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Saturday, February 1, 2014

Should you be on cholesterol medication? How the new guidelines are different

Cardiovascular disease—including coronary atherosclerosis and cerebrovascular disease, remains the number one cause of mortality in the United States. One out of three people in this country will die of cardiovascular causes.  Although I can’t say that the other top causes of mortality are particularly attractive--cancer, chronic lung disease, accidents and dementia—premature cardiovascular death can certainly be very devastating and it makes sense to do our best to prevent it.

In November 2013 updated guidelines for the treatment of high cholesterol were released by the American College of Cardiology-American Heart Association.  These guidelines were the subject of significant controversy. In contrast to the previous guidelines from 2002, the current guidelines do not suggest treatment based primarily on numerical cholesterol targets. Rather, the guidelines stratify people according to determined cardiovascular risk and recommend either high intensity statin treatment, moderate intensity statin treatment, or no statin treatment. The guidelines do not support using other types of cholesterol-lowering drugs because at this point there is not good data to suggest that using other types of treatments is beneficial in terms of preventing actual cardiovascular outcomes (heart attack, stroke or cardiovascular death). This is despite the fact that there are treatments out there that do lower one’s cholesterol numbers.
How is cardiovascular risk determined? With the new guidelines, a new risk calculator was proposed. In my clinical practice in the past I’ve used the Framingham Risk Calculator and the Reynolds Risk Calculator . The new risk calculator released with the 2013 guidelines is a bit different. Some experts have suggested that it overestimates risk. With the new risk calculator, if one’s ten year risk of a cardiovascular event exceeds 7.5% then treatment with a statin is recommended.

The new guidelines divide people into the following groups of patients between ages 40 and 75 years who are in need of treatment with statins, or so called “statin benefit groups.”

·         Those with LDL over 190mg/dL (high intensity statin treatment is recommended)

·         Those with a ten year risk of >7.5% (moderate intensity statin treatment is recommended)

·         Those with established cardiovascular disease (high intensity statin treatment is recommended)

·         Those with diabetes, in which 10 year risk is >7.5% (high intensity statin treatment is recommended)

·         Those with diabetes, in which 10 year risk is <7 .5="" font="" intensity="" moderate="" statin="">treatment is recommended)
Click here to calculate your risk. What qualifies as high intensity statin treatment? LDL lowering of 50% or greater. What is moderate intensity statin treatment? LDL lowering of 30-50%.
The guidelines suggest that particular statins may be better than others at achieving these goals and good outcomes: atorvastatin, simvastatin, and rosuvastatin.  Other statins are typically used when patients experience unwanted side effects, like muscle pain.

How are things different with the new guidelines?
Let’s take an example.    A 71 year old white female, non-smoker, non-diabetic, with a history of hypertension, asked me whether or not she should be treated for high cholesterol.  She is concerned about her risk of heart disease, as her mother had a stroke in her 60s and then sudden death, presumed cardiovascular, at age 83. My patient’s most recent total cholesterol level was 204 mg/dL with an LDL level of 121 mg/dL and an HDL level of 64 mg/dL.  A couple of years ago I calculated her Framingham Risk score, which is 6% with these risk factors. This represents low to intermediate risk. To get further information I also ordered a coronary calcium score, which was found to be zero.  Last year, based on these numbers and the older guidelines, I recommended against treatment with a statin.  However, now, based on the new risk assessment tool, the same patient has a ten year risk of 16%.  With the new guidelines she would unequivocally qualify for moderate dose statin.   At this point, I am not exactly sure what to do with the coronary calcium score, which probably projects that her risk is lower than the 16% that the new equation came up with.  Nonetheless, I am not sure that coronary calcium scoring entirely predicts all cardiovascular risk—for example risk related to small vessel disease and stroke, so perhaps she should receive treatment.  Low dose, statin treatment might be a good compromise here.

