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:
The father of the eternal fiancee’ of the skeptical cardiologist (FOEFOSC, let’s call him “Geo”) is a typical 61 year old white male. A year ago his primary care physician informed him that he needed to start taking a statin drug because his cholesterol was high. The note accompanying this recommendation also stated “work harder on diet and exercise to get LDL<130.” No particulars on how to change his current diet and exercise program were provided.
Neither of Geo’s parents and none of his siblings have had heart problems at an early age and Geo is very active without any symptoms. His diet is reasonably free of processed food and added sugar, he is not overweight and his blood pressures are fine. Due to concern about side effects he had read about on the internet and because he doesn’t like taking medications , Geo balked at taking the recommended statin,
Reluctance to start a new and likely life-long drug is understandable especially when combined with a constant stream of internet-based bashing of statins.
My advice was sought and I suggested a few things that would be helpful in making a more informed decision:
As I’ve pointed out before (here), the vast majority of men over the age of 60 move into a 10 year risk category >7.5%, no matter how great their lifestyle is, and Geo was no exception with a risk of 8.4%. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.
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.
When Geo presented these findings to his PCP, he seemed unaware of the ASCVD risk estimator (recommended by AHA/ACC guidelines first published in 2013), which no longer suggests LDL levels as goals. His PCP also seemed miffed that he had gotten the coronary calcium scan. Geo felt like the PCP’s attitude was “shut up and do what I tell you.”
Geo’s PCP’s approach exemplifies a not-uncommon traditional doctor-patient relationship, but a better approach is shared decision-making (see here). Geo, like many patients, welcomes more information on the risks and benefits of any recommended treatment so that he can participate in deciding the best course of action.
By giving patients more information on the risks, side effects, and benefits of the statin drugs along with a better understanding of their overall risk of heart disease and stroke, we can hopefully move more patients “off the fence” and onto the most appropriate treatment.
Stay tuned to find out what The Skeptical Cardiologist Recommended for Geo.
If you’d like to read the recently published recommendations of the US Preventive Services Task Force on statins for primary prevention of cardiovascular disease see here. Importantly this panel of unbiased experts concluded that statin therapy significantly reduced overall mortality and cardiovascular mortality. In addition, the review found no increased risk of diabetes overall with statin therapy. The only trial that identified an increased risk was using high intensity statin therapy (Crestor (rosuvastatin) >20 mg).
And, since the internet is jammed with people who believe statins robbed them of their brain power, I would advise noting that the writers concluded “These findings are consistent with those from a recent systematic review of randomized trials and observational studies that found no adverse associations of statins with incidence of Alzheimer disease, dementia, or decreased scores on tests of cognitive performance.”
One of the amazing perquisites of being a doctor is the opportunity to talk to a wide diversity of individuals with fascinating backgrounds and interests. I’ve always had some appreciation of this during my office interactions, but with age and ripening, I have come to relish and savor these conversations.
The skeptical cardiologist learns something from virtually every patient visit. On a recent office day, I received patient pearls on topics ranging from Viking River cruises in Germany, to the method by which Express Scripts squeezes money from Walgreens and drug manufacturers, to certain novels of T. Coraghessan Boyle not centered on the maniacal vegetarian John Harvey Kellogg.
Not uncommonly, I’ll learn something about medicine or cardiology if I listen closely to my patients and keep an open mind.
I saw a 69 year old woman (we’ll call her Donna) the other day who had advanced plaque in her coronary arteries and with whom I had initiated a discussion on the pros and cons of taking a statin drug to lower her risk of heart attack and stroke. This was not the first time we had talked about this topic; in previous visits she had shared with me her great fear of statin side effects and her desire to modify risk by dietary modification. On this visit, she came prepared with more research she had done on statins, and told me she was concerned about an increased risk of diabetes with statin drugs.
I gave her my standard spiel: statins, especially more potent ones like rosuvastatin and atorvastatin, appear to increase the risk of diabetes by 10-20%, however, this is offset by the benefits of statins, especially in someone with significant atherosclerosis, in reducing heart attack and stroke.
