Category Archives: Statin Drug Therapy

Are You Taking A Statin Drug Inappropriately Like Eric Topol Because of the MyGeneRank App?

The skeptical cardiologist was listening to a podcast discussion between Sam Harris and Eric Topol recently and became  flabbergasted.

Topol, the “world-renowned cardiologist” who is seemingly everywhere in media these days was discussing what he considers the overuse of imaging technology during the podcast which Harris’s website describes as follows:

In this episode of the Making Sense podcast, Sam Harris speaks with Eric Topol about the way artificial intelligence can improve medicine. They talk about soaring medical costs and declining health outcomes in the U.S., the problems of too little and too much medicine, the culture of medicine, the travesty of electronic health records, the current status of AI in medicine, the promise of further breakthroughs, possible downsides of relying on AI in medicine, and other topics.

Personally, I have been amazed at the hype and promotion that artificial intelligence (AI) has been getting given the near total absence in cardiology of any tangible benefits from it and I wanted to hear what the man who wrote ” Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again ” had to say about it.

About 28 minutes into the podcast, Harris, who has lately been preoccupied with promoting meditation as a cure for all ills, begins describing a procedure he underwent:

I’ve had a few adventures in cardiology. CT scan, calcium score scan.

Harris, who in neuroscience and philosophy might speak precisely, here is very vague. Did he get a coronary calcium scan (CAC) or a coronary CT angiogram? There is a huge difference and he is conflating the two imaging procedures.

Apparently he is unhappy with having undergone it but:

I might be telling a different story if my life was saved by it.

And his doctor’s rationale  for getting the scan was lacking:

The way this was dispensed to me. We now have this new tool, let’s use it.

Let me just say at this point that if your doctor’s rationale for performing a test is that he has a machine that performs the test just say no. Or demand an explanation of how the results will change your management or prognosis.

Apparently the scan that Harris had didn’t turn out either horrifically worse than expected or remarkably better and didn’t change management:

In my case at the end it didn’t make sense.

Now, I can forgive Sam Harris for being somewhat naive and misguided when it comes to coronary artery scans or coronary CT angiograms but Eric Topol , the world’s leading talking cardiology head should fully understand the value of coronary artery calcium scans.

This is where I first become flabbergasted.

Topol says in response at this point that coronary artery calcium scans are “terribly overused” and that “I’ve never ordered one.”

Eric, you cannot be serious!

Are you telling me that you wouldn’t order one on your 60 year old airline pilot friend whose father dropped dead of a massive MI at age 50 but whose lipids look fine?

Why doesn’t Eric order CACs?

Because “There are so many patients who have been disabled by the results of their calcium score even though they have no symptoms.”

This is where the degree of my flabbergastment increased by an order of magnitude.

Our job as preventive cardiologists is to identify those at high risk and lead them to lifestyle choices and medicine that dramatically lowers that risk.  We educate them that the large build up of subclinical atherosclerosis we identified does not have to result in sudden death, crippling heart attacks or strokes. We reassure them that with the right tools we can help them live a long, productive and happy life.

Eric, what do you tell these people? The calcium score is irrelevant? You’re fine. You shouldn’t have gotten it. Surely not! This would be the preventive cardiology equivalent of sticking one’s head in the sand.

This is not the first time Topol has opined on the dangers of CAC. An excerpt from his book, ‘The Patient Will See You Now: The Future of Medicine Is in Your Hands” posted on Scientific American describes the ills created in a 58 year old man who had a CAC score of 710.

My patient was told that he had a score of 710—a high calcium score—and his physician had told him that he would need to undergo a coronary angiogram, a roadmap movie of the coronary anatomy, as soon as possible. He did that and was found to have several blockages in two of the three arteries serving his heart. His cardiologists in Florida immediately put in five stents (even though no stress-test or other symptoms had suggested they were necessary), and put him on a regimen of Lipitor, a beta-blocker, aspirin and Plavix.

This case is not an example of inappropriate usage of CAC it is an example of really bad doctoring and failure to utilize the CAC information properly.

One should never order a cardiac catheterization/coronary angiogram solely on the basis of a high CAC score. Even ordering a stress test in this situation is debatable as I discuss here.

And Topol’s patients symptoms were most likely related to a beta-blocker that he didn’t need (see here).

My Gene Rank

Later in the podcast I reached maximum flabbergast  levels when Topol announced that as a result of a high score for CAD risk he received using an iPhone app called MyGeneRank he had started taking a statin drug.

He enthusiastically promoted the app which his Scripps Translational Science Institute developed and urged listeners to utilize this approach to better refine the estimate of their risk of heart attack and stroke.

Per the Scripps website:

The MyGeneRank mobile app is built using Apple’s ResearchKit, an open source framework that enables researchers and programmers to build customized mobile apps for research purposes. With user permission, the app connects with the 23andMe application program interface and automatically calculates and returns a genetic risk score for coronary artery disease.

