Tuesday, July 22, 2008

On Statins and Cancer

The recently-released Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, a placebo-controlled study that examined the reduction in mortality and morbidity of patients with aortic stenosis taking ezetimibe (ZETIA) and simvastatin 40 mg, came with an unexpected finding: a higher-than-expected rate of cancer in the treatment arm compared to the placebo arm of the trial. Almost immediately, the business community stated:
The cancer finding was subjected to a series of analyses by a prominent research team at Oxford University in the United Kingdom. The researchers declared the finding "implausible" and probably the result of chance.


The data were given to a separate research group from Oxford University's Clinical Trial Service program. Sir Richard Peto, co-director of the program, analyzed the findings over the weekend. He reported during the London news conference that several factors, including the fact that patients had several different types of cancers and that there wasn't any increased incidence over time, convinced him that any real link between Vytorin and cancer was highly unlikely.
While their analysis might be true, when we look at the potential for this "implausibility," it is useful to recall that another statin generated the same "implausible" cancer findings: pravastatin.

In the PROSPER trial, new cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). Also, the CARE trial demonstrated a larger incidence of breast cancer diagnosis in the treatment group as compared to the placebo group. Other statins (specifically simvastatin and lovastatin), interestingly, have not been found to induce cancers. Some researchers have suggested this is because of the lipophylic (fat soluble) nature of those statins, compared the the hydrophyllic (water soluble) nature of pravastatin. Given the results of other studies, simvastatin might not be the culprit.

So what about ezetimibe? Or could the combination of the two drugs simvastatin and ezetimibe have an unexpected synergistic cancer-promoting effect? We really don't know. Certainly, the incidence and diversity of cancers indentified makes causation unlikely, but there are other studies that suggest that perhaps this relationship should be investigated further. For instance, in rodents, lowering of serum cholesterol by the unabsorbed bile acid–binding resin cholestyramine has been shown to promote mammary gland carcinogenesis.

So while I'm willing to accept the premise that the relationship of carcinogenesis is unknown with the simvastatin/ezetimibe combination, given the prior art of research available, I'm not sure I'm willing to write off the potential for a relationship as "implausible."


1 comment:

Anonymous said...

Yes, it has amazed me for years that the 'pushing' of these drugs has completely shadowed the known, and absolute impact of reducing simple carbohydrates in the diet on lowering total cholesterol, and bringing into balance (whether high OR low, it doesn't matter) the LDL HDL ratio. (Which is more to the point anyway).

Sigh... I guess you don't get brownie points for convincing a custo.. I mean patient to reduce their intake of simple sugars and thus reduce their 'cholesterol' levels.

The relationship between diabetic's high blood sugar and correlated lousy HDL LDL ratio is well known, but rarely addressed.

I'd suspect that is because drug companies have little to gain by this knowledge becoming 'common'. It is always surprising to me when I talk to diabetics in my pharmacy, that they don't understand this rather simple and elegant idea. They still want their 'statins' "'Cuz everybody KNOWS they work!"

Heck, I get paid more when I sell more of that junk too. But having read the studies (and having an undergraduate degrees in biochemistry AND statistics) that 'prove' statins are 'real great stuff', I remain unconvinced that there is much efficacy (if any). Even if there IS short term efficacy, the unknowns with these drugs is the proverbial elephant in the living room.

Big City Pharmacist