Donna then told me that she had read that pravastatin lowers the risk of diabetes. I hadn’t heard this (or more likely this slipped out of my ever-shrinking cerebral database) previously. Ten years ago, in the era before routine use of electronic health records (EHR), I would have had to just admit my ignorance and promise to look into that claim later (something that would not consistently happen due to time constraints and forgetfulness). However, now I enter the patient exam room with my MacBook Air, primarily to access the patient’s EHR and look at old notes, cardiac tests etc.
Increasingly I also use the Mac to quickly look up information about a topic the patient has brought to my attention – either double checking what I believe to be true or researching claims I am unfamiliar with.
Often, the topic raised is the “snake oil du jour” (for example, is turmeric a cardiovascular panacea?), but in this case and many others, it is a relevant question about the nuances of disease or my proposed treatment.
A quick search (20 seconds) pulled up a 2009 meta-analysis of randomized trials of statins and the risk of diabetes. Sure enough, one of these trials (the West of Scotland Coronary Prevention Study) actually showed that patients treated with 40 mg of pravastatin had a 30% lower risk of developing diabetes. Four studies showed no effect of statins on risk of developing diabetes and only one, the JUPITER trial utilizing rosuvastatin (Crestor), showed a slight increase.
For some patients like Donna, a higher risk of diabetes may be a deal breaker for taking a life-saving medication. Although I can confidently tell her that the benefits outweigh the risks, if she has a specific fear of diabetes, perhaps related to a family member who had horrific complications of the disease, she could easily decline to take statins.
In Donna’s case, this new information about pravastatin, confirmed by the wonders of Google and a fast WiFi connection led to her giving statins (in the form of pravastatin) a chance.
I’ll remember this patient-triggered drop of wisdom for future discussions with patients whose grave fear of diabetes makes them balk at taking statins.
The skeptical cardiologist stopped writing new prescriptions for niacin extended release tablets in 2011. For any patient who was taking niacin, I recommended stopping it.
Because niacin had favorable effects on the cholesterol profile, physicians had been utilizing it for many years in high risk patients on statins who had low HDL (good cholesterol) and/or high triglycerides.
The rationale was that, since high HDL was associated with lower risk of heart attacks, raising the HDL would lower that risk. Similarly, lowering the triglycerides would improve cardiovascular risks.
While niacin certainly improved the cholesterol profile, there was no good evidence that starting it in a patient already on statin would improve cardiovascular outcomes. The cholesterol profile is a surrogate endpoint: the actual treatment goal is reducing cardiovascular disease.
In 2011, the AIM-HIGH study proved there was no benefit to adding niacin to good statin therapy despite increasing HDL from 35 to 42 mg/dl, lowering triglycerides and lowering LDL. This and other studies showing no benefit of niacin therapy (and worrisome adverse effects) should have resulted in the total cessation of niacin prescriptions, especially in patients on statins.
Unfortunately, old habits die hard amongst physicians, and the allure of raising HDL and lowering triglycerides with niacin persisted despite a lack of evidence of any benefit in lowering cardiovacular risk.
Yesterday, the FDA announced it was removing from the market two drugs made by Abbvie, Advicor and Simcor, which are combinations of extended release niacin plus lovastatin or simvastatin, and removed its approved indication for niacin ER plus statin for lowering CHD risk stating:
“Based on the collective evidence from several large cardiovascular outcome trials (Refs. 1-3), the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events. Consistent with this conclusion, FDA has determined that the benefits of niacin ER tablets and fenofibric acid DR capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn.”
This is good news for patients whose physicians were keeping them on the unproven brand name combination drugs, Advicor and Simcor.
There are still legitimate uses of niacin to prevent vitamin deficiencies but If you are still taking some form of niacin ER for the purpose of preventing heart disease with or without a statin I recommend presenting your doctor with the link to the FDA pronouncement above and having a good discussion with him about the rationale for staying on it.
The other drug mentioned in the announcement, fenofibric acid, is far less often prescribed and is not available as a combination. It is the most effective drug we have for extremely high triglyceride levels over 500 mg/dl which can cause pancreatitis. I have a few patients on the generic fenofibric acid strictly for the purpose of lowering their dangerously high triglycerides but not for the indication of lowering their cardiovascular risk.
No, you are not “sabotaging” your heart with statin drugs. Neither are you “wrecking” your heart.