In addition, the app calculates a 10-year absolute risk estimate for an adverse coronary event, such as heart attack, using a combination of genetic and clinical factors. Users are able to adjust behavioral risk factors to see the influence of lifestyle habits on their overall risk.

Elsewhere, Topol, has stated

“We are excited to launch a unique study that combines an iOS app and genomics to help guide important health decisions,” says Eric Topol, MD, Founder and Director of the Scripps Translational Science Institute and Professor of Molecular Medicine at The Scripps Research Institute. “Not only does participating in the study arm individuals with their own data, but it also gives them the opportunity to participate in new type of research – one that is driven by and for patients.”

Curious, I downloaded the MyGeneRank app, answered some questions and gave it permission to access my 23 and Me data. After requiring me to complete a survey on my health it then  yielded  my coronary artery disease risk score.

 

 

 

 

 

 

 

Oh, no! My genetic risk score was at the 81st percentile! In the red zone.  According to Eric Topol I should take a statin like him. Based on these results I probably should be incredibly anxious and crippled by fears of cardiac death.

Fortunately, I have superior information to allay my fears. I’ve had CAC scans in the past which are well below average for men my age. Despite my dad’s history of early CAD, a recent coronary CT angiogram showed minimal plaque. I know exactly where I stand risk-wise.

How many cardiac cripples has Topol’s MyGeneRank inappropriately created?

Is the data that MyGeneRank utilizes superior to that from CAC scans?

For coronary artery calcium scanning there is a wealth of data supporting improved risk prediction and we are looking directly at the atherosclerotic process that eventually causes the diseases we want to prevent.

It’s interesting that a recent study looking at a polygenetic risk score’s ability to predict cardiac events was comparing the risk score’s ability to predict subclinital atherosclerosis:

Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque.

In the Scientific American article Topol quotes Mark Twain:, “To a man with a hammer, a lot of things looks like nails that need pounding.”

Topol’s hammer is artificial intelligence. We eagerly await the day he discovers a nail that he can bang on that  significantly advances medical care.

In the meantime I and the vast majority of progressive preventive cardiologists will be utilizing CAC scores intelligently to identify both those patients at high risk for cardiovascular events who need more aggressive treatment and those at low risk who can be reassured and have treatment de-escalated.

Polygenetic CAD risk scores do show promise to improve our predictive powers but more study is needed in this are before we make clinical treatment decisions based on the results.

Astoundingly Yours,

-ACP

Ilene Has High Cholesterol With A “Wonderful Ratio” And A Branch Retinal Vein Occlusion: Should She Take A Statin?

Recently the skeptical cardiologist was asked by Ilene, a reader with an HDL almost as high as her LDL and a history of branch retinal vein occlusion (BRVO) whether she should take the statin her cardiologist had prescribed.

I enjoy reading your articles and would appreciate your opinion on my situation.  I recently took a lipid panel blood test: total cholesterol: 244 HDL:112 LDL:121 VLDL:11  CRP: 1.77 Triglycerides: 57.  Also my Cardiac Agatston  score is 21.
I had a Branch Retinol Vein Occlusion a year ago in my left eye  (it’s healing beautifully) and as a precaution  am now taking Amlodipine 5mg daily (my blood pressure was never too high to begin with) along with a daily baby aspirin.
I am otherwise a healthy 72 year old woman, exercise and eat healthy.
My regular doctor (Integrative MD) says my cholesterol ratio is wonderful….my cardiologist wants me to take a statin (Atorvastatin) in a low dose.  The ONLY med I take is Amlodipine and I am not one to be taking a plethora of meds for the rest of my life (unless “absolutely” necessary.  What is your suggestion…take a statin or not.
While I can’t provide medical advice to Ilene specifically it is worthwhile  to ponder  the general aspects of her case and how I would approach it as it likely applies to thousands of other patients including many of my own.
In my mind there are two questions here: 1) Should Ilene and patients like her take a statin to prevent future heart attacks and strokes and 2) Do statins  effect the Branch Retinal Vein Occlusion (BRVO)?
Although I’m not a fan of integrative or functional medicine Ilene’s integrative MD is correct in saying that her ratio of total cholesterol to HDL cholesterol is wonderful. Perhaps that high  HDL is protecting her from a build-up of atherosclerotic plaque.
On the other hand, Ilene tells me that  “My father did have a heart attack in his 60’s”.  Perhaps she inherited something from him that puts her in a higher than average risk category.
With the information from the CAC we don’t have to guess about the influence of the high HDL and the family history of CAD. Her score is at the 48th percentile, slightly below average for white women her age, thus it would appear she is not destined for her father’s fate.
Frequent readers of skepcard (especially my posts on statin fence sitters) will know I  plug all these numbers (preferably with the calcium score available) into the MESA coronary calcium risk calculator
In this case, the CAC score does not significantly alter our risk estimate as it is so close to the average for her age
Even if we count her as having hypertension because she is on the amlodipine her 10 year risk of heart attack and stroke is low at 3.2%.
Guidelines don’t recommend statin treatment unless risk is >7.5%.
Also, note that I answered yes to “Family history heart disease” but most studies generally only consider this a risk factor if father had heart attack prior to age 55 years. If we make that a no the risk drops to <3%.
Now that we’ve answered Ilene’s real question let’s see if the BRVO warrants statin therapy.
Branch Retinal Vein Occlusion
BRVO is the blockage of a vein from the retina and the second most
common cause of vision loss from retinal vascular disease, following diabetic retinopathy. It typically  results in the painless loss of vision in one portion of one eye due to hemorrhage and edema in the retina.
A reasonable summary of BRVO provided by the American Academy of Ophthalmology can be found here.
BRVO is not clearly related to atherosclerosis or hyperlipidemia and there is no evidence that taking a statin would prevent recurrence or help the condition.

