Back in February, I posted about Lipitor and memory loss. This was in response to a piece on ABC news that one of my patients had reported to me. What I said at the time was essentially that there really wasn't any clear evidence that Lipitor causes memory loss, that even if it did it was an extremely rare side effect, and the benefit of Lipitor for patients at risk for heart attack and stroke clearly outweighed the risk of side effects, including the more common ones such as muscle pain (about 3-5%).
A new report has just come out showing that statin medications may in fact PREVENT memory loss. The five year study, published in today's issue of Neurology , followed 1,674 Mexican Americans 60 years or older who were initially free of any cognitive impairment. About 25% of these patients took statins at some point during the 5 years, as determined by actually looking in their medicine cabinets. Patients mental function was tested every year or so. During the 5 year study, 130 subjects developed dementia or cognitive impairment. This risk was decreased by half for those patients who had taken a statin.
Bottom Line: This study is not a randomized trial, thus one should not start taking a statin medication for the sole purpose of preventing dementia or memory loss. However, these results are reassuring in that, if anything, statins like Lipitor probably prevent memory loss, not cause it.
Tuesday, July 29, 2008
Thursday, July 24, 2008
Viagra for Women, No to Breast Exams and More Bad News for Vytorin
Sorry I have not posted for a while. With the start of a new school year (the medical school academic calendar goes from July to July) I have been kneed deep in multiple projects. Here are a few short takes on some recent items in the news.
Viagra for Women
The Wall Street Journal and others have recently reported about using Viagra in women. This comes from a study in JAMA that found that in women who had experienced sexual dysfunction after taking an antidepressant like Prozac or Celexa, the 49 women who took Viagra compared to the 49 women who took placebo had an improvement in sexual function.
There are a few caveats here. In addition to being a relatively small study, the outcome measure was a sexual function score based on a doctor rated scale between 1 (normal) and 7 (most extreme sexual dysfunction). Though the difference between the groups was statistically significant, the difference was less than a point on this scale. More importantly, the women studied here were very specific: depressed women who had no problems with sexual functioning until they had started an anti-depressant. Maybe instead of taking a second pill, they should have switched to another anti-depressant that doesn't cause sexual dysfunction, like bupropion.
Bottom Line: Sexual dysfunction in women is a MAJOR problem that doesn't seem to have a lot of funded research, and thus no real proven treatment options. If Viagra really worked for women, you would know about it, as I am sure countless women have tried this on their own. Male erectile function is both a nerve and blood flow problem, and Viagra (a vasodilator) clearly works on this second component. Female sexual dysfunction is much more complicated, and likely due to multiple factors, of which blood flow is probably only a minor component. More research is needed on this important problem, including studies on Viagra, but for now, I would not recommend Viagra for women.
No More Breast Exams
Several sources, including MSNBC recommend "Ladies, give your breasts a rest." This is based on a recently released review of the literature that showed that after studying thousands of women, not only was there no improvement in picking up breast cancer, but because of increased numbers of likely unnecessary biopsies, doing self breast exams may have also actually have caused harm.
Bottom Line: Breast cancer is one of the leading cause of cancer, and leading cause of cancer deaths in women. Early detection and treatment can save lives. On the other hand, not all screening is best for every patient. In addition, there is a risk to any screening, even if it is something as seemingly harmless as examining your own breasts, because if you find something, that you will need a test, which often (biopsy) has side effects. This study shows that making general recommendations for everyone may not be a great idea. For example, the incidence of breast cancer in women under 35 is about the same as the risk for breast cancer in men, and you don't see men examining their breasts! Though others suggest young women do self-breast exams to "get in the habit early", based on this study this practice is not warranted. On the other hand, patients at high risk may benefit from self-breast exams, such as women above 50, especially with a family history. In other words, some ladies can (and should) "take a rest", but not necessarily everyone.
More Bad News for Vytorin.
As reported in several sources, including Forbes, the most recent study on Vytorin was not exactly positive. The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial compared Vytorin to placebo in about 1800 paients with aortic stenosis, a stiffening of one of the heart valves. The primary endpoint was a combination of aortic valve events (valve-replacement surgery, heart failure, and cardiovascular mortality) and ischemic events (nonfatal MI, coronary, CABG, need for catheterization, unstable angina, and cardiovascular death). The study found no difference in the primary outcome, but did find a small difference in the secondary ischemic outcome. However, there was also a non-significant increase in cancer diagnosis in the Vytorin group.
Bottom line: On the one hand, the cancer increase is probably nothing to worry about, since this wasn't statistically significant and has not been seen in other trials. On the other hand, you can't make too much of a secondary endpoint (ischemic events) when Vytorin is compared to placebo. Lowering ldl cholesterol does matter. The issue is whether or not Vytorin is worth the extra cost (of generic simvistatin) or whether, when necessary, it is better to use a more potent statin like Lipitor or Crestor. With ENHANCE and SEAS, studies with Vytorin have failed to show why treating two sources of cholesterol is better then treating one (despite the drug company's huge advertising campaign suggesting this is important). Though I will add Zetia when I can't get to goal with another statin, I see no role for Vytorin anymore.
