Wednesday, April 30, 2008

Allergies: Yogurt or Singulair?

Given that it is the allergy season, two recent headlines suggested that I blog about allergies.
Allergies are nothing to sneeze at. Allergic Rhinitis (nasal allergies) affects about 40 million Americans, cause about 4 million missed days from work or school, and cost about 8 billion dollars a year.

The first headline was from ABC news, that discussed a Finnish study that gave probiotics (healthy bacteria that can be found in certain yogurts), to pregnant women who had allergies or whose husband had allergies, since their child would be genetically predisposed to developing allergies. The infants whose mothers got the priobiotics had 30% less chance of getting eczema, which is an allergic skin condition. The study is intriguing and goes along with they "hygiene hypothesis" which suggests that since we now live in a much cleaner environment, our immune system is not stimulated enough when we are infants and children, and this leads to allergies later in life. Probiotics are generally safe and have been found helpful in other conditions. Not sure I am ready to recommend this to all pregnant women with an allergy history.

A second story, that did not seem to get a lot of attention but to me was very interesting is the announcement that The Food and Drug Administration has turned down an application by Merck and Schering-Plough to combine the drugs they make, Singulair and Claritin respectively, into one pill. It is somewhat surprising to me that they would try this again since previous attempts to combine the pills have failed and since Claritin and Zyrtec are now over the counter (and Allegra is now generic), it would seem to me difficult for insurance companies to approve a combo pill, which would likely be expensive.

More on Allergic Rhinitis
There are several treatments for nasal allergies:
Non-sedating antihistamines: Claritin, Zyrtec, Allegra
Leukotriene modifiers: Singulair
Inhlaed nasal steroids: Flonase (fluticasone), Rhinocort, Nasacort, Veramyst
Inhaled nasal antihistamines: Asteline

There are muliple studies that show that fluticasone (Flonase) is better than Singulair, better than Claritin, and several studies that show that the combination of Singulair and Claritin is not better than either agent alone. However, in one study, though the combination of Singulair and Singulair was better than either agent alone, the individual agents were no better than placebo. In another study, Flonase was not only better than the combination of Singulair/Claritin or either alone, but for night time allergy symptoms both the combination Singulair/Claritin or Claritin alone was no better than placebo.

An excellent review by Dr. Robert Nathan showed that "leukotriene receptor antagonists (Singulair) are sometimes more effective than placebo, are no more effective than nonsedating antihistamines (Claritin) , and are less effective than intranasal corticosteroids in the treatment of allergic rhinitis." -my parenthesis and bolds

In other words, the non-sedating antihistamines do work some, Singulair is really no better than the non-sedating antihistamines , and the inhaled nasal steroids are clearly the best agents.

A recent guideline from World Health Organization suggests that for patients with mild, intermittent allergic rhinitis; treatment with non-sedating antihistamines and leukotriene modifiers were both acceptable forms of treatment, but patients with more chronic or bothersome symptoms, inhaled nasal steroids should be used.

Bottom Line: If you are an allergy sufferer, and you have symptoms that don't really bother you that much, and you don't get symptoms regularly, an as needed pill is a good option. Since prescription Singulair is really no better than over the counter Zyrtec or Claritin (and their generic equivalents), either of these non-sedating antihistamines should be fine. Patients with more chronic or bothersome symptoms should use an inhaled nasal steroid like fluticasone (generic for Flonase).

Friday, April 18, 2008

Glucose monitors of limited value in Type 2 Diabetes

Don't you just love Wilford Brimley. He seems so honest and trustworthy. When he tells you about ordering your diabetes supplies from Liberty, you just want to go out and get them, even if you don't have diabetes. Turns out, many diabetics probably don't need or even shouldn't test the blood sugars, as two recent studies indicate.
This shouldn't surprise us. Even in the latest diabetes guidelines on self monitored blood glucose (SMBG) from the the American Diabetes Association states:

"SMBG should be carried out three or more times daily for patients using multiple insulin injections or insulin pump therapy. (Stong Evidence)
For patients using less frequent insulin injections, noninsulin therapies, or medical nutrition therapy (MNT) alone, SMBG may be useful in achieving glycemic goals. (Weak Evidence)"

Fortunately, the majority of diabetics in this country (including the elderly) have type 2 diabetes, which often does not require insulin.

There were two studies published in BMJ today. The first looked at
184 patients less than 70 with newly diagnosed type 2 diabetes who were not on insulin and randomised them to self monitoring or no monitoring (control) groups for one year with follow-up visits every 3 months. At the end of the year, diabetes (as measured by the HbA1c) was no better in the self monitoring group. The second study looked 453 patients with type 2 diabetes who were also not on insulin, and split them up into no monitoring, less intense monitoring, and more intense monitoring. Not only did SMBG not improve diabetes control, but it also cost more and more importantly, decreased quality of life.