The leading theory for what causes BRVO is that the more delicate and distensible retinal veins are squished or compressed at points where the stiffer and thicker retinal arteries cross them.  Up to Date notes:

Whereas branch retinal vein occlusion (BRVO) appears to be related to compression of the branch vein by retinal arterioles at the arteriovenous crossing points, central retinal vein occlusion (CRVO) is usually associated with primary thrombus formation.

Although BRVO is more common in patients with hypertension and atherosclerosis it is not clear that one causes the other or that treatment of hypertension or atherosclerosis diminishes the risk of BRVO.  So statins are not recommended.
More Questions
Every patient case for me leads to more questions,  more investigations and more knowledge. Here are some questions that occurred to me from ilene’s case.
-Why would someone with no symptoms and no heart problems be seeing a cardiologist?
(“I started seeing a cardiologist just to make sure all systems were “go” and stayed that way!… we take care of our cars so why not my body. )
I kind of like this answer and I definitely see lots of patients with that philosophy but if we extrapolate the car analogy: going to a cardiologist would be like taking your car to a mechanic who only works on engines or perhaps one specific part of the engine (help me out here people who know about cars.)
-Why was Ilene unwilling to take a statin? (I pretty much know the answer to this (see here) for most patients.
‘m just afraid of the horrible muscle related side effects of statin drugs…and that’s why I’m taking Berberine 500mg twice a day.
Yep. I feel a post abut Berberine may be in the works!
-Finally, should a 72 year old with a CAC score of 21 and BRVO be taking a baby aspirin?
I’ve generally advocated aspirin in primary prevention for scores >100  so wouldn’t advise it for prevention of cardiovascular events in this situation.
In addition, I have seen nothing in the literature that recommends aspirin for BRVO. These two BRVO experts do not recommend either aspirin or anticoagulants.
Proretinally Yours,
-ACP
N.B. If you have a blockage of the the artery that supplies blood to the retina or a branch retinal artery occlusion ( BRAO)
you might benefit from a statin as this is often caused by a clot or plaque flying out of the heart or the carotid artery.

The Ultimate Guide To The Coronary Artery Calcium Scan (Score) Circa 2019

The skeptical cardiologist’s first post on coronary artery calcium (CAC) scan was posted in 2014 and had the wordy title “Searching for Subclinical Atherosclerosis: Coronary Calcium Score-How Old Is My Heart?”

This post still serves as a good introduction to the test (rationale, procedure, risks) but in the 5 years since it was published there has been a substantial body of data published on CAC and in 2018 it was embraced by major organizations.

Overall, I’ve written 20 posts in which CAC plays a predominant role since then and I feels it’s time to put the most important changes and concepts  in one spot.


Detection Of Subclinical Atherosclerosis: What’s Your Risk of Dropping Dead?

First, the rationale for using CAC (also known as a coronary calcium score or heart scan) is detection of “subclinical atherosclerosis”, a non-catchy but hugely important process which I describe in an early post on who should take aspirin to prevent heart attack or stroke:

We have the tools available to look for atherosclerotic plaques before they rupture and cause heart attacks or stroke. Ultrasound screening of the carotid artery, as I discussed here, is one such tool: vascular screening is an accurate, harmless and painless way to assess for subclinical atherosclerosis.

In my practice, the answer to the question of who should or should not take aspirin is based on whether my patient has or does not have significant atherosclerosis. If they have had a clinical event due to atherosclerotic cardiovascular disease (stroke, heart attack, coronary stent, coronary bypass surgery, documented blocked arteries to the legs) I recommend they take one 81 milligram (baby) uncoated aspirin daily. If they have not had a clinical event but I have documented by either

  • vascular screening (significant carotid plaque)
  • coronary calcium score (high score (cut-off is debatable, more on this in a subsequent post)
  • Incidentally discovered plaque in the aorta or peripheral arteries (found by CT or ultrasound done for other reasons)

then I recommend a daily baby aspirin (assuming no high risk of bleeding).


