Vytorin: No good reason to use, yet 80,000 prescriptions a week

The Medical Letter is an non-profit, non-industry funded publication that reviews therapeutics. They are one of the few unbiased sources about drugs, sort of like a Consumer Reports for pharmaceuticals. The Medical Letter is a paid subscription service, so you may not have access to their recent article on Ezitimibe Revisited. Ezitimibe or Zetia is the second compononent of Vytorin, which combines Zetia with a statin (simvastatin). The Medical Letter describes both the ENHANCE trial and the SEAS study, both studies which showed no benefit of Vytorin. I have blogged about Vytorin and these studies in previous posts (including Zetia In, Vytorin Out and Dear Doctor: Vytorin ), and the good folks at The Medical Letter have drawn the same conclusions I have.


"A large clinical-endpoint trial in patients with hypercholesterolemia comparing the simvastatin-ezetimibe combination with simvastatin alone is underway; results are expected in 2012. Until then, drug treatment of hypercholesterolemia should continue to aim at achieving LDL-C levels below 100 mg/dL in high-risk patients and, if possible, below 70 mg/dL for patients at very high risk. For patients who cannot achieve these goals with a safe dose of a statin alone, adding another LDL-C lowering drug such as niacin, a bile acid sequestrant or ezetimibe continues to be a reasonable option."

In other words, for patients requiring cholesterol lowering drugs, first start with a statin. If goals can not be achieved, several options including adding Zetia seem reasonable. Since other statins such as Lipitor or Crestor are more potents then simvastatin and other generics, if cholesterol goals can't be acheived with a generic, a switch to a more potent statin should be considered (or Lipitor or Crestor should be started in patients whose LDL is too high for simvastatin to acheive control). If cholesterol goals are still not acheived, then one can add Zetia. Thus, there is really no reason to ever use Vytorin. Interestingly, as of last month, according to the Wall Street Journal, "new prescriptions for Vytorin in the US have held steady at more than 80,000 a week over the last month."

Vitamin D, COPD and Kevin MD

I am back from break and desperately trying to catch up with patient messages, lab results, etc. as well as the latest medical news.

Reader take on Kevin MD
Thank to Kevin for posting my reading take As psychiatry goes, so will primary care on his blog. Medical blogs written by physicians tend to focus on either health care policy/politics, personal experiences or comments on medically relevant items. This blog focuses on the latter, but I recently sent this reader take to Kevin on the future of primary care.

Vitamin D
A new study published in the Annals of Internal Medicine showed that women with low vitamin D levels have a much greater risk of fracture than women with normal or high vitamin D levels.
According to the National Osteoporosis Foundation, "adults under age 50 need 400-800 IU of vitamin D daily, and adults age 50 and older need 800 – 1,000 IU of vitamin D daily." Though vitamin D supplementation has not been proven to prevent fractures, the strong association with fracture prevention, biologic role in bone formation and low risk of taking it seem to support these recommendations

Inhaled Steroids in COPD
Another study that came out while I was away was a post-hoc analysis of the TORCH study that showed that a combination of an inhaled steroid and long acting beta agonist (Advair) slowed the progression of lung function loss in patients with COPD. Chronic Obstructive Lung Disease (COPD) contributes to the 4th leading cause of death in the US. Normally, in people who don't smoke, the amount of air you can forcefully blow out in one second (FEV1) declines as we age. In patients who smoke and/or have COPD, that rate of loss of lung function is much more rapid, leading to substantial declines in the ability to function as well as premature death. Up until this study, the only thing that had been shown to slow this progression of lung function decline was to stop smoking. This is the first drug that is able to make that claim.

The Toward a Revolution in COPD Health (TORCH) study, was designed to show that Advair reduced mortality compared to placebo or the individual components alone in over 6000 patients taking one of these agents for over 3 years. Though Advair decreased mortality, it was not statistically significant. There was a significant reduction in exacerbations, though there were a few excess pneumonias as well. This analysis was done after the trial was completed and found that both the long acting beta agonist (salmeterol), the inhaled steroid (fluticasone) and the combination (Advair) all slowed the rate of decline in FEV1 compared to placebo, though reduction was greater with the combination.

