The skeptical cardiologist recently prescribed ezetimibe to a patient who was leery of taking statin drugs for her elevated cholesterol. In the past she had taken red yeast rice in the belief that this was a safe and natural way to lower her cholesterol. I told her that I had looked into and researched red yeast rice (and wrote about it here), and that it was neither safe nor effective.
When I saw her back at our next office visit, she informed me that she had done her own research. She had gone on the internet and Googled ezetimibe and based on its “reviews” she felt it was an unsafe and dangerous drug.
It occurred to me at that point that patients like Ms X may actually believe that they can get reliable information on drug side effects and efficacy by going to a website where patients leave reviews on drugs they have taken.
Yelp For Medications
Such sites would be the equivalent of Yelp, which the wife of the skeptical cardiologist utilizes extensively to determine which restaurants we should patronize.
Lo and behold, if one Googles “reviews Zetia” a whole host of websites pop up offering you the opinions of random individuals on the drug.
On Everday Health Zetia gets 2 stars from 34 reviews with the most recent review being quite negative;
I hadRated Zetia for Rheumatoid Arthritis Report BEWARE. My husband took Zetia along with stantin, Crestor. Within a week, his leg muscles inflamed and shut down his kidneys and liver. He has been in the hospital for over a month and his condition has not improved. He’s on dialysis and can not walk. He is an alcoholic and his liver failed with Zetia.
Low dose of Zetia ….After just first days had severe diarrhea, halfed the dose. After a month I started seeing flashes in my right eye. Lots of eye fatigue, now a lot of ‘floaters’ in my right eye. Got checked by eye doctor to make sure it wasn’t optical nerve damage. Scarey. Coincidence? Don’t think so.
Limitations of The Yelp Concept In Assessing Medications
I empathize with and totally respect my patient’s desire to do her own independent research on the potential side effects of a drug that she will be putting in her body.
However, the Yelp approach just does not work well for medications.
There are three problems with relying on these kinds of patient-reported medication side effects.
The first is that the patients who leave comments on these sites are not representative of the overall pool of patients receiving the drug. Patients who feel they have been harmed in some significant way are much more likely to be motivated to spend the time recording what happened to them than are the individuals who felt fine after taking the drug.
There were 4 million prescriptions for ezetimibe written in 2015 and the number of patients leaving comments on these patient-review websites at most number in the hundreds. Thus, 99.9% of those taking ezetimibe are being silent, most likely because they are doing fine with the drug.
Secondly, most of the side effects reported by patients after taking ezetimibe occur at about the same frequency in those who take a placebo.
Although the package insert for ezetimibe lists various “common” side effects of the drug (such as diarrhea and upper respiratory infection), this table from the same package insert shows that such ailments are about as common in the group taking placebo.
The manufacturer, following FDA guidelines, reports out adverse reactions that are more common than 2% and numerically greater than placebo, but these are not necessarily significant differences.
Thus, we see that 4.1% of patients taking Zetia had diarrhea, but also that 3.7% of patients taking placebo had diarrhea.
If you take any group of several thousand individuals and follow them for a couple of months, probably 4% will get diarrhea whether or not they are taking ezetimibe.
The Nocebo Effect
Finally, we have to take into account the nocebo effect. The opposite of the placebo effect, in which inert substances make patients feel better, the nocebo effect makes patients who believe a drug will have side effects much more likely to experience those side effects.
The nocebo effect is quite common in patients who have read very negative comments on the internet about statin side effects. It is clear to me that this statin-related nocebo effect has also influenced patients taking non-statin cholesterol lowering medications like ezetimibe.
This is such an important factor in how patient’s tolerate ezetimibe that I spend considerable time during office visits emphasizing that ezetimibe works in a totally different way than statins, and is not associated with muscle aches/myalgias.
Alas, my patient has chosen to rely on the Yelp approach to deciding which medications to take. I’ve given her the best information I could on the safety and efficacy of ezetimibe based on my years of prescribing it and studying it. At this point it is her decision to make, and I accept it and we move forward managing her cardiovascular disease with the other tools in my toolkit.
Unlike an inaccurate restaurant review, however, a single individual describing inaccurately horrific side effects of a medication has the potential to steer thousands of patients away from potentially life-saving therapy.
There is still no reason to take over the counter fish oil supplements.
In fact, a study published Saturday found that fish oil supplementation (1 g per day as a fish-oil capsule containing 840 mg of n−3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]
did not result in a lower incidence than placebo of the primary end points of major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type.
However, another study published Saturday (REDUCE-IT) and presented at the annual American Heart Association Scientific Sessions to great fanfare found that an ethyl-ester formulation (icosapent ethyl) of eicosapentanoic acid (EPA, one of the two main marine n-3 fish oils) reduced major cardiovascular events by 25% in comparison to placebo.
When I wrote about Icosapent ethyl (brand name Vascepa) in a previous blog post in 2015 there was no data supporting its use:
A fish oil preparation, VASCEPA, available only by prescription, was approved by the FDA in 2012.
Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides(>500 mg/dl).
This is a very small market compared to the millions of individuals taking fish oil thinking that it is preventing heart disease.
The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.
Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.
After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.
Data do not exist to say that lowering triglycerides in the mild to moderate range by any drug lowers heart attack risk.
In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amarin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.
Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amarin, has stock in the company (Vascepa is the sole drug made by Amarin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amarin.
If he answers no to all of the above then, hopefully, your triglycerides are over 500.
And although elevated triglycerides confer an elevated CV risk nearly all prior trials evaluating different kinds of triglyceride-lowering therapies, including extended-release niacin, fibrates, cholesteryl ester transfer protein inhibitors, and omega-3 fatty acids have failed to show reductions in cardiovascular events
REDUCE-IT, Amarin trumpeted widely in September (before the actual data was published) now provides impressive proof that it prevents cardiovascular disease. Has the skeptical cardiologist changed his mind about fish oil?
