Simvastatin warning

Recently my doctor informed me of the FDA warning about high doses of simvastatin. Since I’ve been taking the 80mg dose that the FDA suggests is not advisable any longer, I looked at some of the alternatives.  My brother claims that he controls his cholesterol quite effectively just with diet, but he keeps a very strict vegan diet that I would have difficulty adhering to, so I’m still looking at statin drugs.

The FDA conveniently gives the roughly equivalent dosages of statin drugs on the market:

Relative LDL-lowering Efficacy of Statin and Statin-based Therapies

Atorva	Fluva	Pitava	Lova	Prava	Rosuva	Vytorin*	Simva	%↓ LDL-C
—–	40 mg	1 mg	20 mg	20 mg	—–	—–	10 mg	30%
10 mg	80 mg	2 mg	40 or 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; Pitava=Pitavastatin; Lova=Lovastatin; Prava=Pravastatin; Rosuva=Rosuvastatin; Simva=Simvastatin.

Given that I needed 80mg of simvastatin to keep my LDL below 130, it looks like fluvastatin, pitavastatin, lovastatin, and pravastatin are not suitable.  (In the past I’ve taken lovastatin, pravastatin, and atorvastatin—the use of simvastatin was a combination of needing something stronger and avoiding the higher prices of brand-name drugs.)

Now it looks like my choices are narrowed to 40 mg atorvastatin (Liptor), 10 mg rosuvastatin (Crestor), and 10/20 mg ezetimibe/simvastatin (Vytorin).  All three are covered at the same level by my health insurance ($20/month co-payment).  One advantage to atorvastatin is that it goes off-patent soon, so generics will become available, which would lower my co-payment to $5/month.

Since all three are available in doses that have similar effect on LDL, I decided to look at the effect on HDL as well, since my total/HDL ratio is still a bit too high, even on 80 mg simvastatin.  Initially, the best comparison I could find was an infomercial by the makers of Crestor: Raising HDL Cholesterol: Comparative Data | CRESTOR® (rosuvastatin calcium).  It seems that increasing dosage of atorvastatin decreases HDL, rather than increasing it, so atorvastatin does not look like a good choice for me.  They do not show a comparison with Vytorin, though.

Given the choice between Crestor and Vytorin, it is harder to find data to compare their effects on HDL level at the dosages at which they provide the same effect on LDL. I finally found the FDA website on Vytorin, which is confusingly located on drugs.com rather than a government website.  It lists the dose response of Vytorin:

Table 7: Response to Vytorin in Patients with Primary Hyperlipidemia (Mean* % Change from Untreated Baseline†)

Treatment (Daily Dose)	N	Total-C	LDL-C	Apo B	HDL-C	TG*	Non-HDL-C
* For triglycerides, median % change from baseline † Baseline – on no lipid-lowering drug ‡ Vytorin doses pooled (10/10-10/80) significantly reduced total-C, LDL-C, Apo B, TG, and non-HDL-C compared to simvastatin and significantly increased HDL-C compared to placebo.
Pooled data (All Vytorin doses)‡	609	-38	-53	-42	+7	-24	-49
Pooled data (All simvastatin doses)‡	622	-28	-39	-32	+7	-21	-36
Ezetimibe 10 mg	149	-13	-19	-15	+5	-11	-18
Placebo	148	-1	-2	0	0	-2	-2
Vytorin by dose
10/10	152	-31	-45	-35	+8	-23	-41
10/20	156	-36	-52	-41	+10	-24	-47
10/40	147	-39	-55	-44	+6	-23	-51
10/80	154	-43	-60	-49	+6	-31	-56
Simvastatin by dose
10 mg	158	-23	-33	-26	+5	-17	-30
20 mg	150	-24	-34	-28	+7	-18	-32
40 mg	156	-29	-41	-33	+8	-21	-38
80 mg	158	-35	-49	-39	+7	-27	-45

Similarly, the official FDA page for Crestor gives dose response

Table 5. Dose-Response in Patients With Hyperlipidemia (Adjusted Mean % Change From Baseline at Week 6)

Dose	N	Total-C	LDL-C	Non-HDL-C	ApoB	TG	HDL-C
Placebo	13	-5	-7	-7	-3	-3	3
Crestor 5 mg	17	-33	-45	-44	-38	-35	13
Crestor 10 mg	17	-36	-52	-48	-42	-10	14
Crestor 20 mg	17	-40	-55	-51	-46	-23	8
Crestor 40 mg	18	-46	-63	-60	-54	-28	10

It looks like Crestor increases HDL more than Vytorin for the dose with comparable effect on LDL, so my doctor and I decided to try 10mg Crestor for the next few months.  The number of people in the Crestor table seems astonishingly low—I wonder if there is a better dose-response table somewhere (the official data from AstraZeneca does not seem to have anything more than this).

It is also difficult to estimate the risks of liver damage and muscle damage, though I’m not too worried about those, as I’ve been taking statins for 20 years and seen only modest increases in liver enzymes. I will, of course, continue to have blood tests for the liver enzymes once or twice a year (and within 3 months of any change of prescription).