Help In Deciding Who Needs Aggressive Treatment

Second, CAC is an outstanding tool for further refining risk of heart attack and stroke and helping better determine who needs to take statins or undergo aggressive lifestyle reduction, something I described in detail in my post “Should All Men Over Sixty Take a Statin Drug”.

The updated AHA/ACC Cardiovascular Prevention Guidelines came out in 2013.

After working with them for 9 months and using the iPhone app to calculate my patients’ 10 year risk of atherosclerotic cardiovascular disease (ASCVD, primarily heart attacks and strokes) it has become clear to me that the new guidelines will recommend statin therapy to almost all males over the age of 60 and females over the age of 70.

As critics have pointed out, this immediately adds about 10 million individuals to the 40 million or so who are currently taking statins.

By identifying subclinical atherosclerosis, CAC scoring identifies those who do or don’t need statins.


This is particularly important for patients who have many reservations about statins or who are “on the fence” about taking them when standard risk factor calculations suggest they would benefit.


The Widowmaker

In 2015 I wrote about a documentary entitled “The Widowmaker” (see here and here) which is about the treatment and prevention  of coronary artery disease and what we can do about the large number of people who drop dead from heart attacks, some 4 million in the last 30 years:

The documentary, as all medical documentaries tend to do, simplifies, dumbs down and hyperbolizes a very important medical condition. Despite that it makes some really important points and I’m going to recommend it to all my patients.

At the very least it gets people thinking about their risk of dying from heart disease which remains the #1 killer of men and women in the United States.

Perhaps it will have more patients question the value of stents outside the setting of an acute heart attack. This is a good thing.

Perhaps it will stimulate individuals to be more proactive about their risk of heart attack. This is a good thing.

Although CAC has some similarities to mammography (both utilize low dose radiation, 0.5 mSV) I concluded that CAC was not “the mammography of the heart” as the documentary proclaims.

What We Can Learn From Donald Trump’s CAC?

In 2018 I noted that “Donald Trump Has Moderate Coronary Plaque: This Is Normal For His Age And We Already Knew It.”

In October, 2016 the skeptical cardiologist predicted that Donald Trump’s coronary calcium score, if remeasured, would be >100 .  At that time I pointed out that this score is consistent with moderate coronary plaque build up and implies a moderate risk of heart attack and stroke.

Trumps’ score gave him a seven-fold increase risk of a cardiovascular event in comparison to Hilary Clinton (who had a zero coronary calcium score) .

Yesterday it was revealed by the White House doctor , Ronny Jackson, that Trump’s repeat score  was 133.

I was able to predict this score because we knew that Trump’s coronary calcium was 98 in 2013 and that on average calcium scores increase by about 10% per year.

What is most notable about the Trump CAC incident is that Trump, like all recent presidents and all astronauts underwent the screening. If the test is routine for presidents why is it not routine for Mr and Mrs Joe Q Public?

At a mininum we should consider what is recommended for aircrew to the general public:

A three-phased approach to coronary artery disease (CAD) risk assessment is recommended, beginning with initial risk-stratification using a population-appropriate risk calculator and resting ECG. For aircrew identified as being at increased risk, enhanced screening is recommended by means of Coronary Artery Calcium Score alone or combined with a CT coronary angiography investigation.

The 2018 guidelines Take A Giant Step Forward

In late 2018 I noted that CAC had been embraced by major guidelines:

I was 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.

A Few Final Points On CAC

First, it’s never too early to start thinking about your risk of cardiovascular disease. I have been using CAC more frequently in the last few years in  individuals <40 years with a strong family of early sudden death or heart attack and often we find very abnormal values (see here for my discussion on CAC in the youngish.)

coronary calcium scan with post-processing on a 45 year old white male with very strong history of premature heart attacks in mother and father. The pink indicates the bony structures of the spine (bottom) and the sternum (top). Extensive calcium in the LAD coronary artery is highlighted in yellow and in the circumflex coronary artery in ?teal. His score was 201, higher than 99% of white male his age.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.

Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.

Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.

The Importance of Proactivity

In “The MESA App-Estimating Your Risk of Cardiovascular Disease With And Without Coronary Calcium Score” I recently wrote that:

If you want to be proactive about the cardiovascular health of yourself or a loved one, download the MESA app and evaluate your risk.  Ask your doctor if a CACS will help refine that risk further.

There are many other questions to answer with regard to CAC-should they be repeated?, how do statins influence the score?, is there information in the scan beyond just the score that is important? Is a scan helpful after a normal stress test?

I’ve touched on some of these in the past, including the really tough  question “Should All Patients With A High Coronary Calcium Score Undergo Stress Testing?

Like most things in cardiology we have a lot to learn about CAC. There are many more studies to perform. Many questions yet to be answered.