Vascepa Is Not Natural Fish Oil
Although Amarin’s marking material states “VASCEPA is obtained naturally from wild deep-water Pacific Ocean fish” the active ingredient is an ethyl ester form of eicosapentoic acid (EPA) which has been industrially processed and distilled and separated out from the other main omega-3 fatty acid in fish oil (DHA or docosohexanoieic acid).
Natural fish oil contains a balance of EPA and DHA combined with triacylglycerols (TAGS).
So even if the REDUCE-IT trial results can be believed they do not support the routine consumption of over the counter fish oil supplements for prevention of cardiovascular disease.
Does REDUCE-IT Prove The Benefit of Purified High Dose EPA?
REDUCE-IT was a large (8179 patients) randomized, double-blind placebo controlled trial
Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter and had been receiving a stable dose of a statin for at least 4 weeks. In 2013 the protocol was changed and required a triglyceride level>200 mg/dl.
Participants were randomized to icosapent ethyl (2 g twice daily with food [total daily dose, 4 g]) or a placebo that contained mineral oil to mimic the color and consistency of icosapent ethyl and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group.
More importantly, the hard end-points of CV death, nonfatal stroke and heart attack were also significantly lower in the Vascepa arm compared to the “placebo” arm.
These results are almost unbelievably good and they are far better than one would have predicted given only a 17% reduction in triglycerides.
This makes me strongly consider prescribing Vascepa (something I heretofore have never done) to my higher risk patients with triglycerides over 200 after we’ve addressed lifestyle and dietary contributors.
Perhaps the high dose of EPA (4 grams versus the 1 gram utilized in most trials) is beneficial in stabilizing cell membranes, reducing inflammation and thrombotic events as experimental data has suggested.
Lingering Concerns About The Study
Despite these great results I have some concerns:
The placebo contained mineral oil which may not have been neutral in its effects. In fact, the placebo arm had a significant rise in the LDL cholesterol.
Enrolled patients were predominantly male and white. No benefit was seen in women.
Higher rates of serious bleeding were noted in patients taking Vascepa
Atrial fibrillation developed significantly more often in Vascepa patients (3.1%) versus the mineral oil patients (2.1%)
Finally, the trial was sponsored by Amarin Pharma. This is an aggressive company that I don’t trust. The steering committee consisted of academic physicians (see the Supplementary Appendix), and representatives of the sponsor developed the protocol, and were responsible for the conduct and oversight of the study, as well as the interpretation of the data. The sponsor was responsible for the collection and management of the data. All the data analyses were performed by the sponsor,
After i wrote my negative piece on Vascepa in 2015 a number of Amarin investors attacked me because Vascepa is the only product Amarin has and any news on the drug dramatically influences its stock price. Here is the price of Amarin stock in the last year.
The dramatic uptick in September corresponds to the company’s announcement of the topline results of REDUCE-IT. Since the actual results have been published and analyzed the stock has dropped 20%.
High Dose Purified and Esterified EPA-Yay or Nay?
I would love to see another trial of high dose EPA that wasn’t totally under the control of Amarin and such trials are in the pipeline.
Until then, I’ll consider prescribing Amarin’s pills to appropriate patients* who can afford it and who appear to have significant residual risk after statin therapy*.
But, I will continue to tell my patients to stop paying money for useless OTC fish oil supplements.
N.B.* Appropriate patients will fit the entry criteria for REDUCE-IT described below.
Patients could be enrolled if they were 45 years of age or older and had established cardiovascular disease or were 50 years of age or older and had diabetes mellitus and at least one additional risk factor. Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter (1.69 to 5.63 mmol per liter) and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter) and had been receiving a stable dose of a statin for at least 4 weeks;
So either secondary prevention (prior heart attack or stroke) or primary prevention in patients with diabetes and another risk factor.
The skeptical cardiologist has been utilizing coronary artery calcium (CAC) scans to help decide which patients are at high risk for heart attacks, and sudden cardiac death for the last decade. As I first described in 2014, (see here) those with higher than expected calcium scores warrant more aggressive treatment and those with lower scores less aggrressive treatment.
Although , as I have discussed previously, CAC is not the “mammography of the heart” it is incredibly helpful in sorting out personalized cardiovascular risk. We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of atherosclerotic cardiovascular disease (ASCVD) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals don’t need statin therapy.
Previously, major guidelines from organizations like the AHA and the ACC did not recommend CAC testing to guide decision-making in this area. Consequently, CMS and major insurers have not covered CAC testing. When my patients get a CAC scan they pay 125$ out of their pocket.. For the affluent and pro-active this is not an obstacle, however those struggling financially often balk at the cost.
I was, therefore, very pleased to read that the newly updated AHA/ACC lipid guidelines (full PDF available here) emphasize the use of CAC for decision-making in intermediate risk patients.
For those patients aged 40-75 without known ASCVD whose 10 year risk of stroke and heart attack is between 7.5% and 20% (intermediate, see here on using risk estimator) the guidelines recommend “consider measuring CAC”.
If the score is zero, for most consider no statin. If score >100 and/or >75th percentile, statin therapy should be started.
I don’t agree totally with this use of CAC but it is a step forward. For example, how I approach a patient with CAC of 1-99 depends very much on what percentile the patient is at. A score of 10 in a 40 year old indicates marked premature build up of atherosclerotic plaque but in a 70 year old man it indicates they are at much lower risk than predicted by standard risk factors. The first individual we would likely recommend statin therapy and very aggressive lifestyle changes whereas the second man we could discuss taking off statins.
Neil Stone, MD, one of the authors of the guidelines was quoted as saying that the imaging technique is “the best tiebreaker we have now” when the risk-benefit balance is uncertain.
“Most should get a statin, but there are people who say, ‘I’ve got to know more, I want to personalize this decision to the point of knowing whether I really, really need it.’ … There are a number of people who want to be certain about where they stand on the risk continuum and that’s how we want to use it,”
Indeed, I’ve written quite a bit about my approach to helping patients “get off the fence” on whether or not to take a statin drug.
