.
• On the other hand, fluvastatin and rosuvastatin (metabolized by CYP2C9) and pravastatin (metabolized by the kidneys) are considered to be safer statin choices for patients on multiple medications.^[3]

Section 1 of 4

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