Glucose monitors are very useful in patient who do take insulin. I would also add that they can be useful for some patients who are not on insulin but are prone to low blood sugar (hypoglycemia), specifically patients taking sulfonylurea medications. However, many of the type 2 diabetics we see can be managed effectively with diet, exercise and one or several oral medications without the need for pricking their finger and testing their sugars all the time. In addition to Wilford, there are other commercials (Bayer) that promote glucose monitors as if they were both easy and essential. Whether it is a pill, device or even blood sugar monitor that someone is trying to sell you; make sure there is evidence to back it up.

Tuesday, April 8, 2008

Zetia In, Vytorin Out

As I said in my post last week, the now published ENHANCE study does not mean that Zetia is a bad drug, but that combining this drug with a statin (which is what Vytorin is) should not be used as first line therapy and adding to a statin when LDL goals are not met, may be beneficial.
Now, we have some evidence that this is in fact the case.
The SANDS study, reported in today's Journal of the American Medical Association shows that starting with a statin, and then adding Zetia improved atherosclerosis in diabetic patients treated to more aggressive LDL goals.
Bottom Line: If you have high cholesterol, your doctor says it needs to be lower, and diet and exercise won't get it down; first take a statin. If you can't take a statin or if a high dose statin can't get you to goal, then taking or adding Zetia is appropriate. If you get side effects with higher doses of statins, take the highest dose you can tolerate, then add Zetia if needed.
There is now really no good reason to ever start taking Vytorin. Though if you are on Vytorin, you should talk with your doctor before stopping.

For those who want more info:
The SANDS study looked at more aggressive goals for LDL (bad) cholesterol and blood pressure in patients with diabetes who are at very high risk for heart attacks and strokes. The took about 500 diabetic patients and half were treated to standard targets (LDL <100) and a systolic blood pressure (top number, SBP) of 130 mm Hg or lower. The other half was treated more aggressively to an LDL of 70 or lower and SBP of 115 mm Hg or lower. To look at progression of atherosclerosis (plaque build up), they measured by common carotid artery intimal medial thickness (IMT). The study showed that standard care group and progressive thickening of their arteries, but the aggressively treated group actually had regression or improvement. Unfortunately, there were no differences in deaths or heart attacks, but the rate of both were much lower than expected in the "normal" group, and it is possible that following these patients for a longer period of time will eventually show a difference.
The relation to Vytorin/Zetia is that in order to achive these more agressive blood pressure and cholesterol goals, more drugs were needed, including Zetia. More patients in the aggressive group got Zetia added to their statin medication, which was used first in both groups.

The ENHANCE trial also looked at the same outcome as SANDS, the CIMT.
In ENHANCE there was no improvement in CIMT when patients with very high cholesterol were given Zocor (simvistatin) 40mg or Zocor 40mg plus Zetia (Vytorin), even though Vytorin did lower the ldl more than the Zocor alone. This study got a lot of publicity for a number of reasons, but from a scientific standpoint it called into question the use of LDL as a target for cholesterol lowering. In addition to the multiple studies that show lowering LDL with a statin leads to fewer heart attacks and strokes, the SANDS study seems to confirm that LDL is indeed important, but in light of ENHANCE, how you get there is critical. You need to lower the LDL with a statin, but if you can not achieve LDL goals with a statin, you should add another medication like Zetia. The SANDS study is also important, because is suggests that patient with diabetes should be treated even more aggressively than current standards.

Zetia In, Vytorin Out.
Simvistatin, which is now generic, may be appropriate for many patients. However, it is not the most powerful statin. Newer drugs like Lipitor and Crestor are much more potent (and have CIMT, IVUS and other strong data to support preventing and even reversing atherosclerosis). At maximum dose, simvistatin 80mg can reduce LDL cholesterol by less than half, where as Lipitor and Crestor can achieve this at 20mg and 10mg respectively. Also, the higher the dose (regardless of potency) of a statin, the higher the chance of side effects. Thus, if you need your LDL reduced more than 40%, simvistatin is not likely going to be able to do this. In this situation, more potent statins such as Crestor and Lipitor should be used (as opposed to adding Zetia or starting with/switching to Vytorin which will decrease the LDL to goal, but may not lead to actual changes in the arteries). If a more potent statin can not achive LDL goals at a lower dose, a higher dose should be used. If this doesn't work (based at least on the diabetic patients in SANDS), then Zetia should be added since benefit was shown. Thus,
There is now really no good reason to ever start taking Vytorin.