But that title probably got your attention if you are taking a statin drug and thought that it was helping your heart.
This question is prominently displayed on the Health portion of a news website called Newsmax, that somehow interrupted my web surfing today. If you click on the banner, you will get to listen to the words of Dr. David Brownstein, “America’s most popular family physician.”
Dr. Brownstein, in my opinion, should more properly be termed “one of America’s most popular quacks, charlatans and purveyors of misinformation in order to market useless junk.”
What Brownstein says can be found on multiple similar sites across the internet which are promoting “alternative” or “natural” approaches to high cholesterol.
His claims can be summarized as follows:
statin drugs do nothing to protect you from heart attacks
statin drugs “weaken your heart,” muscles, cause fatigue and lower your sex drive, damage your kidneys and liver
statin drugs prevent the formation of cholesterol which is essential for brain, sex hormone and vitamin D production
1/2 of people with heart attacks have normal cholesterol levels
CHF is increasing in frequency and it is related to an increase in statins and consumption of sugar and refined carbohydrates
Big pharma has perpetrated the biggest fraud in medical history on the American public by brainwashing doctors, beginning in medical school, to prescribe statin drugs
These claims resonate with patients who are reluctant to take medications and who feel that “natural” approaches to prevention and treatment are superior.
Brownstein uses a combination of alarmist rhetoric and pseudoscientific jargon that appeals to those seeking alternatives.
Let’s look at his claims.
Do Statins Prevent heart Attacks?
Statins unequivocally prevent heart attacks in patients who have had heart attacks or have evidence of advanced vascular disease due to atherosclerosis. This is called secondary prevention and there are almost no cardiologists/scientists with any credibility who dispute the value of statins in secondary prevention.
The only specific study that Brownstein cites is the ASCOT-LLA study, published in 2003 which looked at ten thousand patients with hypertension, no heart disease and low or normal cholesterol levels, half of whom got 10 mg of atorvastatin and half a placebo.
This was a primary prevention study and showed such a benefit of the atorvastatin on reducing heart attack and coronary deaths that the study was stopped early, at 3.3 years at which time 154 patients receiving placebo versus 100 receiving atorvastatin had had heart attacks or died from coronary disease.
This was a highly significant reduction in events. There are several ways to look at this data and present it to patients; Brownstein implies that “Big pharma” presented the most favorable way, which is that there was a 36% reduction in relative risk.
The absolute risk of an event in the atorvastatin group was 1.7% (2.7% in the placebo group), so the absolute risk reduction was from 2.7% down to 1.7% or 1%.
To help better understand the data, we can also look at the number needed to treat (NNT). The NNT is the inverse of the absolute risk reduction. So for the ASCOT trial, the absolute risk reduction was 1%. 1 divided by 1% is 100 — 100 people would need to be treated with atorvastatin (the generic of Lipitor) over the study period to prevent one heart attack. (For more discussion on the NNT check out this blog post and this paper on its limitations)
Understandably, Pfizer, the makers of atorvastatin, prominently displayed the 36% relative risk reduction in their direct to consumer marketing campaigns (featuring Dr.Robert Jarvik (proclaiming himself a doctor in direct to consumer videos), although he was never a licensed physician (see here for interesting discussion on the controversy that ensued)).
Until, the FDA compels them to do otherwise, big pharma will project their products in the most favorable light possible.
However, it is debatable whether presenting data to patients using absolute risk reductions or NNT info plus relative risk reductions results in better choices. As Mcalister has pointed out:
“For example, many British patients with atrial fibrillation who were likely to benefit from anticoagulant therapy because of their risk profiles and their similarity to the participants in randomized trials supporting the efficacy of warfarin declined warfarin therapy when presented with the data about their absolute risks and benefits.”
ASCOT really makes a strong case for taking a statin drug to prevent heart attacks, even in those with normal or low cholesterol levels, not the opposite, as Brownstein has implied.
Do Statin Drugs “Weaken” The Heart Muscle Or Cause Heart Failure?
After criticizing the now infamous “Seven Nations Study” of Ancel Keys, which found high fat consumption in countries with high rates of heart attacks, Brownstein trots out the weakest imaginable argument for statins causing heart failure: heart failure has increased in the last decades, statin use has increased, therefore statins are causing heart failure.
Correlation does not equal causation!
There is no compelling evidence that statins cause heart failure or weaken heart muscle.
In fact, a recent review of heart failure and statins concluded that statins, while not reducing mortality in heart failure, do have favorable effects on reducing the rate of hospitalization for heart failure and increasing the strength of the heart muscle.
Statins may not be as beneficial in patients with heart failure, but they definitely don’t cause heart failure.
Much of the misinformation about heart failure and statins arises from sites like Life Extension, which promotes sales of its own preferred brand of vitamin CoQ10, ubiquinol. (According to their website, though, this is for altruistic reasons: “We at the Life Extension Foundation take a different view. Keeping our members in a youthful state of longevity is the most efficient way of maintaining the revenue stream we need to fund our scientific research projects. We had no problem reducing our margins to provide members with the clearly superior ubiquinol form of CoQ10.”)
As is typical for this slick organization (see my previous post here), the writing has the veneer of science but is all pseudoscience with references that are outdated, irrelevant or meaningless.
Statin Side Effects
I’ve written about statin side effects and the decision to take them based on analysis of risks and benefits here and here.
By far, the most common thing we see is myalgia, aching of the muscles, and this is reversible.
The bottom line is that the benefits of statins far outweigh the risks if you are at very high risk for heart attack and stroke. The risks outweigh the benefits if you are at very low risk.
Brownstone is not the only purveyor of dangerous misinformation on Newsmax’s Health website. There seems to be a concerted effort to promote quacks and charlatans and any information on this website is suspect.
A good rule of thumb if you are searching for credible health information on the web:
Avoid sites that use scare tactics and inflammatory rhetoric to induce you to stop your prescription medication and buy a health newsletter or nutraceutical.
By the way, Big Pharma has not brainwashed me.
I have no ties to industry.
I stopped taking any pharma food or money years ago.
Yes. PCSK9 is a factor in escalating LDL cholesterol levels. The point was brought home as I rode the escalator up from the first to the top floor of the San Diego Convention Center at this year’s American College of Cardiology meetings. I suspsect if I had taken an elevator I would have seen a sign proclaming that PCSK9 is a factor in elevating cholesterol levels.
And PCSK9 signage is everywhere in this meeting.
Proprotein convertase subtilisin/kexin type 9, also known as PCSK9, is an enzyme that appears to degrade LDL receptors.
If you are born with a mutation that produces less active PCSK9 you have more LDL receptors and consequently more LDL is taken out of circulation leading to lower LDL levels.
Mutations leading to gain of PCSK9 function result in lower LDL receptors, higher LDL levels and substantial clinical evidence for premature atherosclerosis.
Amgen has produced all the PCSK9 signs that abound at the ACC meetings because they have produced a fully humanized monoclonal antibody (utilizing Chinese hamster ovaries) that inhibits PCSK9 and does a great job of lowering LDL without significant adverse effects.
At a late-breaking clinical trial session, results of longer term follow up of the company’s Osler randomized trials were presented and simultaneously published here.
The results were remarkably good. Not only did evolocumab drop LDL by 61% (from 120 down to 48) it showed significant improvement in cardiovascular outcomes.
“The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).”
According to the biotech website fiercebiotech:
“The antibody is expected to win FDA approval by Aug. 27, trailing Sanofi ($SNY) and Regeneron’s ($REGN) alirocumab, which, thanks to some regulatory opportunism, is likely to hit the market a month or so before. Pfizer ($PFE) is in third place, working through Phase III with its bococizumab. Analysts say each treatment could bring in more than $3 billion a year at its peak…”
More study is needed of these drugs before approval in my opinion for a number of reasons. There is evidence of a small, but significant increase in neurocognitive side effects for one.
Although with evolocumab these were not related to the level of LDL achieved, there are concerns that extremely low LDL levels may interfere with neural development and such effects may not manifest for years.
The study authors did a good job of pointing out other limitations including small number of events, open-label design and patients selected who were free of adverse events. Hopefully, the FOURIER study will resolve these issues.
This post was also posted at SERMO, the physician social network. I would encourage physicians to join in the robust discussions on medicine and other topics at this site.