Full title of these new guidelines includes an alphabet soup of organization acronyms
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol
N.B. For your reading pleasure I’ve copied the section in the new guidelines that discusses in detail coronary artery calcium.
Two interesting sentences which I’ll need to discuss some other time
-When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years
–CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.
–In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram
-184.108.40.206. Coronary Artery Calcium
Substantial advances in estimation of risk with CAC scoring have been made in the past 5 years. One purpose of CAC scoring is to reclassify risk identification of patients who will potentially benefit from statin therapy. This is especially useful when the clinician and patient are uncertain whether to start a statin. Indeed, the most important recent observation has been the finding that a CAC score of zero indicates a low ASCVD risk for the subsequent 10 years (S220.127.116.11-1–S18.104.22.168-8). Thus, measurement of CAC potentially allows a clinician to withhold statin therapy in patients showing zero CAC. There are exceptions. For example, CAC scores of zero in persistent cigarette smokers, patients with diabetes mellitus, those with a strong family history of ASCVD, and possibly chronic inflammatory conditions such as HIV, may still be associated with substantial 10-year risk (S22.214.171.124-9–S126.96.36.199-12). Nevertheless, a sizable portion of middle-aged and older patients have zero CAC, which may allow withholding of statin therapy in those intermediate risk patients who would otherwise have a high enough risk according to the PCE to receive statin therapy (Figure 2). Most patients with CAC scores ≥100 Agatston units have a 10-year risk of ASCVD≥7.5%, a widely accepted threshold for initiation of statin therapy (S188.8.131.52-13). With increasing age, 10- year risk accompanying CAC scores of 1 to 99 rises, usually crossing the 7.5% threshold in later middle age (S184.108.40.206-13). When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years (S220.127.116.11-14–S18.104.22.168-16). CAC measurement has no utility in patients already treated with statins. Statins are associated with slower progression of overall coronary atherosclerosis volume and reduction of high-risk plaque features, yet statins increase the CAC score (S22.214.171.124-17). A prospective randomized study of CAC scoring showed improved risk factor modification without an increase in downstream medical testing or cost (S126.96.36.199-18). In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram (S188.8.131.52- 19). CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.
Downloaded from http://ahajournals.org by on November 11, 2018
from Grundy SM, et al.
2018 Cholesterol Clinical Practice Guidelines
If you have had a heart attack at an early age or one of your parents did but your standard risk factors for coronary heart disease are normal you should consider getting tested for Lipoprotein(a) or Lp(a).
The standard lipid profile that most patients get checks LDL (bad) HDL (good) and total cholesterol along with triglycerides. While these are useful, I have many patients who have normal standard values but have developed advanced coronary heart disease at an early age despite following a perfect lifestyle (not smoking, regular aerobic exercise, healthy diet.)
The skeptical cardiologist tests such patients for Lp(a) (pronounced LP little a) and it is quite frequently elevated.
For patients, these are the facts to know about Lp(a)
It is the strongest single inherited (monogenetic) risk factor for the early development of coronary artery disease, heart attacks and strokes.
In addition to increasing risk of atherosclerosis, high Lp(a) is strongly associated with the development of calcific aortic valve disease which can result in narrowing of the aortic valve and aortic stenosis.
Depending on the cut-off used up to one in five individuals may have elevated Lp(a)
Levels of Lp(a) can be measured with a simple blood test that should cost no more than 50 to 100$. This is not included in standard lipid or cholesterol testing.
Risk for heart attack starts to rise with levels above 30 mg/dl and Canadian guidelines from 2016 (see here)) consider >30 mg/dl to be a risk factor and they recommend measuring Lp(a) in those with a family history of premature CAD or those at intermediate risk.
The European Atherosclerosis Society (EAS, 2010), suggested levels of <50 mg/dl as optimal. The EAS advised measuring Lp(a) once in all patients with premature CVD.
As levels get even higher risk also rises as these graphs show
Treatment For High Lp(a)
The lifestyle changes (both exercise and diet) that improve bad and good cholesterol levels have no effect on Lp(a). Our best drugs, the statins, for reducing risk of heart attack and stroke also don’t lower Lp(a) levels.
Only niacin has been shown to reduce Lp(a) across broad populations but there is no evidence that Lp(a) lowering by niacin lowers cardiovascular risk so it cannot be recommended for treatment.(In the AIM-HIGH study niacin did not reduce cardiovascular events in patients with Lp(a) with levels>50 mg/dl, despite achieving a mean Lp(a) reduction of 39%.)
Cholesteryl ester transfer protein inhibitors which raise HDL levels also reduce lipoprotein(a) concentrations, but three such inhibitors have not shown a clinical benefit.
In fact, currently there are no studies showing that lowering Lp(a) with any drug will effectively lower the associated risk of heart attack, stroke and aortic stenosis.
In the not too distant future, effective therapies may emerge. There are promising newer agents (antisense oligonucleotides or ASOs) currently in clinical trials and in limited populations the PCSK9 inhbitors, mipomersen and estrogen have lowered Lp(a) levels.
Why Test For Lp(a)?
If we have no effective therapies that work by lowering Lp(a) why recommend testing for it?
I test Lp(a) for two reasons.
First, since it is inherited, patients with high levels should consider having first degree relatives tested for Lp(a) to identify those who are going to be at high risk. This provides an early warning of who in the family is most at risk for cardiovascular complications early in life. Such patients should be considered for early screening for subclinical atherosclerosis. In addition, they should be additionally motivated to do everything possible to reduce their elevated risk by lifestyle changes.
Second, I tend to recommend more aggressive cholesterol lowering in patients who have evidence for early plaque build up for atherosclerotic events early in life than I otherwise would be. I tend to agree with the approach diagrammed below:
With this approach for patients who have had events related to atherosclerosis or advanced CAC for age we work super aggressively on optimizing all risk factors. I try to lower LDL to <70 with statins and with the addition of ezetimibe or PCSK9 inhbitors if needed.