Though nothing beats stopping smoking, this is good news for patients with COPD who may benefit from medications that address not only their symptoms but other factors, including loss of lung function.

Gone to the Beach!

I will be away this week.
In the meantime, keep up with what is going on in the medical blogsphere by checking out KevinMD.

Prostate Cancer Screening

As mentioned in the New York Times, the U.S. Preventive Services Task Force recently updated its prostate cancer screening guidelines, reaffirming that evidence is lacking to recommend for or against it, and took an additional new step stating that physicians should not routinely screen for prostate cancer in men over 75. This is in contrast to recommendations by other organizations such as the American Cancer Society that recommends doctors offer a PSA blood test and DRE (digital rectal exam) yearly, beginning at age 50 to men who can be expected to live at least 10 more years, and for men at high risk (African American, family history of prostate cancer) screening should begin at age 45.

Why the difference and what should you do?
On the one hand, in 2007, prostate cancer was the leading cause of new cancers for men and second only to lung cancer for cancer death in men. Organizations like the American Cancer Society who are determined to get rid of all cancer encourage screening. On the other hand, it is not clear that finding and then treating prostate cancer will save one's live. This is likely due to the fact that many prostate cancers are slow growing, and men will often die of something else before the prostate cancer spreads. In addition, treatment for prostate cancer is not without risks and complications, such as problems with urination and sexual function.

There is not right answer here, and it is important that you discuss all screening with your doctor. One key thing to determine is that screening and finding cancer doesn't necessarily mean more testing and treating. For example, you might have a PSA test done that is greater than normal, and determine that before proceeding to further testing (biopsy) you might watch and wait. For this reason, I still recommend screening, but advise caution when addressing a positive test. Based on your individual risks, values, etc. you and your physician can determine how best to proceed.

Vytorin: Using medical reports for media hype and political attention

If you are a reader of this blog, you will know that I am no fan of Vytorin. Despite their massive marketing campaign, Merk-Schering has failed to prove why treating the "two sources of cholesterol" has any benefit to just treating patients with a statin. Both the ENHANCE study and SEAS studies (the only outcomes studies thusfar) failed to show any benefit of Vytorin , and thus there is really no need to use it.

However, the Vytorin saga seems to have struck and chord with the public, and so folks are piling on.

It was not surprising that many of the media outlets like Forbes, MSNBC, ABC news and others reported on the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial. As I have mentioned in a previous post, SEAS compared Vytorin to placebo in about 1800 patients with aortic stenosis, and showed no difference in the primary endpoint of both aortic valve events combined ischemic events (nonfatal MI, coronary, CABG, etc.). It was also not surprising to see that the media reported on an unexpected finding in the study, double the risk of cancer for those patients taking Vytorin.

However, apparently congress is now asking for a cancer investigation. According to the Wall Street Journal:


In a letter to the FDA, Rep. John Dingell (D., Mich.) said that based on the study's finding, "Vytorin may not be safe. Its potential for cancer and cancer deaths may be a significant cause for concern among physicians and patients."


And of course, this brings more media attention to the issue. The problem is that this is a non-issue. The SEAS study was not a Merk-Schering study. Cancer rates in the SEAS study were doubled, (106 in the Vytroin group versus 67 in the controls) but absolute difference was about 7% and did not reach (though it came close) statistical significance. Moreover, there is really no biologically plausible reason for Vytorin to cause cancer . In addition, as a result of these findings, analysis of large ongoing Vytorin studies (IMPROVE-IT and SHARP) showed fever cancers in the Vytorin group (313) then in patients not taking Vytorin. In other words, Vytorin very likely does not cause cancer.

On the one hand, I am in favor of further reasons for physicians not to prescribe/patients not to take Vytorin. On the other hand, I am annoyed that congressmen are using media-hyped anti-pharma fear to try to earn political clout. I would be the first to say that further scientific investigation on the issue of Vytorin and cancer is probably warranted. However, let's leave this to the scientists and the FDA. Why does congress need to get involved? Aren't there better things for them to worry about, like say 47 million Americans without health insurance?