Could Statins Be Protective Against H1N1 Flu?

In a retrospective study, it's a definite maybe:

Of the patients studied, 801 were taking statins anyway and continued taking them while hospitalized. Seventeen patients who were taking statins died while in the hospital or within a month afterward, compared to 64 who were not taking statins, Vandermeer said.

Overall, 2.1 percent of patients taking statins died, compared to 3.2 percent of patients not taking statins. That means patients taking statins were just under 50 percent less likely to die.

Turns out this is from a press release regarding reports being presented this weekend at the annual meeting of the Infectious Diseases Society of America (IDSA) in Philadelphia, so while the data are intriguing, they are by no means conclusive.

-Wes

Beware of the Simvastatin/Amiodarone Drug Interaction

For electrophysiologists, the drug combinations of amiodarone (marketed as Cordarone® or Pacerone®) and simvastatin (marketed as Zocor®) is a common drug combination. The FDA issued an alert that these two drugs, when taken together, might result in an increased incidence of rhabdomyolysis (injury to muscle cells characterized by muscle aches, weakness and dark urine). It is thought by some that this might result from competition of the two drugs for the same metabolic pathway in the liver:

Statins such as atorvastatin (Lipitor®), lovastatin (Mevacor®) and simvastatin (Zocor®)are metabolised via a cytochrome P450 3A-dependent pathway while fluvastatin (Lescol®), pravastatin (Pravachol®)and rosuvastatin (Crestor®) are metabolised via cytochrome P450 3A-independent pathways. As simvastatin and amiodarone are metabolised by the same isoenzyme, in the present case, the concomitant use of these drugs may have resulted in competition, resulting in excess of free plasma statin and thereby causing myotoxicity. However, there are limited publications on this interaction and the exact mechanism has not been established.

It is recommended to keep the daily simvastatin dose to 20 mg or less to avoid this side effect of the drug combination.

-Wes

h/t: WSJ.

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."

-Wes

Vytorin's Out, Simvastatin's In

Merck got handed its fanny today as Vytorin demonstrated no benefit over generic simvastatin in reducing plague in the carotid arteries. Merck knew the repercussions of this trial - and this likely was the reason its reporting was delayed: profit.

Stupid, really. Drug companies, in dire straights to rectify their relationship with the public, sided with their short-term monetary gains rather than improve their long-term public perception of the industry.

And they got burned.

Appropriately.

So now, we are left to wonder, what was that gain compared to generic simvastatin?

Turning to our handy-dandy CostCo cost analyzer, we find that a 30-day supply of Vytorin 10/20 (one of the lower-dose sizes), cost a whopping $97.17. Compare that to generic simvastatin 20 mg, at $5.82 - nearly 17 times the cost.

But that's not all. Let's not forget the cost for your time to call your doctor and change the prescription.

Or the costs involved at going to the doctor's office in person and getting a new prescription written. Costs that both you and your doctor have to absorb. Costs that cut dearly into your precious 7-minute primary-care visit.

And this cost is not inconsequential, especially when we realize that there were "1 million prescriptions written for it weekly."

-Wes

Havin' a Ball With Cholesterol

There's lots of news today on lipid-lowering drugs:

First, Merck is asking the FDA for the third time to permit lovastatin (Mevacor), the first HMG-CoA reductase inhibitor (or "statin"), to be sold over the counter. It seems twice is not enough. It's like telling a child "no" but they keep coming back, "Really, Daddy?" No! "Pretty please, daddy?" Not only no, but hell no!

So Merck is saying "pretty please?" and feels patients can understand a package insert like the one they use in Spain that says:

"Due to the inclusion of butylhydroxyanisol as excipient this may produce irritation of eyes, skin and mucous membranes."

Do they really think Americans will read this stuff? Ask yourself, do men read assembly instructions for a new kitchen appliance or ask for directions when lost? Of course not! Why would we read some stupid package insert from an over-the-counter medication? Does anyone read an acetaminophen (Tylenol) package insert? "Marge, just give me those damn pills!"

But seriously, the drug interactions with lovastatin alone are significant. Lovastatin is metabolized in the liver, and interacts with anticoagulants and antiarrhythmic drugs like Amiodarone, and can cause some rip-roaring myositis (inflammation of the muscles) in patients who might be taking other cholesterol-lowering medications like niacin or fibrates.

And heck, with simvastatin (formerly Zocor) available for $4 for 30 pills at Walmart by prescription and is likely cheaper, do Americans really need this?

Worse still, doctors have enough problems tracking prescribed medications on their patients. Will we really know what medications a patient is taking when all of these other medications want to be circulated over the counter?

Speaking of Zocor...

What's up with Merck and Schering-Plough withholding their results of the ENHANCE trial that compares, head to head, the combination drug Vytorin (simvastatin + ezetimibe) to simvastatin or placebo? This morning the WSJ Health Blog reports that the US House of Representatives Energy and Commerce Committee and Subcommittee on Oversight and Investigations is concerned "with the delay in releasing the results of the study, the timing of the ENHANCE trial registration (on ClinicalTrials.gov), and the apparent manipulation of trial data." (Letter here).

Since when has our Congress cared so much about scientific endeavors such as this? I mean, this is one of tons of other cholesterol trials out there. Are they really interested in the delay or could there be another political motive? Could it be because Michigan Democrat Bart Stupak was left off Schering-Plough's political donation list when Rep. John Dingell got $5000 or because Merck left Michigan off its contribution list entirely in 2006? Is Congress now suddenly interested if drug companies might be massaging their data just to get the results they want? Or have the Democratic House members been raising these questions because they just shorted Merck and Schering-Plough's stock?

I guess we'll have to wait for the March ACC meeting to find out.

-Wes

Addendum 13 Dec 2007 19:50 CST: Three strikes, they're out. The FDA rejects Merck's bid.

Pfizer: Coming Clean on Lipitor

Seems Pfizer admitted to the SEC that its superiority data regarding Lipitor (atorvastatin) over Zocor (simvastatin) was overstated. They might have the same efficacy rate. It seems they were forced to reconsider their claims:

The error was discovered while researchers were re-analyzing the data at the request of an expert who was reviewing the manuscript, which had been submitted for publication in a journal. (Pfizer senior vice president Michael) Berelowitz declined to name the publication.

Hmmm. I'm intrigued. There must me something going on here. Why would Pfizer suddenly decide to come clean and surrender their profits to generic simvastatin? Could people be on to their techniques?

-Wes

Reference: Wall Street Journal's Health Blog

Simvastatin Costs Vary Widely

Click chart to enlarge
This chart appeared in the Wall Street Journal this AM and discloses the remarkable variation in price on some generic drugs between pharmaceutical outlets. I was particularly struck by the cost variations of generic simvastatin (Zocor) between pharmacies.

But this quote was of particular interest:

Chain drugstores argue that their business model is different from a company like Costco or Sam's Club. CVS, Rite Aid and Walgreen Co. all say that about two-thirds of their revenues come from prescription drugs.

"We don't sell snow tires," says Mike DeAngelis, a spokesman for CVS/pharmacy. "The core of our business is the pharmacy."

Now that the word has gotten out and people run to Costco and Sam's Club, CVS might want to rethink the snow tire angle.

-Wes

P.S.: Another helpful site for drug price comparisons: Destinationrx.com.