If the patient has more problems with atherosclerotic events despite optimizing risk factors and Lp(a) >60 mg/dl, some experts recommend using apheresis a technique which runs the patient’s blood through a filter which removes LDL and Lp(a). Personally, I have not sent any patients for apheresis and await better studies proving its benefit.
For those patients seeking more detailed information and references I recommend Dr. Siggurdson’s excellent post on Lp(a)
In the ongoing nutritional war between adherents of low-fat and low-carb diets, the skeptical cardiologist has generally weighed in on the side of lower carbs for weight loss and cardiovascular health.
DIETFITS is a really well done study which provides important insights into three huge questions about optimal diet:
Should we choose a low-fat or a low-carb diet for weight loss and cardiovascular health?
Do baseline insulin dynamics predict who will respond to low-fat versus low-carb diet?
Can we predict who will respond to low-fat versus low-carb by genetic testing?
The Details Of DIETFITS
Stanford investigators recruited 609 San Francisco area individuals between the ages of 18 to 50 years with BMI of 28 to 40 and randomized them to a “healthy” low-fat diet or a “healthy” low-carb diet.
During the first 8 weeks of the study, low-fat participants were instructed to reduce fat consumption to <20 gm/ day while the low carb participants were instructed to reduce digestible carbohydrate to <20 gms/day.
Then individuals were allowed to add back fats or carbs back to their diets in increments of 5 to 15 g/d per week until “they reached the lowest level of intake they believed could be maintained indefinitely.” Importantly no explicit instructions for energy restriction were given.
The “healthy” instructions for both groups were as follows
maximize vegetable intake
minimize intake of added sugar, refined flours and trans-fats
focus on whole foods that are minimally processed, nutrient dense and prepared at home whenever possible
Dietfits Outcomes-Diet And Weight
Total energy intake was reduced by 500-600 kcal/d for both groups
The low-fat vs the low-carb intake at 12 months was 48% versus 30% for carbs, 29 vs 43% for fat and 21 vs 23% for protein.
Mean 12 months weight change was -5.3 kg for low-fat vs 6-6.0 kg for low-carb which was not significantly different
There was no difference between groups in body fat percentage or waist circumference
Both diets improved lipid profiles and lowered blood pressure, insulin and glucose levels
LDL (bad cholesterol) declined more in the low-fat group whereas HDL (good cholesterol) increased more and triglycerides declined more in the low-carb group.
Thus both diets were successful for weight loss and both improved risk markers for cardiovascular disease after a year.
DIETFITS- Can Genes and Insulin resistance Predict Best Diet?
Surprisingly, the study found no significant diet-genotype interaction and no diet-insulin secretion interaction with weight loss.
This means that they could not predict (as many believed based on earlier studies) who will benefit from a low carb diet based on either currently available genetic testing or a generally accepted measure of insulin resistance.
As the authors point out, these findings “highlight the importance of conducting large, appropriately powered trials such as DIETFITS for validating early exploratory analyses.”
As you can imagine this study has led to quite an uproar and backlash from dedicated combatants in the macronutrient wars.
A reasoned summary and response from Andreas Eenfeldt, a low carb proponent can be found on his excellent low carb/keto Diet Doctor site here.
If I’m allowed to speculate, the reason that we did not see any major additional benefit from low carb in this study is that the groups ended up so similar when it came to bad carbs. The low-fat group ended up eating fewer carbs too (!) and significantly less sugar, while the low-carb group ended with a somewhat weak low-carb diet, reporting 130 grams of carbs per day.
Eenfeldt emphasizes that low-fat diets never “win” these macronutrient dietary skirmishes:
On the whole, this study adds to the 57 earlier studies (RCTs) comparing low carb and low fat for weight loss.
From a standing of 29 wins for low carb, zero for low fat and 28 draws, we now have 29 wins for low carb and 29 draws. The wins for low fat stay at zero.
Larry Husten at Cardiobrief.org in his analysis of the study quotes a number of experts including Gary Taubes, the low carb pioneering journalist
Taubes speculates “that the weight loss may have been similar not because any diet works if you stick with it and cut calories (one possible interpretation) but because of what these diets had in common — avoid sugar, refined grains, processed foods. Whether the low-carb arm would have done even better had Gardner kept their carbohydrates low is something this study can’t say. (And Ornish [low-fat diet proponent] would probably say the same thing about fat consumption.)”
The low-fat or vegan disciples seem to have had a muted response to this study. I can’t find anything from John McDougal , Dean Ornish, Caldwell Esselstyn or Joel Fuhrman.
Readers feel free to leave comments which link to relevant analysis from the low-fat proponents.
Dietfits-Perspective Of The Participants
Julia Volluz at Vox wrote a fascinating piece recently which involved interviewing some of the participants in this study.
She points out that although the average DIETFITS participant lost over 10 pounds, “Some people lost more than 60 pounds, and others gained more than 20 during the year.”
She obtained permission from the lead author, Christopher Gardner and interviewed “Dawn, Denis, Elizabeth*, and Todd — two low-fat dieters and two low-carb dieters — about their experiences of succeeding or faltering in trying to slim down”
I highly recommend reading the entire article for details but Volluz concludes
And that leads us to one of the burning mysteries of diets: how to explain why some people fail where others succeed — or the extreme variation in responses. Right now, science doesn’t have compelling answers, but the unifying theme from the four study participants should be instructive: The particulars of their diets — how many carbs or how much fat they were eating — were almost afterthoughts. Instead, it was their jobs, life circumstances, and where they lived that nudged them toward better health or crashing.
DIETFITS-Importance of “Healthy” Diet
Most likely the success of both of these diets is due to the instruction that both groups received on following a “healthy” diet. This guidance is remarkably similar to what I advocate and is something that combatants in the diet wars ranging from paleo to vegan can agree on.