A study showing improved outcomes using CAC guided therapy versus non CAC guided therapy would be nice. However, due to the long time and thousands of patients necessary it is unlikely we will have results within a decade.

I don’t want to wait a decade to start aggressively identifying who of my patients is at high risk for sudden death. You only get one chance to stop a death.

Apothanasically Yours,

-ACP


 

Is Pitavastatin (Livalo) A Better Statin For You?

The skeptical cardiologist recognizes that perhaps 10% of patients he starts on a statin drug will develop symptoms that are felt to be due to the drug.

Most often the symptom is myalgia-muscle ache.

But other symptoms may develop after the patient starts the drug and given widespread statin fear-mongering on the internet it is common for these symptoms to be attributed to the statin.

Recently a reader left comments on my post on statins and memory problems describing in detail what appears to be a statin side effect:

My doctor had me on a daily 40mg Lipitor. After about 1 month, I noticed that my short term memory was very bad*. (Not a nocebo effect… I had no idea at the time that statins were linked to memory effects.) I did an experiment on myself. I suspected that my memory problems were the result of the statin. (Nothing else seemed to be different besides the fact that I had started taking Lipitor the previous month.) After 2 weeks off of Lipitor, my memory problems went away. Whew. I put myself back on Lipitor (I didn’t want to die of a heart attack, and my “experiment” could have been a victim of confirmation bias + 100 other faults.) After about a month, crappy short term memory returned. Took myself off Lipitor again. AGAIN, after about 2 weeks, by memory was fine again.
Perhaps my experiment wasn’t scientific. Just one subject (me). 100% anecdotal. Perhaps statins are good for your heart. However, I don’t know about you, but I program computers for a living. Try doing that with crappy short term memory. Hint: you can’t do it.

I’ve outlined my approach to these potential statin associated symptoms (PSAS) previously (see here) and if a patient has resolution of the PSAS we typically try another statin to see if the PSAS recurs.

For my reader, it would make sense to try a statin like rosuvastatin or pitavastatin that is hydrophilic and therefore doesn’t cross the blood-brain barrier and enter the brain.

For the more common myalgias I typically try rosuvastatin at lower dosage. If symptoms recur on rosuvastatin I try pitavastatin.

Pitavastatin (Livalo)

Pitavastatin (Livalo) is the seventh statin. It is minimally affected by the cytochrome P450 system (meaning less drug-drug interactions),  water soluble (so it doesn’t enter the brain,) and does not lower Co-enzyme Q10.  These special biochemical characteristics raise the possibility that  among patients who have not been able to tolerate other statins it might be both usable and efficacious.

It has been used in Japan since 2003 and was approved by the FDA for US use in 2010. The Medical Letter was pretty negative about it in 2010 and feels the same way about the recently approved zypitamag (pitavastatin magnesium.)

The Medical Letter’s review of pitavastatin calcium concluded that recommended doses of the drug had not been shown to decrease LDL-C more than other statins with longer safety records and there was no good reason to use it. That conclusion applies to pitavastatin magnesium as well.

Tom Dayspring, the “national treasure” and lipidologist disputes this and has written of the Medical Letter conclusions

Any statin that has been tested in an outcome trial has been successful and there is no reason why pitavastatin would not also reduce events. Most providers used every statin for years before there were outcomes! Pitavastatin was as successful in
regressing plaque volume as was atorvastatin in an IVUS trial called JAPAN-ACS ((J Am Coll Cardiol 2009;54:293–302). The claim regarding LDL lowering is erroneous as pitavastatin is actually more efficacious than fluvastatin, pravastatin, lovastatin, and 10 & 20 mg doses of simvastatin and the last sentence in the Medical Letter using the word “worrisome” is both ridiculous and 100% false – The pharmacokinetics of pitavastatin are extremely clean, better than all of the more lipophilic statins now on the market except fluvastatin (read the reference cited above which compares pitavastatin to all other statins using published data not invective). I cannot remember the last branded drug that was not first in its class to be released that the Medical Letter found any use for including Crestor which is why personally I find little use whatsoever for recommendations of the medical letter.

The Medical Letter does provide a nice summary of statins effectiveness and cost. As you can see Livalo (and any brand name statin) costs a lot more than generic rosuvastatin (276$ versus 8$) and is less effective

statins.png

 

Thus, there is no reason to use any brand name statin unless you have developed side effects on two generic statins with the second one being low dose rosuvastatin.

Anecdotal Pitavastatin Success

Four years ago I identified by vascular screening in one of my patients, a 65 year old woman a >50% blockage in the left  carotid artery.

We started her on 40 mg atorvastatin and she developed a rash. She was switched to rosuvastatin 10 mg and began waking up in the middle of the night with a headache and feeling light-headed. I thought it unlikely this symptom was due to the statin.

She requested that we go back to atorvastatin because she felt it likely the rash was from something else.one month later, complains of arms and legs are very sore and hard time getting dressed in the morning due to soreness. also constipated

We stopped the atorvastatin and a month later she called back indicating that she could feel her arteries clogging.

At this time we started Livalo at 2 mg twice weekly. LDL dropped by 50% to 71 mg/dl and she has tolerated it without side effects ever since.

Supporting Data

Beyond anecdotal support for pitavastatin in the statin intolerant patient we have one abstract presented at the ACC meetings in 2013.

A total of 40 consecutive patients with documented intolerance to any dose of at least two different statins were prospectively enrolled into a protocol whereby they received a trial of pitavastatin therapy at a dose of 2 mg per day.

Forty patients were enrolled and 27 of them (68%) were able to tolerate pitavastatin. LDL cholesterol was reduced from 147±27 mg/dL to 93±25 mg/dL, resulting in an average LDL-cholesterol reduction of 34%. Patients who could best tolerate pitavastatin tended to be males and those with no history of coronary artery disease or diabetes.



Despite what the Medical Letter says about pitavastatin I tend to agree with Tom Dayspring and I and most progressive preventive cardiologists will give pitavastatin at least a trial in our high risk patients with PSAS before giving up on statins in them.


Hydrophilicly  Yours,

-ACP

N.B. Pitavastatin was discovered in Japan by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo. It has been extensively studied in Japanese studies.

The Livalo website tries to hint that their drug might be better/safer for those of Japanese ethnicity but the science on this is not clear. A review on the topic concludes

Pharmacokinetic investigations have noted higher plasma levels of statins in Asians compared with Caucasians, although postmarketing data for all statins have not identified any particular safety issues, even when statins are given at equivalent doses. The potential mechanisms of heightened response to statins in Asians are related to genetically based differences in the metabolism of statins at the level of hepatic enzymes and drug transporters. Studies indicate that lower statin doses achieve lipid improvements in Asian patients comparable with those observed with higher doses in Caucasians. In conclusion, prescribing lower starting doses of statins in Asians appears warranted while research on this subject continues.

Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish

Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.

How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.

We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.

Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.

Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.

I’ve been utilizing CAC (also termed  heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for

adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain

Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.

To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.

Significant Of CAC Score

As the new ACC/AHA guidelines state:

If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.

A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.

Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years

Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400

Patients without a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.

On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.

f2.large-3
Patients with CAC who were prescribed a statin had a significantly reduced risk of MACE (aSHR: 0.76; 95% CI: 0.60 to 0.95; p = 0.015), whereas patients without CAC had no associated MACE reduction (aSHR: 1.00; 95% CI: 0.79 to 1.27; p = 0.99). p = 0.097 for interaction between statin treatment and CAC presence. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s)

The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.

Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.

f3.large
Benefit of statin therapy was significantly related to CAC group with benefit in patients with CAC score >100 but not in patients with CAC <100. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s).

But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).

Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)

f2.large-4

 

Benefits of CAC Testing In The Young

So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.

But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.

The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events.  It was  a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.

The conclusions:

Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.

screen shot 2019-01-19 at 12.36.44 pmI read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.

The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them  10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.

Other Risk-Enhancing Factors To Consider In The Young

The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.

screen shot 2019-01-19 at 7.33.39 am

Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?

What about nontraditional lipid/biomarkers?  I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.

Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.

Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.

It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.

Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.

Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.

Skeptically Yours,

-ACP

Don’t Stop Taking Your Statin Cholesterol Drug Based On The Latest News Headline

In a previous post the skeptical cardiologist discussed his approach to a typical sixty-something male, Geo,  who was “on the fence” about taking the statin drug his PCP had recommended (see here.)

After acquiring more information on his level of subclinical atherosclerosis (coronary calcium and vascular screening), and discussing the risks and benefits of statins for primary prevention, I wrote about his experience in using my recommended “compromise approach.”

This approach utilizes a low dose of rosuvastatin taken intermittently with the goal of minimizing any statin side effects, but obtaining some of the benefits of statin drugs on cardiovascular risk reduction.

It worked well for Geo; taking 5 mg rosuvastatin three times weekly lowered his LDL-C (bad cholesterol) by 50%, and he had absolutely no side effects when I reported on him 6 months after starting the drug.

However, when I stayed with Geo and his lovely wife, Wendy, over Thanksgiving in their Annapolis, Maryland house, Geo revealed that he had stopped taking his statin.

Like many patients, he was swayed by a news report suggesting an important “new study” that suggested there was no relationship between cholesterol and heart disease, and that statin drugs were dangerous and should be stopped.

At first I thought the story that he had read was the one I reported here which (appropriately) questions the benefit of statins for primary prevention in patients over the age of 75.

However, after a bit of searching, Geo told me the article that caused him to stop taking his statin was a UK Daily Mail one entitled:

‘No evidence’ having high levels of bad cholesterol causes heart disease, claim 17 physicians as they call on doctors to ‘abandon’ statins

The Daily Mail article says at one point

But the new study, based on data of around 1.3 million patients, suggests doling out statins as a main form of treatment for heart disease is of ‘doubtful benefit’.

Is this really a “new study” that contradicts the great body of evidence showing that statin treatment is safe and effective in preventing heart attacks and stroke in those at high risk for cardiovascular events?

In reality, this is an opinion piece published in a questionable journal* without any new research, and it is the opinion of a collection of well-known (approaching notorious) statin denialists, members of a cult-like organization called The International Network of Cholesterol Skeptics.(THINCS).

Larry Husten, who writes highly informed cardiac journalism at Cardiobrief, gives a good summary of their methods in this description of the authors of an editorial attacking the results of the JUPITER trial:

Nevertheless, the association of the authors with a group like THINCS raises some troublesome questions because, in fact, THINCS members don’t just object to one trial (JUPITER), or just one drug (rosuvastatin), or just the use of statins for primary prevention. They raise objections about ALL cholesterol-lowering trials, ALL cholesterol-lowering drugs, and the use of statins in ALL populations. They constantly harp on the dangerous side effects of  statins, and exploit any bit of evidence they can find to launch their attacks, always ignoring the considerable evidence that doesn’t support their views. So the Archives paper on JUPITER is not really part of the scientific process, since the authors have no interest in the give and take of medicine and science. Their only interest is to attack, at any point, and on any basis, anything related to mainstream science about cholesterol.

The lead and corresponding author, Uffe Ravnskov is the founder of THINCS and author of The Cholesterol Myths – Exposing the Fallacy that Saturated Fat and Cholesterol Cause Heart Disease (2000), which is considered the bible of cholesterol contrarianism.

Ravnskov’s book has been severely criticized in Bob Carroll’s The Skeptic’s Dictionary, which outlines the distortions and deceptive techniques found in the cholesterol skeptics’ arguments.

Harriet Hall wrote an excellent analysis of THINCS 10 years ago at Science-Based Medicine and her concluding sentences are still highly relevant:

“to reject the cholesterol connection and statins entirely is to throw the baby out with the bathwater. In my opinion, THINCS is spreading misinformation that could lead patients to refuse treatment that might prolong their life or at least prevent heart attacks and strokes.”

Indeed, if they were able to convince a highly intelligent patient like Geo, with a science background who also had easy access to the advice of a forward thinking cardiologist to stop taking his statins, who knows how many thousands have been convinced to stop their medications.

So my best advice for Geo and all of you taking statins is the following:

  1. Make sure you really need to be on the drug after engaging in shared-decision making with your physician and learning all you can about your personal risk of cardiovascular disease, the benefits of statins for you, and the potential side effects.
  2. Once you’ve made a decision based on good information and physician recommendation, try to ignore the latest headlines or internet stories that imply some new and striking information that impacts your health-most of these are unimportant.

The evidence for the benefit of statins is based on a deep body of scientific work, which will not be changed by any one new study. There is a very strong consensus amongst scientists who are actively working in the field of atherosclerosis, and amongst physicians who are actively caring for patients, that statins are very beneficial and safe. This consensus is similar to the consensus about the value of vaccines.

Science moves incrementally, and new studies inform those with open minds. The studies in this area that have been most significant in the last few years have actually strengthened the concept that drugs which lower LDL-C without causing other issues lower cardiovascular risk (see here on PCSK9 inhibitors and here on ezetimibe.)

Incrementally Yours,

-ACP

N.B. *The Expert Review of Clinical Pharmacology”is an open access journal, many of which are predatory. Article are solicited and the authors pay to have their work published. For the article in question, the Western Vascular Institute payed the fee. It’s not clear that there is any peer-review process involved.

Some authors have suggested predatory journals are “the biggest threat to science since the inquisition”and I am very worried about the explosive growth in these very weak journals which exist solely to make money.

I realize that writing this piece will engender the wrath of many so before you leave comments impugning my integrity let me reiterate that I receive absolutely nothing from BIG PHARMA. In fact, by writing appropriate prescriptions for statin drugs I reduce my income as my compliant patients avoid hospital and office visits and all kinds of procedures for heart attacks and strokes!

Coronary Artery Calcium Scan Embraced By New AHA/ACC Cholesterol Guidelines: Will Insurance Coverage Follow?

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.

I recommend reading “Are you on the fence about taking a statin drug” to understand the details of using CAC in decision-making and the follow up post on a compromise approach to reducing ASCVD risk.

Deriskingly Yours,

-ACP

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 

-4.4.1.4. 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 (S4.4.1.4-1–S4.4.1.4-8). 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 (S4.4.1.4-9–S4.4.1.4-12). 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 (S4.4.1.4-13). With increasing age, 10- year risk accompanying CAC scores of 1 to 99 rises, usually crossing the 7.5% threshold in later middle age (S4.4.1.4-13). When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years (S4.4.1.4-14–S4.4.1.4-16). 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 (S4.4.1.4-17). A prospective randomized study of CAC scoring showed improved risk factor modification without an increase in downstream medical testing or cost (S4.4.1.4-18). 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 (S4.4.1.4- 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

Should You Take A Statin If You Are Over 75?: The Value of DeRisking in The Elderly

The NY Times published an article earlier this month with the provocative title “You’re Over 75, and You’re Healthy. Why Are You Taking a Statin?”

It’s actually a balanced presentation of this difficult question (although it includes the seemingly obligatory anecdote of a patient getting severe muscle aches and weakness on Lipitor) and I agree with the concept that patients should demand a good thoughtful explanation from their PCP if they are on a statin.  Shared  physician and patient decision-making should occur irrespective of age when a statin is prescribed.

Unfortunately, the NY Times piece was triggered by and contains references to a weak observational study that was recently published in the Journal of  the American Geriatric Society..

A much better article on this same topic was published earlier in January in what is arguably the most respected cardiology journal in the world (Journal of the American College of Cardiology).

It contains what I think is a very reasonable discussion of the problem: the elderly at are a substantially higher risk of adverse “statin-associated symptoms” but also at much higher risk of stroke, heart attack and cardiovascular-related death than the young.

Key Points To Consider For Use of Statins In Elderly

Some key points from that article to ponder for those over 75 years

  1. Major European and North Americans national guidelines differ markedly in this area as this graphic illustrates

“At one end of the spectrum, the 2016 ESC/EAS guidelines miss great opportunities for safe, cheap, and evidence-based prevention in elderly individuals 66 to 75 years of age. At the other end of the spectrum, the 2014 NICE guideline provides near-universal treatment recommendations well into the very elderly >75 years of age where RCT evidence is sparse and more uncertain.”

2. Data on from 2 large primary prevention trial (JUPITER and HOPE-3) show that rosuvastatin (Ridker, et al)

reduced the risk of a composite endpoint (nonfatal MI, nonfatal stroke, or cardiovascular death) substantially by 49% (RR: 0.51; 95% CI: 0.38 to 0.69), and the risk was reduced by 26% (RR: 0.74; 95% CI: 0.61 to 0.91) in those ≥70 years of age. The efficacy was similar in individuals ≥70 and <65 years of age, indicating little heterogeneity in treatment effect by age. Today, nearly all apparently healthy elderly individuals have RCT evidence supporting statin efficacy.

3. The elderly compared to the younger are much more likely to have a nonfatal event  which does not reduce their longevity but impacts their quality of life.

Thus, patient preferences are critical important for well-informed shared decision-making. If a patient only values longevity, there are little data to support primary prevention with statins in people >65 years of age. On the other hand, if preventing nonfatal and potentially disabling MI or stroke is of value to the patient, it might be reasonable to initiate statin therapy. From this perspective, it is noteworthy that the relative importance that people assign to avoiding death compared with avoiding nonfatal events appears to be highly age dependent. Although younger individuals <65 years of age weigh avoiding death highest, elderly individuals ≥65 years put a much higher weight on avoiding MI or stroke than death, These differences are compatible with elderly individuals having a greater focus on quality of life and avoiding disability than on extending life.

The Value of Derisking and Deprescribing

In my practice, I do a fair amount of deprescribing statins in the elderly. I have a very low threshold for initiating a trial  of temporary statin cessation if there is any question that a patient’s symptoms could be statin-related (see here.)

The older the patient, the higher the bar for initiating statins and I think in all patients a search for subclinical atherosclerosis (coronary calcium scan or vascular ultrasound) helps inform the decision.

Previously, I had no term for this higher bar but I like the  term  the  JACC paper introduces, derisking:

A promising approach to personalize treatment in elderly people is “derisking” by use of negative risk markers (i.e., absence of coronary artery calcification) to identify those at so low risk that statin therapy may safely be withheld . In the BioImage study of elderly individuals, for example, absence of coronary artery calcification was prevalent (≈1 of 3) and associated with exceptionally low ASCVD event rates

If you are >75 ponder all these factors and have an intense discussion with your doctor about taking a statin.

If you are still on the fence after this discussion consider a compromise approach that I have outlined here.

Deriskingly Yours,

-ACP

Do Statins Cause Memory Loss? The Science, The Media, The Statin-Denialist Cult, and The Nocebo Effect

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

Antinocebonically Yours

-ACP

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!

For a nice discussion of Nissen’s article see Larry Husten’s excellent piece at Cardiobrief.org here (/nissen-calls-statin-denialism-a-deadly-internet-driven-cult/)

 

Unsure About Taking A Statin For High Cholesterol? Consider A Compromise Approach

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

  1. Cigarette Smoking (by far the strongest)
  2. Diet
  3. Exercise
  4. Obesity (Obviously related to #1 and #2)
  5. Stress
  6. Sleep

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.

Faithfully Yours,

-ACP