Viagra for Women
The Wall Street Journal and others have recently reported about using Viagra in women. This comes from a study in JAMA that found that in women who had experienced sexual dysfunction after taking an antidepressant like Prozac or Celexa, the 49 women who took Viagra compared to the 49 women who took placebo had an improvement in sexual function.
There are a few caveats here. In addition to being a relatively small study, the outcome measure was a sexual function score based on a doctor rated scale between 1 (normal) and 7 (most extreme sexual dysfunction). Though the difference between the groups was statistically significant, the difference was less than a point on this scale. More importantly, the women studied here were very specific: depressed women who had no problems with sexual functioning until they had started an anti-depressant. Maybe instead of taking a second pill, they should have switched to another anti-depressant that doesn't cause sexual dysfunction, like bupropion.
Bottom Line: Sexual dysfunction in women is a MAJOR problem that doesn't seem to have a lot of funded research, and thus no real proven treatment options. If Viagra really worked for women, you would know about it, as I am sure countless women have tried this on their own. Male erectile function is both a nerve and blood flow problem, and Viagra (a vasodilator) clearly works on this second component. Female sexual dysfunction is much more complicated, and likely due to multiple factors, of which blood flow is probably only a minor component. More research is needed on this important problem, including studies on Viagra, but for now, I would not recommend Viagra for women.
No More Breast Exams
Several sources, including MSNBC recommend "Ladies, give your breasts a rest." This is based on a recently released review of the literature that showed that after studying thousands of women, not only was there no improvement in picking up breast cancer, but because of increased numbers of likely unnecessary biopsies, doing self breast exams may have also actually have caused harm.
Bottom Line: Breast cancer is one of the leading cause of cancer, and leading cause of cancer deaths in women. Early detection and treatment can save lives. On the other hand, not all screening is best for every patient. In addition, there is a risk to any screening, even if it is something as seemingly harmless as examining your own breasts, because if you find something, that you will need a test, which often (biopsy) has side effects. This study shows that making general recommendations for everyone may not be a great idea. For example, the incidence of breast cancer in women under 35 is about the same as the risk for breast cancer in men, and you don't see men examining their breasts! Though others suggest young women do self-breast exams to "get in the habit early", based on this study this practice is not warranted. On the other hand, patients at high risk may benefit from self-breast exams, such as women above 50, especially with a family history. In other words, some ladies can (and should) "take a rest", but not necessarily everyone.
More Bad News for Vytorin.
As reported in several sources, including Forbes, the most recent study on Vytorin was not exactly positive. The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial compared Vytorin to placebo in about 1800 paients with aortic stenosis, a stiffening of one of the heart valves. The primary endpoint was a combination of aortic valve events (valve-replacement surgery, heart failure, and cardiovascular mortality) and ischemic events (nonfatal MI, coronary, CABG, need for catheterization, unstable angina, and cardiovascular death). The study found no difference in the primary outcome, but did find a small difference in the secondary ischemic outcome. However, there was also a non-significant increase in cancer diagnosis in the Vytorin group.
Bottom line: On the one hand, the cancer increase is probably nothing to worry about, since this wasn't statistically significant and has not been seen in other trials. On the other hand, you can't make too much of a secondary endpoint (ischemic events) when Vytorin is compared to placebo. Lowering ldl cholesterol does matter. The issue is whether or not Vytorin is worth the extra cost (of generic simvistatin) or whether, when necessary, it is better to use a more potent statin like Lipitor or Crestor. With ENHANCE and SEAS, studies with Vytorin have failed to show why treating two sources of cholesterol is better then treating one (despite the drug company's huge advertising campaign suggesting this is important). Though I will add Zetia when I can't get to goal with another statin, I see no role for Vytorin anymore.
Tuesday, July 8, 2008
Tendon rupture with Cipro? FDA caves to Public Citizen
Once again, in an attempt to show strength in its ability to protect the public, the FDA shows its weakness by caving to Public Citizen (a group that clearly hates the pharmaceutical industry) by placing a boxed warning on fluroquinolone antibiotics like Cipro and Levaquin.
What's the concern?
According to the FDA:
"Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture. This risk is further increased in those over age 60, in kidney, heart, and lung transplant recipients, and with use of concomitant steroid therapy."
Tendinitis and tendon rupture are usually associated with sports injuries with younger people. The mechanism by which these antibiotics cause tendon problems remains a mystery.
How serious is this?
On the one hand, these problems are not life threatening. However, they can cause severe pain and disability. As far as warnings go; however, a boxed warning is a pretty serious warning. I have posted previously on the FDA's different levels of warnings. (Note: There is no such thing as a "Black Box", it is a boxed warning. The "black" is something scary the media added). Tendon rupture had been mentioned in these antibiotic's label as an adverse event, so by adding the boxed warning, the FDA is stating this is a greater concern.