The JAMA paper only provides the description I listed above but Volluz adds that participants were instructed to:
… focus on whole, real foods that were mostly prepared at home when possible, and specifically included as many vegetables as possible, every day … choose lean grass-fed and pasture-raised animal foods as well as sustainable fish ... eliminate, as much as possible, processed food products, including those with added sugars, refined white flour products, or trans-fats … prepare as much of their own food as possible. …
Indeed, if you want to see a very detailed description of the instructional process for participants check out the very detailed description of the methods here.
Yours in Health,
N.B. I was searching for a reasoned response to this study from the low fat camp and to my surprise came across this fascinating video featuring the lead author of the study, Christopher Gardner, on (no fat/vegan) John McDougal’s YouTube site. Gardner is clearly on the side of sustainable, local , ethical food consumption but to his credit, his research , publications and comments on DIETFITS don’t reveal this.
When the skeptical cardiologist trained in medicine and cardiology in the 1980s the standard protocol for obtaining a lipid profile (LDL and HDL cholesterol plus triglycerides) involved having the patient fast for >8 hours before the blood was drawn.
Beginning in 2009, however, various national organizations began recommending the use of nonfasting lipid profiles. In 2011 the American Heart Association endorsed the fasting lipid profile and shortly thereafter I began telling my patients they did not need to fast for these tests.
Old habits and ideas are hard to kill and to this day most of my patients think that fasting is a requirement. Lab personnel seem to be stuck in the past as well and I typically instruct my patients to lie if they are asked if they have eaten.
Science continued to progress in the field of cardiology in 2017. Some cardiology interventions were proven to be more beneficial (TAVR) and some less (coronary stents). A class of cholesterol lowering drugs had a big winner and a big loser. A supplement that many thought, based on observational studies, was crucial to prevent heart disease, turned out to be unhelpful. More evidence emerged that saturated fat is not a dietary villain.
From the skeptical cardiologist’s viewpoint, the following were the major scientific studies relevant to cardiology:
1. “Thousands of heart patients get stents that may do more harm than good”
Cardiologists have known for a decade (since the landmark COURAGE study) that outside the setting of an acute heart attack (acute coronary syndrome or ACS), stents don’t save lives and that they don’t prevent heart attacks.
Current guidelines reflect this knowledge, and indicate that stents in stable patients with coronary artery disease should be placed only after a failure of “guideline-directed medical therapy.” Despite these recommendations, published in 2012, half of the thousands of stents implanted annually in the US continued to be employed in patients with either no symptoms or an inadequate trial of medical therapy.
Yes, lots of stents are placed in asymptomatic patients. And lots of patients who have stents placed outside the setting of ACS are convinced that their stents saved their lives, prevented future heart attacks and “fixed” their coronary artery disease. It is very easy to make the case to the uneducated patient that a dramatic intervention to “cure” a blocked artery is going to be more beneficial than merely giving medications that dilate the artery or slow the heart’s pumping to reduce myocardial oxygen demands.
Stent procedures are costly in the US (average charge around $30,000, range $11,000 to $40,000) and there are significant risks including death, stroke and heart attack. After placement, patients must take powerful antiplatelet drugs which increase their risk of bleeding. There should be compelling reasons to place stents if we are not saving lives.
I, along with the vast majority of cardiologists, still recommended stents for those patients with tightly blocked coronary arteries and stable symptoms, which were not sufficiently helped by medications. ORBITA calls into question even this indication for stenting.
The ORBITA study investigators recruited 230 patients to whom most American cardiologists would have recommended stenting. These patients appeared to have a single tightly blocked coronary artery and had chest pain (angina) that limited their physical activity.
They treated the patients for 6 weeks with aspirin/statins/ and medications that reduce anginal symptoms such as beta-blockers, calcium-channel blockers or long-acting nitrates. At this point patients were randomized to receive either a stent or to undergo a catheteriation procedure which did not result in a stent, a so-called sham procedure.
The performance of a sham procedure was a courageous move that made the study truly double-blinded; neither the patients nor the investigators knew which patients had actually received a stent. Thus, the powerful placebo effects of having a procedure were neutralized.
Surprisingly, the study found that those patients receiving stents had no more improvement in their treadmill exercise time, angina severity or frequency or in their peak oxygen uptake on exercise.
ORBITA hopefully will cause more cardiologists to avoid the “oculo-stenotic” reflex wherein coronary artery blockages are stented without either sufficient evidence that the blockage is causing symptoms or that a medical trial has failed.
Although this was a small study with a very narrowly defined subset of patients, it raises substantial questions about the efficacy of coronary stenting. If ORBITA causes more patients and doctors to question the need for catheterization or stenting, this will be a very good thing.
2. Vitamin D Supplementation Doesn’t Reduce Cardiovascular Disease (or fractures, or help anything really).
One of my recurring themes in this blog is the gullibility of Americans who keep buying and using useless vitamins, supplements and nutraceuticals, thereby feeding a $20 billion industry that provides no benefits to consumers (see here and here).
Vitamin D is a prime player in the useless supplement market based on observational studies suggesting low levels were associated with increased mortality and cardiovascular disease
Despite well done studies showing a lack of benefit of Vitamin D supplementation, the proportion of people taking more than 1,000 IU daily of Vitamin D surged from just 0.3 percent in 1999-2000 to 18 percent in 2013-2014.
Most recently a nicely done study showed that Vitamin D supplementation doesn’t reduce the risk of heart disease.
In a randomized clinical trial that included 5108 participants from the community, the cumulative incidence of cardiovascular disease for a median follow-up period of 3.3 years was 11.8% among participants given 100 000 IU of vitamin D3 monthly, and 11.5% among those given placebo.
Aaron Carroll does a good job of summarizing the data showing Vitamin D is useless in multiple other areas in a JAMA forum piece:
Last October, JAMA Internal Medicine published a randomized, controlled trial of vitamin D examining its effects on musculoskeletal health. Postmenopausal women were given either the supplement or placebo for one year. Measurements included total fractional calcium absorption, bone mineral density, muscle mass, fitness tests, functional status, and physical activity. On almost no measures did vitamin D make a difference.
The accompanying editor’s note observed that the data provided no support for the use of any dose of vitamin D for bone or muscle health.