Interestingly, based on this new risk calculator virtually every 71 year old, even with optimal risk factors, would qualify for treatment with a statin.  Herein lies the controversy with this tool.
Nonetheless, my own view of the new guidelines is mostly favorable. To me it simplifies things based on what we know from numerous well designed studies. Treatment, with an emphasis on statins, is based on risk projection and less attention is paid to absolute numbers.  I hope that the next decade will continue to bring more a nuanced understanding of risk.






Thursday, August 22, 2013

Should a Doctor Prescribe Drugs that are Unapproved by the FDA ?

Here’s an interesting clinical dilemma brought to my attention by another physician.
She was asked to refill a prescription for a drug called domperidone to help a patient with lactation. Domperidone is not FDA approved in the United States for any indication. However, in Europe and in Canada it is approved as a promotility agent for patients with a condition called gastroparesis, which causes the stomach to empty very slowly and results in chronic nausea and vomiting. As a side effect the drug is also known to increase the production of prolactin, a hormone that stimulates milk production. In the case of this physician's patient, she had adopted a child and found that the medication had effectively enabled her to produce milk and nurse, with seemingly no untoward effects. It’s unclear who had initially prescribed the drug, but various online lactation support forums discuss it as an option  for women who have trouble with lactation.
The questions: Is it legal, ethical or good medical practice for a physician in the United States to write a prescription for domperidone for a patient who has been using it for lactation with good results? How about for gastroparesis? Where does one get the drug? Is it even legal to sell the drug in the United States? 
I’ve cared for at least two patients who have used domperidone. In both instances it was ordered by prescription from an overseas source by a local gastroenterologist. In these two cases my patients had tried just about everything on the market in the United States for gastroparesis and were still struggling with debilitating symptoms. In one case, my patient had required hospitalizations and ultimately a feeding tube because of intractable vomiting. The drug was ineffective in both patients and it was eventually discontinued. 
As I read more about this medication I discovered that the FDA cautions:  
"FDA warned healthcare professionals and breastfeeding women not to use an unapproved drug, domperidone, to increase milk production (lactation). The agency is concerned with the potential public health risks associated with domperidone. FDA took these actions because it has become aware that some women are purchasing this drug from compounding pharmacies and from foreign sources. Although domperidone is approved in several countries outside the U.S. to treat certain gastric disorders, it is not approved in any country, including the U.S., for enhancing breast milk production in lactating women and is also not approved in the U.S. for any indication.”
The concern over domperidone is its potential to induce potentially fatal cardiac arrhythmias through QT prolongation (an alteration of electrical activity in the heart). This risk has been recognized in Europe and is currently under study. Nonetheless, at least one expert panel in Canada has endorsed the safety of the drug for use in lactation (though not currently approved for this use in Canada). 
As my colleague and I discussed the situation with her patient we both concluded that it would not be prudent to refill this prescription for the purpose of lactation. In fact, it would likely be construed as medical malpractice, in light of the drug’s status with the FDA, should the patient or her baby suffer any toxicity. However, clearly there are gastroenterologists who feel that prescribing this medication in United States for cases of severe gastroparesis is justifiable—and I would concur that in certain situations this might be a compassionate and reasonable option despite the regulatory concerns.   
To further extend this discussion—physicians do frequently prescribe drugs that are on the market and FDA approved for off-label use. For example, just yesterday I prescribed gabapentin for hot flashes. One interesting study published in Archives of Internal Medicine in 2006 by Radley, Finkelstein, and Stafford found that 21% of sampled medications were being prescribed for off-label use. 
The authors concluded:
"The Food and Drug Administration (FDA) focuses on market entry for prescription drugs rather than regulating physicians' prescribing practices, allowing off-label use of medications for indications beyond those formally evaluated by the manufacturer. Off-label prescribing of medications is legal,1 often thought to be supported by scientific evidence,2 and common in certain clinical settings.3- 4 Although this practice provides a pathway to innovation in clinical practice, it raises key concerns about risks to patients and costs to the health care system.5- 7"
Whereas prescribing approved medications for off-label use falls into the realm of acceptable clinical practice, one has to be very circumspect about prescribing drugs that are not deemed adequately safe or effective to market in the United States for any indication. Unfortunately for those who feel that the FDA is too slow, political, or conservative in its approval process, these are the regulatory constraints under which physicians must practice in the United States.