So if the problem is serious, why is the warning a bad thing?
According to the Washington Post, The FDA's action came after the consumer group Public Citizen petitioned and later sued the agency for such warnings. Public Citizen's review of the adverse events from November 1997 through Dec. 31, 2005 showed 262 reported cases of tendon ruptures, 258 cases of tendinitis, and 274 cases of other tendon disorders. This is a ridiculously low number if one considers the millions and millions of prescriptions that have been written for quinolone antibiotics such as Cipro. The FDA stated it had recently done its own "new" analysis, which is why it added the boxed warning. However, they do not present the details of their findings. To me, this implies that they simply caved from public pressure and/or from law suit threats. This is a problem, because so many patients who have or will have taken these medications will be needlessly worried. Even worse, some patients might simply stop taking their antibiotics. Finally, further hype regarding drug dangers continues to create an unnecessary fear about medications among the public. This is evident with publications like the "8 drugs doctors would never take" which I previously blogged about, later showing that when you asked real doctors, they completely disagreed (I will follow up on this post shortly).
In my opinion, the FDA showed similar weakness in response to the Avandia hype. As I have blogged previously, based on data they had at the time, and even more recent data, the risk of heart attacks and Avandia just doesn't seem to be true. Yet, the FDA changed its label, scaring and confusing patients and physicians. (The recent recommendations about approval of future diabetes drugs are similar actions).
Bottom Line
One thing that shouldn't be overlooked is that despite my opinion that the boxed warning is likely unnecessary and unhelpful, quinolone antibiotics are over-prescribed. A once powerful drug, many bacteria are now resistant to Cipro because of over-use. Newer generations of fluroquinolones are likely similarly over-prescribes (as are antibiotics in general). That said, there are some conditions mild (uncomplicated urinary tract infections) and more serious (pneumonia) where therapy is appropriate. In those cases, these medications should be used. The boxed warning should be taken into consideration (consider alternatives for elderly and immunosuppressed patients and/or warn appropriately), but for the general public, tendinitis and tendon rupture was so rare, even by Public Citizen's numbers, that this should still be considered a rare adverse event.
What's the concern?
According to the FDA:
"Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture. This risk is further increased in those over age 60, in kidney, heart, and lung transplant recipients, and with use of concomitant steroid therapy."
Tendinitis and tendon rupture are usually associated with sports injuries with younger people. The mechanism by which these antibiotics cause tendon problems remains a mystery.
How serious is this?
On the one hand, these problems are not life threatening. However, they can cause severe pain and disability. As far as warnings go; however, a boxed warning is a pretty serious warning. I have posted previously on the FDA's different levels of warnings. (Note: There is no such thing as a "Black Box", it is a boxed warning. The "black" is something scary the media added). Tendon rupture had been mentioned in these antibiotic's label as an adverse event, so by adding the boxed warning, the FDA is stating this is a greater concern.
So if the problem is serious, why is the warning a bad thing?
According to the Washington Post, The FDA's action came after the consumer group Public Citizen petitioned and later sued the agency for such warnings. Public Citizen's review of the adverse events from November 1997 through Dec. 31, 2005 showed 262 reported cases of tendon ruptures, 258 cases of tendinitis, and 274 cases of other tendon disorders. This is a ridiculously low number if one considers the millions and millions of prescriptions that have been written for quinolone antibiotics such as Cipro. The FDA stated it had recently done its own "new" analysis, which is why it added the boxed warning. However, they do not present the details of their findings. To me, this implies that they simply caved from public pressure and/or from law suit threats. This is a problem, because so many patients who have or will have taken these medications will be needlessly worried. Even worse, some patients might simply stop taking their antibiotics. Finally, further hype regarding drug dangers continues to create an unnecessary fear about medications among the public. This is evident with publications like the "8 drugs doctors would never take" which I previously blogged about, later showing that when you asked real doctors, they completely disagreed (I will follow up on this post shortly).
In my opinion, the FDA showed similar weakness in response to the Avandia hype. As I have blogged previously, based on data they had at the time, and even more recent data, the risk of heart attacks and Avandia just doesn't seem to be true. Yet, the FDA changed its label, scaring and confusing patients and physicians. (The recent recommendations about approval of future diabetes drugs are similar actions).
Bottom Line
One thing that shouldn't be overlooked is that despite my opinion that the boxed warning is likely unnecessary and unhelpful, quinolone antibiotics are over-prescribed. A once powerful drug, many bacteria are now resistant to Cipro because of over-use. Newer generations of fluroquinolones are likely similarly over-prescribes (as are antibiotics in general). That said, there are some conditions mild (uncomplicated urinary tract infections) and more serious (pneumonia) where therapy is appropriate. In those cases, these medications should be used. The boxed warning should be taken into consideration (consider alternatives for elderly and immunosuppressed patients and/or warn appropriately), but for the general public, tendinitis and tendon rupture was so rare, even by Public Citizen's numbers, that this should still be considered a rare adverse event.
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