Last year, also in JAMA Internal Medicine, a randomized controlled trial examined whether exercise and vitamin D supplementation might reduce falls and falls resulting in injury among elderly women. Its robust factorial design allowed for the examination of the independent and joined effectiveness of these 2 interventions. Exercise reduced the rate of injuries, but vitamin D did nothing to reduce either falls or injuries from falls.
In the same issue, a systematic review and meta-analysis looked at whether evidence supports the contention that vitamin D can improve hypertension. A total of 46 randomized, placebo controlled trials were included in the analysis. At the trial level, at the individual patient level, and even in subgroup analyses, vitamin D was ineffective in lowering blood pressure.
Finally, if the Vitamin D coffin needs any more nails, let us add the findings of this recent meta-analysis:
calcium, calcium plus vitamin D, and vitamin D supplementation alone were not significantly associated with a lower incidence of hip, nonvertebral, vertebral, or total fractures in community-dwelling older adults.
3. PCSK9 Inhibitors: Really low cholesterol levels are safe and reduce cardiac events
I reported the very positive results for evolocumab and disappointing results for bosocizumab on the physician social media site SERMO in March but never put this in my blog.
As a practicing cardiologist I’ve been struggling with how to utilize the two available PCSK9 inhibitors (Amgen’s Repatha (evolocumab) and Sanofi’s Praluent (alirocumab) in my clinical practice. I would love to use them for my high risk statin-intolerant patients but the high cost and limited insurance coverage has resulted in only a few of my patients utilizing it.
The lack of outcomes data has also restrained my and most insurance companies enthusiasm for using them.
The opening session at this year’s American College of Cardiology Scientific Sessions in DC I think has significantly changed the calculus in this area with two presentations: the first showing Amgen’s “fully humanized” evolocumab significantly lowers CV risk in high risk patients on optimal statin therapy and the second showing that Pfizer’s “mostly humanized” bococizumab loses efficacy over time and will likely never reach the market.
The FOURIER study of evolocumab randomized 27, 564 high risk but stable patients who had LDL>70 with prior MI, prior stroke or symptomatic PAD to receive evolocumab or placebo on top of optimized lipid therapy. 69% of patients were recieving high intensity statin therapy and the baseline LDL was 92. LDL was reduced by 59% to average level of 30 in the treated patients. The reduction in LDL was consistent through the duration of the study.
IN 1/4 of the patients LDL was <20! These are unprecedented low levels of LDL.
Active treatment significantly reduced the primary endpoint by 15% and reduced the secondary endpoinf of CV death, MI, stroke by 20%. absolute difference 2% by 3 years.
There was no difference in adverse effects between placebo and Evo.
The next presentation featured data using Pfizer’s candidate in the PCSK9 wars and the acronym SPIRE (Studies of PCSK9 Inhibition and the Reduction in vascular Events (SPIRE) Bococizumab Development Program).
Paul Ridker presented the outcomes data for bococizumab which was actually similar to evolocumab data but given the declining efficacy and development of antibodies to the Pfizer drug over time these were very disappointing for Pfizer and I would presume their drug will never reach the market.
How will these results impact clinical practice?
I am now more inclined to prescribe evolocumab to my very high risk patients who have not achieved LDL< 70. I’m willing to do what I can to jump through insurance company hoops and try to make these drugs affordable to my patients.
I am less worried about extremely low LDL levels and have more faith in the LDL hypothesis: the lower the LDL the lower the risk of CV disease.
Cost is still going to be an issue for most of my patients I fear and the need for shared decision-making becomes even more important.
4. “Pure Shakes Up Nutritional Field: Finds High Fat Intake Beneficial.”
As one headline put it.
I recorded my full observations on this observational international study here
Here is a brief excerpt:
The Prospective Urban Rural Epidemiology (PURE) study, involved more than 200 investigators who collected data on more than 135000 individuals from 18 countries across five continents for over 7 years.
There were three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe)
This was the largest prospective observational study to assess the association of nutrients (estimated by food frequency questionnaires) with cardiovascular disease and mortality in low-income and middle-income populations,
The PURE team reported that:
-Higher carbohydrate intake was associated with an increased risk of total mortality but not with CV disease or CV disease mortality.
This finding meshes well with one of my oft-repeated themes here, that added sugar is the major toxin in our diet (see here and here.)
I particular liked what the editorial for this paper wrote:
Initial PURE findings challenge conventional diet–disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well designed randomised controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility
I wish for all those following science-based medicine a healthy dose of humility. As science marches on, it’s always possible that a procedure we’ve been using might turn out to be useless (or at least much less beneficial than we thought), and it is highly likely that weak associations turn out to be causally nonsignificant. Such is the scientific process. We must continually pay attention, learn and evolve in the medical field.
Happy New Year to Be from the Skeptical Cardiologist the EFOSC!
The Skeptical Cardiologist was recently contacted by a television reporter working on a segment about statins. and looking for a cardiologist to interview who “is concerned about the cognitive side effects of these drugs.”
Since I regularly prescribe statin drugs to my patients to reduce their risk of heart attack and stroke, I am very concerned about any possible side effects from them, cognitive or otherwise. However, in treating hundreds of patients with statins, I have not observed a consistent significant effect on brain function.
When the U.S. Food and Drug Administration (FDA) issued a statement in 2012 regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use it came as quite a surprise to most cardiologists.
The FDA made a change in the patient information on all statin drugs which stated:
Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken
This FDA statement was surprising because prior observational and randomized controlled trials had suggested that patients who took statins were less likely to have cognitive dysfunction than those who didn’t.
Early studies implied that statins might actually protect against Alzheimer’s disease.
In fact these signals triggered two studies testing if statins could slow cognitive decline in patients with established Alzheimer’s disease One study used 80 mg atorvastatin versus placebo and a second 40 mg simvastatin versus placebo and both showed no effect on the decline of cognitive function over 18 months.