Wednesday, July 3, 2013

What foods are in the Mediterranean Diet ?

The Mediterranean Diet is fresh on my mind, having recently returned from a trip to Turkey.  During my trip I became a particular fan of Turkish vegetables—white beans with tomatoes and onions in olive oil, oven baked green beans or okra, eggplant stuffed with walnuts with a tomato ragout, to name a few. My husband commented that I must be a true fan of olives, as he surveyed my breakfast plate, which was chalk full of several varieties of olives, raw cucumbers, tomatoes, a few arugula leaves, fresh cheese and bread.  During my travels I also enjoyed a variety of grilled fresh fish served with lemon, seaweed salad, pomegranate juice, freshly pressed at the side of road, and roasted chestnuts, also sold by street vendors.

I was elated to hear that a new study published in the New England Journal of Medicine in April of this year  validated the health benefits of the Mediterranean diet. The study randomized 7447 women and men with risk factors for cardiovascular disease to receive either a Mediterranean diet enriched with olive oil, a Mediterranean diet enriched with nuts, or a standard low fat diet for the control group. Participants assigned to the two Mediterranean diet arms were found to have a significantly reduced risk of adverse cardiovascular outcomes (heart attack, stroke, death from cardiovascular causes) compared with the control group. The study was terminated after a mean follow up time of 4.8 years.
 Are you wondering how your diet matches up with the “Mediterranean Diet” as defined by the recent study? I was after I read these results.
Here are the criteria with answers qualifying for the Mediterranean Diet shown in bold.
1. Do you use olive oil as main culinary fat?     Yes
2. How much olive oil do you consume in a given day (including oil used for frying, salads, out of house meals, etc.)?     4 or more tablespoons
3. How many vegetable servings do you consume per day? (1 serving = 200g - consider side dishes as 1/2 serving)     2 or more (at least 1 portion raw or as salad)
4. How many fruit units (including natural fruit juices) do you consume per day?     3 or more
5. How many servings of red meat, hamburger, or meat products (ham, sausage, etc.) do you consume per day? (1 serving = 100-150 g)     Less than 1
6. How many servings of butter, margarine, or cream do you consume per day? (1 serving = 12 g)     Less than 1
7. How many sweet/carbonated beverages do you drink per day?     Less than 1
8. How much wine do you drink per week?     7 or more glasses
9. How many servings of legumes do you consume per week? (1 serving = 150 g)     3 or more
10. How many servings of fish or shellfish do you consume per week?  (1 serving: 100-150 g fish, or 4-5 units or 200 g shellfish)     3 or more
11. How many times per week do you consume commercial sweets or pastries (not homemade), such as cakes, cookies, biscuits, or custard?     Less than 3
12. How many servings of nuts (including peanuts) do you consume per week? (1 serving = 30 g)     3 or more
13. Do you preferentially consume chicken, turkey or rabbit meat instead of veal, pork, hamburger or sausage?     Yes
14. How many times per week do you consume vegetables, pasta, rice, or other dishes seasoned with sofrito (sauce made with tomato and onion, leek, or garlic, simmered with olive oil)?      2 or more
Taking a closer look at the details of the study as described in the NEJM supplement, it seems to me that the particular factors of those listed above that really differentiated the Mediterranean groups from the control group were: the quantity of olive oil ingested, the increase in nuts consumed, and, somewhat less significantly, the amount of seafood consumed, legumes consumed, and sofrito sauce consumed.
In this study the particular kinds of nuts prescribed were walnuts, hazelnuts and almonds. However, there may be health benefits with other nuts as well. Here is some useful nutritional information from University of Michigan Health System (my alma mater) about nuts.
Personally, this study has changed my health practices. While I was already doing well with some of its components, since reading the specifics of the Mediterranean Diet prescribed and found to be associated with reduced cardiovascular risk I’ve made greater attempts to incorporate legumes, nuts, and fish into my diet.