More recently, multiple reviews and meta-analyses have examined the data and concluded that there is no significant effect of statins on cognitive function. Importantly, these have been written by reputable physician-scientists with no financial ties to the pharmaceutical industry.
Data Show No Evidence of Causality Despite Case Reports
The FDA added the warning to statin patient information based on case reports Occasional reports of patients developing memory loss on a statin do not prove that statins are a significant cause of cognitive dysfunction.
Case reports have to be viewed in the context of all the other scientific studies indicating no consistent evidence of negative effects of the statins. Case reports are suspect for several reasons:
First, patients receiving statins are at increased risk for memory loss because of associated risk factors for atherosclerosis and advancing age. A certain percentage of such patients are going to notice memory loss independent of any medications.
Second. The nocebo effect: If a patient taking a statin is told that the drug will cause a particular side effect,that patient will be more likely to notice and report that particular side effect.
A recent study in The Lancet looked at reported side effects in patients taking atorvastatin versus placebo and found substantial evidence for the nocebo effect.
Analysis of the trial data revealed that when patients were unaware whether they were taking a statin or a placebo, the number of side effects reported was similar in those taking the statin and those taking placebo. However, if patients knew they were taking statins, reports of muscle-related side effects in particular increased dramatically, by up to 41 per cent.
Third, a review of the FDA post-marketing surveillance data showed the rate of memory loss with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 per million prescriptions for statins , 1.6 per million prescriptions for losartan) and clopidogrel (1.9 per million prescriptions for clopidogrel.)
What Most Media Prefer: Controversy And Victims
I thought my experience and perspective on statins and cognitive function might be useful for a wider audience of patients to hear so I agreed to be interviewed. After I expressed interest the reporter responded:
I would like to interview you and also a person who has experienced memory and/or thinking problems that they attribute to statin use.
I responded with “let me see what I can find,” although I was concerned that this reporter was searching for a cardiologist to support attention-grabbing claims of severe side effects of statins rather than seeking a balanced, unbiased perspective from a knowledgeable and experienced cardiologist.
If I produced a “victim” of statin-related memory loss this would boost ratings.
I then began racking my brain to come up with a patient who had clearly had statin-related memory loss or thinking problems. I asked my wonderful MA Jenny (who remembers details about patients that I don’t) if she could recall any cases. Ultimately, we both came up without any patients for the interview. (Any patient of mine reading this with definite statin memory loss please let me know and I will amend my post. However, I won’t be posting anecdotes outside of my practice.)
I have had a few patients relate to me that they feel like their memory is not as good as it was and wonder if it could be from a medication they are on. Invariably, the patient has been influenced by one of the statin fear-mongering sites on the internet (or a friend/relative who has been influenced by such a site.)
I wrote about one such site in response to a patient question a while back:
The link appears to be a promotional piece for a book by Michael Cutler, MD. Cutler’s website appears to engage in fear-mongering with respect to statins for the purpose of selling his books and promoting his “integrative” practice. I would refer you to my post entitled “functional medicine is fake medicine”. Integrative medicine is another code word for pseudoscientific medicine and practitioners should be assiduously avoided.
The piece starts with describing the case of Duane Graveline, a vey troubled man who spent the latter part of his life attempting to scare patients from taking statins. Here is his NY Times obituary.
You can judge for yourself if you want to base decisions on his recommendations.
There is no scientific evidence to suggest statins cause dementia.
An Internet-Driven Cult With Deadly Consequences
Steve Nissen recently wrote an eloquent article which accuses statin deniers of being an “internet–driven cult with deadly consequences.” Nissen has done extremely important research helping us better understand atherosclerosis and is known for being a patient advocate: calling out drug companies when they are promoting unsafe drugs.
I have immense respect for his honesty, lack of bias, and his courage to be outspoken . He writes:
“Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search en- gine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled “The Grave Dangers of Statin Drugs—and the Surprising Benefits of Cholesterol”. We are losing the battle for the hearts and minds of our patients to Web sites de- veloped by people with little or no scientific expertise, who often pedal “natural” or “drug-free” remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity— or even worse, dementia.”
He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.
The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:
“The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administra-tion. The bill’s principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies.”
Dealing With Statin Side Effects In My Practice
When a patient tells me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I’ve concluded that in any individual patient, it is possible for any drug to cause side effects. And, chances are that if we don’t address the side effects the patient won’t take the medication.
If the side effect is significant I will generally tell the patient to stop the statin and report to me how they feel after two to four weeks.
If there is no improvement I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.
If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn’t prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.
At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or livalo.) If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.
For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long term therapy.
Today a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I’m sure there is a forum somewhere on the internet where patients have reported this). Fortunately he accepted my expert opinion and will continue taking the drug.
If the symptoms persist and the patient continue to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.
Since statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denials cult thus minimizing the nocebo effect
N.B. It turns out the reporter had an open mind about the issue of statin-related memory loss. We had a good discussion and at some point you may see the skeptical cardiologist on TV being interviewed on the topic.
I could bring to the interview one of my many patients who since starting to take statins have not had a heart attack or stroke and who have taken statins for decades without side effects.
Now that would make for some compelling and exciting TV!
In an earlier post the skeptical cardiologist introduced Geo, a 61 year old male with no risk factors for heart attack or stroke other than a high cholesterol. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.
His doctor had recommended that he take a statin drug but Geo balked at taking one due to concerns about side effects and requested my input. My first steps were to gather more information.
-I calculated his 10 year risk of stroke or heart attack at 8.4% (treatment with statin typically felt to benefit individuals with 10 year risk >7.5%) and as I have previously noted, this is not unusual for a man over age 60.
-I assessed him for any hidden or subclinical atherosclerosis and found
The vascular ultrasound showed below normal carotid thickness and no plaque and his coronary calcium score was 18, putting him at the 63rd percentile. This is slightly higher than average white men his age.
So Geo definitely has atherosclerotic plaque in his coronary arteries. This puts him at risk for heart attack and stroke but not a lot higher risk than most men his age.
Strictly speaking, since he hasn’t already had a heart attack or stroke, treating him with a statin is a form of primary prevention. However, we know that atherosclerotic plaque has already developed in his arteries and at some point, perhaps years from now it will have consequences.
What is the best approach to reduce Geo’s risk?
It’s essential to look closely at lifestyle changes in everyone to reduce cardiac risk.
The lifestyle components that influence risk are
Cigarette Smoking (by far the strongest)
Obesity (Obviously related to #1 and #2)
Patients who try to change to what they perceive as a heart healthy diet by switching to non-fat dairy and eliminating all red meat will not substantially lower risk (see here.) Even if you are possess the rock-hard discipline to stay on a radically low fat diet like the Esselstyn diet or the Pritikin diet there are no good data supporting their efficacy in preventing cardiac disease.
Geo was not far from theMediterranean diet I recommend but would probably benefit from increased veggie and nut consumption. He was not overweight and he doesn’t smoke. I encouraged him to engage in 150 minutes of moderate exercise weekly.
Low Dose, Intermittent Rosuvastatin
I engaged in shared decision-making with Geo. Informing him, as best I could, of the potential side effects and benefits of statin therapy.
After a long discussion we decided to try a compromise between no therapy and the guideline recommended moderate intensive dose statin therapy.
This approach utilizes a low dose of rosuvastatin taken intermittently with the goal of minimizing any statin side effect but obtaining some of the benefits of statin drugs on cardiovascular risk reduction.
I have many patients who have been unable to tolerate other statin drugs in any dosage due to statin related muscle aches but who tolerate this particular treatment and I see substantial reductions in the LDL (bad) cholesterol with this approach.
Studies have shown that rosuvastatin 5–10 mg or atorvastatin 10–20 mg given every other day produce LDL-C reduction of 20–40 %
Studies have also shown that In patients with previous statin intolerance, rosuvastatin administered once or twice weekly (at a mean dose of 10 mg per week) achieved an LDL-C reduction of 23–29% and was well tolerated by 74–80 % of patients.
In a recent report from a specialized lipid clinic, 90 % of patients referred for intolerance to multiple statins were actually able to tolerate statin therapy, although the majority was at a reduced dose and less-than-daily dosing.
Results in Geo
After several months of taking 5 mg rosuvastatin twice weekly Geo felt fine with no discernible side effects. He obtained repeat cholesterol levels:
His LDL had dropped 52% from 140 to 92.
Hopefully, this LDL reduction plus the non-cholesterol lowering beneficial properties of statins (see here) will substantially lower Geo’s risk of heart attack and stroke.
We need randomized studies testing long-term outcomes using this approach to make it evidence-based. But in medicine we frequently don’t have studies that apply to specific patient situations. In these cases shared decision-making in order to find solutions that fit the individual patient’s concerns and experience becomes paramount.
The skeptical cardiologist was shocked to hear from a patient last week that she would have to pay considerably more for generic rosuvastatin (GR) than Crestor, its brand name equivalent.
Crestor is the most potent statin we have at lowering LDL (bad) cholesterol, raising HDL (good) cholesterol, and preventing strokes and heart attacks. It is also the best tolerated statin in my experience; I use it frequently at low or intermittent dosages in patients who have developed muscle aches on other statins.
In comparison to atorvastatin (Lipitor, the most widely prescribed statin), Crestor is less likely to interact with other medications and (very important for a surprising number of my patients), you can consume grapefruit when taking it.
When a generic (rosuvastatin calcium) of Crestor became available last year I rejoiced, believing that the high cost of Crestor would now drop to the levels we have typically seen with other generic statins.
For example, when Lipitor (atorvastatin, the statin market leader for 20 years) went generic, patients no longer worried about its cost.
Initially it seemed GR was much more affordable for my patients than Crestor, however recently, I have had many of them report a rise in its cost.
Why Would The Generic Cost More Than Crestor?
The reasons for brand name versus generic pricing are many and complex, and they yield insight into the legal machinations that Big Pharma engages in to maintain high patient pharmaceutical costs.
This NY Times piece from July, 2016 reveals how hard AstraZeneca fought to protect its exclusivity in selling Crestor and to prevent generics from entering the market. AstraZeneca’s last tactic involved a lawsuit claiming that their patent was protected by the orphan drug act. They lost and were heavily criticized:
“This case is not about the medical needs of a small population of pediatric patients with a rare disease,” the F.D.A. and Justice Department said in a brief filed in the lawsuit. “It is about AstraZeneca’s profit-driven desire to substantially extend its virtual monopoly on one of the world’s most popular medicines.”
There are other factors that slow the drop in generic prices. Consumer Reports, writing on the anticipated release of GR in May quoted an expert thusly:
“While some pharmacies drop the price as generics enter the market, others will hold it near the brand-name price as long as possible.” They get away with it, he says, because many customers who have health insurance pay a set co-pay regardless of the retail price. But those consumers who pay the entire cost of the drug themselves because they don’t have insurance or have a high deductible may not see the substantial savings that should come with generic availability.”
What an individual pays for drugs varies wildly depending on their insurance coverage. These costs are extremely hard for a physician to anticipate and rarely reflect the actual cost of drugs. Thus, in America, patients as consumers are often isolated from the true costs of pharmaceuticals to society.
I did not pay anything for the 25 pills, however the paperwork states a cost of $220 if I had to buy this outside of a health insurance plan. Do you know if the health insurance company is being charged the $220, or do they negotiate a lower cost with the manufacturer?
I don’t have that answer, but would love to know it. This kind of information is hard to get at.
Send Me Your Observations On The Cost of Generic Rosuvastatin
I would like to get input from my patients and readers on their experience regarding the cost of GR to them and/or their insurance company.
I’d also appreciate input from those in the pharmaceutical or insurance portion of this equation (I know I have at least one patient who is in the pharmaceutical industry).
Finally, if any of you have experience with purchasing GR online from international pharmacies, please share it below. For example, this site claimed in May, 2016: