All posts by Dr. AnthonyP

Cardiologist, blogger, musician

Putting The Apple Watch 4 ECG To The Test In Atrial Fibrillation: An Informal Comparison To Kardia

My first patient this morning, a delightful tech-savvy septagenarian with persistent atrial fibrillation told me she had been monitoring her rhythm for the last few days using her Apple Watch 4’s built in ECG device.

Previously she had been using what I consider the Gold Standard for personal ECG monitoring- AliveCor’s Kardia Mobile ECG   and I monitored her recordings through our Kardia Pro connection.

I had been eagerly awaiting Apple’s roll out since I purchased the AW4 in September (see here) and between patients this morning I down-loaded and installed the required iPhone and Watch upgrades and began making AW4 recordings.

Through the day I tried the AW4 and the Kardia on patients in my office.

Apple Watch 4 ECG Is Easy and Straightforward

The AW4 ECG recording process is very easy and straightforward. Upon opening the watch app you are prompted to open the health app on your iPhone to allow connection to the Watch ECG information. After this, to initiate a recording simply open the Watch ECG app and hold your finger on the crown.

Immediately a red ECG tracing begins along with a 30 second countdown.

Helpful advice to pass the time appears below the timer:

“Try Not to move your arms.”

and

“Apple Watch never checks for heart attacks.”

When finished you will see what I and my patient (who mostly stays in sinus rhythm with the aid of flecainide) saw-a declaration of normality:

Later in the day I had a few patients with permanent  atrial fibrillation put on my watch.

This seventy-something farmer from Bowling Green, Missouri was easily able to make a very good ECG recording with minimal instruction

 

 

 

 

The AW4 nailed the diagnosis as atrial fibrillation.

We also recorded a Kardia device ECG on him and with a little more instruction the device also diagnosed atrial fibrillation

 

 

After you’ve made an AW4 recording you can view the PDF of the ECG in the Health app on your iPhone where all of your ECGs are stored. The PDF can be exported to email (to your doctor) or other apps.

ECG of the Bowling Green farmer. I am not in afib.

 

Apple Watch Often “Inconclusive”

The AW4 could not diagnose another patient with permanent atrial fibrillation and judged the recording “inconclusive”

The Kardia device and algorithm despite a fairly noisy tracing was able to correctly diagnose atrial fibrillation in this same patient.

 

 

I put the AW4 on Sandy, our outstanding echo tech at Winghaven who is known to have a left bundle branch block but remains in normal rhythm and obtained this inconclusive report .

 

 

 

 

Kardia, on the other hand got the diagnosis correctly:

 

 

 

 

One Bizarre Tracing by the AW4

In another patient , an 87 year old lady with a totally normal recording by the Kardia device, the AW4 yielded a bizarre tracing which resembled ventricular tachycardia:

Despite adjustments to her finger position and watch position, I could not obtain a reasonble tracing with the AW4.

The Kardia tracing is fine, no artifact whatsoever.

 

 

 

 

 

 

 

 

 

What can we conclude after today’s adventures with the Apple Watch ECG?

This is an amazingly easy, convenient and straightforward method for recording a single channel ECG.

I love the idea that I can record an ECG whereverI am with minimal fuss. Since I wear my AW4 almost all the time I don’t have to think about bringing a device with me (although for a while I had the Kardia attached to iPhone case that ultimately became cumbersome.)

Based on my limited sample size today, however, the AW4 has a high rate of being uncertain about diagnoses. Only 2/3 cases of permanent atrial fibrillation were identified (compared to 3/3 for the Kardia) and only 4/6 cases of sinus rhythm were identified.

If those numbers hold up with larger numbers, the AW4 is inferior to the Kardia ECG device.

I’d rather see the AW4 declare inconclusive than to declare atrial fibrillation when it’s not present but this lack of certainty detracts from its value.

What caused the bizarre artifact and inconclusive AW4 tracing in my patient is unclear. If anybody has an answer, let me know.

We definitely need more data and more studies on the overall sensitivity and specificity of the AW4 and hopefully these will be rapidly forthcoming.

For most of my patients the advantages of the AW4 (assuming they don’t already have one) will be outweighed by its much greater cost and we will continue to primarily utilize the Kardia device which will also allow me to view all of their recordings instantaneously in the cloud.

Conclusively 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!

Who Deserves To Be A Wikipedia Article?: The Deletion of Dr. Malcolm Kendrick

Scottish primary care physician and author of The Great Cholesterol Con Dr. Macolm Kendrick began his blog post yesterday with these words:

I thought I should tell you that I am about to be deleted from Wikipedia. Someone sent me a message to this effect. It seems that someone from Manchester entitled User:Skeptic from Britain has decided that I am a quack and my presence should be removed from the historical record.

Although I don’t agree with Kendrick’s statin denialism I do find him an informative, entertaining and different voice in the field of atherogenesis and it didn’t seem right that he should be deleted from Wikipedia.

Apparently, articles on Wikipedia can be proposed for deletion and at Wikipedia: Articles for deletion/Malcolm Kendrick there is an ongoing battle between the forces fighting for deletion of kendrick those fighting for maintenance of his Wikipedia entry.

This wikipedia comment is what initiated the deletion proposition:

Malcolm Kendrick is a fringe figure who agues(sic) against the lipid hypothesis. He denies that blood cholesterol levels are responsible for heart disease and in opposition to the medical community advocates a high-fat high-cholesterol diet as healthy. Problem is there is a lack of reliable sources that discuss his ideas. His book The Great Cholesterol Con was not reviewed in any science journals. Kendrick is involved with the International Network of Cholesterol Skeptics, I suggest deleting his article and redirecting his name to that. Skeptic from Britain (talk) 20:29, 2 December 2018 (UTC)

I have no idea what are valid criteria are for a human becoming an article on Wikipedia (in fact I’ve often thought that I should have an article) but none of the “Skeptic from Britain’s” arguments would sway me to delete Kendrick’s article.

Wikipedically Yours,

-ACP

The Marvelous Marion Nestle’ and Her Food Politics: From A2 Milk to Helpful Hops

The skeptical cardiologist follows a few blogs/websites regularly because they provide consistently good commentary or reporting on topics I’m focused on.

Prominent among these is http://www.foodpolitics.com which Marion Nestle’* writes.

Almost every post that she creates provides me with unique and fascinating information or understanding about food and the food industry.

Let me take a few recent examples.

Farmer’s Share of Thanksgiving Dinner.

On Thankgiving Nestle’ highlighted this report from the National Farmer’s Union which revealed that farmer’s get only 11 cents from the typical American family’s Thanksgiving dinner. It’s a particularly low portion of the overall money spent on the turkey that goes to farmers because:

“The major integrators who control the poultry markets have used their extreme bargaining power to suppress the earnings of the men and women who raise our chickens and turkeys while simultaneously taking in record profits for themselves,” Johnson said. “While poultry growers take all the risk of production, they are receiving just 5 to 6 cents per pound for turkeys and chickens. The integrators take those same turkeys and chickens, process them, and then mark up the retail value nearly tenfold.”

Capture-78-500x648

A2 Milk: Healthier?

Nestle’ has written extensively about the pervasive influence of the food industry on nutritional research in her books including her recently published Unsavory Truth: How Food Companies Skew the Science of What We Eat.

She has long been at the forefront in pointing out that industry-sponsored research is highly likely to be favorable to the product the industry sells.

A2 milk, which has taken over a large share of the Australia and New Zealand dairy market based on shaky scientific studies which suggest it is healthier than the standard A1 milk is now being promoted in the US.

A recent Nestle’ post points out that

 claims for A2 milk’s better digestibility were based entirely on studies paid for by—surprise!—the manufacturer (as I explain in my latest book, Unsavory Truth: How Food Companies Skew the Science of What We Eatfood industry funding of nutrition research produces highly predictable results and, therefore, is not good for science, public health, or trust)

Stripping the Healthy Polyphenols From Corn

Nestle’ wrote recently of a study sponsored by Kellogg’s which demonstrated what happens to the healthy phytosterols in corn when it is processed:

In FoodNavigator, I read a report of a study finding that processing of corn into breakfast cereal flakes strips out phenolic compounds and tocopherols (vitamin E) associated with good health.

Just as processing of whole wheat into white flour removes the bran and germ, so does the processing of corn into corn flakes.

The germ and bran (hull) layers of grain seeds contain the vitamins and minerals—and the phenolics.  What’s left is the starch and protein (endosperm).

To replace these losses, manufacturers fortify corn flakes with 10% to 25% of the Daily Value for 12 vitamins and minerals.

This study is further evidence for the benefits of consuming relatively unprocessed foods.

Of particular interest to me is the authors’ disclosure statement:

This work was funded in part through gifts from the Kellogg Company and Dow AgroSciences.

The authors declare no competing financial interest.

This makes this study a highly unusual example of an industry-funded study with a result unfavorable to the sponsor’s interests.  The authors do not perceive Kellogg funding as a competing interest.  It is.  Kellogg (and maybe Dow) had a vested interest in the outcome of this study.

Beer Hops and Alzheimer’s

One of Nestle’s posts caught my eye as she mentioned a Japanese study**  which showed that beer hops help mice with Alzheimer’s.

If the findings hold true in humans we should all be chugging hoppy  IPAs with really high IBUs as the paper concluded:

The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer’s disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia.

Sadly, we must take this paper with a grain of malt, as the lead author works at “Research Laboratories for Health Science & Food Technologies, Kirin Company Ltd.” Kirin being a prominent Japanese brewery.

Nestle’s posts are short, well-referenced and consistently high quality.

I’m going to update my “blogroll” (something I’ve failed to do for several years) with Food Politics and I highly recommend signing up for email delivery of her posts if you are interested in food, nutrition and the interaction between the food industry and nutritional science.

Lupulusly Yours,

-ACP

N.B.

*Marion Nestle is Paulette Goddard Professor of nutrition, food studies, and public health, emerita, at New York University, and Visiting Professor of nutritional sciences at Cornell. She has a PhD in molecular biology and an MPH in public health nutrition from UC Berkeley. She lives in New York City.

**Nestle’s post actually references a different Kirin sponsored study in mice (Matured Hop-Derived Bitter Components in Beer Improve Hippocampus-Dependent Memory Through Activation of the Vagus Nerve) than the one I reference above which was truly related to Alzheimer’s.

 

Skeptical Cardiologist Lowers His Cardiovascular Risk By Marrying The Eternal Fiancee’

The skeptical cardiologist shed his skepticism about marriage today and tied the knot with his Eternal Fiancee’.

This decision was not based on the findings of a recent meta-analysis of 34 studies with more than two million participants that found that that compared with married people, those who were unmarried  ( never married, widowed or divorced)  were 42 percent more likely to have some form of cardiovascular disease and 16 percent more likely to have coronary heart disease.

No, I was not influenced by these observational data which show a 43% increase risk of coronary heart disease death and a 55% increased risk of death from stroke.

Headlines like this from Time magazine:

How Marriage Can Actually Protect Your Heart Health

had no bearing on my decision.

This skeptical cardiologist found the perfect woman for his skeptical ways,

And observations that unmarried patients have longer delays in seeking medical help which influences the timing and benefit of invasive cardiac procedures that reduce mortality played no role in this decision.

Neither did the prospect that a spouse would encourage a more healthy lifestyle and better adherence to treatment nor the buffering hypothesis which suggests that informational or emotional resources from a spouse promote adaptive behaviour and may reduce excessive neuroendocrine response to acute or chronic stressor.

Nope. It was pure and unadulterated love.

Blissfully Yours,

-ACP

Becoming Enlightened About More Stringent Blood Pressure Goals: Sapere Aude!

The skeptical cardiologist and many of his patients with hypertension have a decision to make: what should our BP goal be?

Given that we have data now on over 1 million patients one might think that the answer would be clear and that there would be a consensus amongst all the experts.

Messerli and Bangalore, writing in a recent special hypertension issue of JACC, however, clearly articulate the “blood pressure landscape schism” that currently exists.

This figure from their paper (subtitled “Schism Among Guidelines, Confusion Among Physicians, and Anxiety Among Patients”) shows the marked difference in BP goal and treatment recommendations for the same patient in recent American and  European Cardiology and American Family Practice Guidelines.

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines—which aide approximately 25,000 cardiologists in the United States—indicate that her BP should be <130/80 mm Hg (1). The 2018 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines—which aide approximately 75,000 physicians—indicate that her BP should be <140/90 mm Hg (2). The 2017 American College of Physicians (ACP)/American Association of Family Physicians (AAFP) guidelines—which aide approximately 250,000 family practitioners and internists in the United States—indicate that her BP should be <150/90 mm Hg

 

 

 

 

 

 

 

 

 

 

 

Messerli and Bangalore use a second figure to graphically illustrate the potential consequences of the differing guidelines.

Stroke Mortality for Upper Limit of On-Treatment Systolic Target BP as per Various Guidelines Absolute risk of stroke mortality is 5% for the suggested on-treatment target BP of the ACC/AHA guidelines, 8% for target BP of the ESH/ESC guidelines, and 14% for target BP of the ACP/AAFP guidelines. Abbreviations as in

Cardiovascular death rates thus may vary three-fold depending on what BP goal we choose.

This marked variation in treatment recommendation highlights that they

are not only an evaluation and interpretation of evidence in question, but also a judgment weighted by personal, regulatory, and organizational preferences that can vary from physician to physician within a country and across geographical regions.

Physicians and patients (hopefully through shared decision making) are going to have to do some thinking on their own.

Messerli and Bangalore quote Immanuel Kant in this regard:

Enlightenment is man’s emergence from his self-imposed nonage. Nonage is the inability to use one’s own understanding without another’s guidance. This nonage is self-imposed if its cause lies not in lack of understanding but in indecision and lack of courage to use one’s own mind without another’s guidance. Dare to know! (Sapere aude.) “Have the courage to use your own understanding,” is therefore the motto of the enlightenment.

As a 64 year old who has emerged from his nonage with hypertension, I have carefully examined the latest American hypertension guidelines especially in light of the SPRINT study and elected to add a third anti-hypertensive agent to get my average BP below 130/80. It’s worked for me with minimal  side effects but I carefully monitor my BP.

If I notice any symptoms (light-headed, fatigued) suggesting hypotension associated with systolic BP <120 mm Hg I tweak my medical regimen to allow a higher BP.

Like all of my patients I would prefer to be on less medications, not more but when it comes to enlightenment about the effects of hypertension, it is now clear that lower is better for most of us in our sixties down to at least 130/80*.

Sapere Audaciously Yours,

-ACP

*N.B. In the SPRINT study the BP was obtained using an automatic BP cuff after 5 minutes of rest with the patient unobserved and averaging 3 recordings one minute apart.

This “research grade BP” averages about 12 mm Hg less than a routine single clinic obtained BP (see here.)

The BP Schism

What Can You Really Learn From Celebrity Bob Harper’s Heart Attack And Near Sudden Death?

Until recently I had never heard of Bob Harper (The Biggest Loser) but apparently he is a celebrity personal trainer and had a heart attack and nearly died.  He  is known “for his contagious energy, ruthless training tactics, and ability to transform contestants’ bodies on The Biggest Loser” (a show I’ve never seen.)

When celebrities die suddenly (see Garry Sanders, Carrie Fischer) or have a heart attack at a youngish age despite an apparent healthy lifestyle this get’s people’s attention.

The media typically pounce on the story which combines the seductive allure of both health and celebrity reporting.

It turns out Harper inherited a high Lipoprotein (a) (see here) which put him at high risk for coronary atherosclerosis (CAD) which ultimately caused the heart attack (MI)  that caused his cardiac arrest.

To his credit, Harper has talked about Lipoprotein (a) and made the public and physicians more aware of this risk factor which does not show up in standard cholesterol testing.

Since his heart attack, Mr. Harper of “The Biggest Loser” has embarked on a newfound mission to raise awareness about heart disease and to urge people to get tested for lp(a).

Harper As Brilinta Shill

Unfortunately , he has also become a shill for Brilinta, an expensive brand name anti platelet drug often prescribed in patients after heart attacks or stents.

At the end of the TV commercial he says “If you’ve had a heart attack ask your doctor if Brilinta is right for you. My heart is worth Brilinta.”

At least this video is clearly an advertisement but patients and physicians are inundated  by infomercials for expensive, profit-driving drugs like Brilinta.

This Healthline article pretends to be a legitimate piece of journalism but is a stealth ad for Brilinta combined with lots of real ads for Brilinta.

Harper As Lifestyle Coach.

Harper also changed his fitness and diet regimens after his MI reasoning that something must have been wrong with his lifestyle and it needed modification.  For the most part he talks about more “balance” in his life which is good advice for everyone. His fitness regimens pre-MI were incredibly intense and have been toned down subsequently.

After his heart attack, Bob abandoned the Paleo lifestyle for the Mediterranean diet, as it’s been proven to improve heart health and reduce the risk of a heart attack, stroke, and heart-disease-related death by about 30 percent. But recently, he’s moved closer to a vegetarian regimen.

Of course, vegans and vegetarians have seized on this change in his diet as somehow proving the superiority of their chosen diets as in this vegan propaganda video:

Unfortunately there is no evidence that changing to a vegan or vegetarian diet will lower his risk of repeat MI.  Those who promote the Esselstyn, Pritikin or Ornish type diets claim to “reverse heart disease” and to be science-based but, as I’ve pointed  out (see here) the science behind these studies is really bad.

In fact, we know that neither diet nor exercise influence lipoprotein(a) levels which Bob inherited.  Some individuals just inherit the risk and must learn to deal with the cardiovascular cards they’ve been dealt.

What Can We Really Learn From Bob Harper’s Experience?

  1. Lipoprotein (a) is a significant risk marker for early CAD/MI/sudden cardiac death. Consider having it measured if you have a a) strong family history of premature deaths/heart attack (b) if you have developed premature subclinical atherosclerosis (see here) or clinical atherosclerosis (heart attack, stroke, peripheral vascular disease) or (c) a family member has been diagnosed with it.
  2. Everyone should learn how to do CPR and how to utilize an AED. (see here for my rant on these two incredibly important 3-letter words). Harper was working out in the gym when he collapsed. Fortunately a nearby medical student had the wherewithal to do CPR on him until he could be defibrillated back to a normal rhythm and transported to a hospital to stop his MI.
  3. Dropping dead suddenly is often the first indicator that you have advanced CAD. If you have a strong family history of sudden death or early CAD consider getting a coronary artery calcium scan to better assess your risk.

Focus on celebrities with heart disease helps bring awareness to the public about important issues but we can only learn so much about best lifestyle or medications from the experience of one individual, no matter how famous.

Brilliantly Yours,

-ACP

Has REDUCE-IT Resurrected Fish OIl Supplements (And Saved Amarin)?

The answers are no and yes.

There is still no reason to take over the counter fish oil supplements.

In fact, a study published Saturday found that fish oil supplementation (1 g per day as a fish-oil capsule containing 840 mg of n−3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]

did not result in a lower incidence than placebo of the primary end points of major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type.

However, another study  published Saturday (REDUCE-IT) and presented at the annual American Heart Association Scientific Sessions to great fanfare found that an ethyl-ester formulation (icosapent ethyl) of eicosapentanoic acid (EPA, one of the two main marine n-3 fish oils)  reduced major cardiovascular events by 25% in comparison to placebo.

When I wrote about Icosapent ethyl (brand name Vascepa) in a previous blog post in 2015 there was no data supporting its use:

A fish oil preparation, VASCEPA,  available only by prescription, was approved by the FDA in 2012.

Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides(>500 mg/dl).

This is a very small market compared to the millions of individuals taking fish oil thinking that  it is preventing heart disease.

The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.

The company has a study that shows that Vascepa lowers triglycerides in patients with such mildly to moderately elevated triglycerides but the FDA did not approve it for that indication.

Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.

After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.

Data do not exist to say that lowering triglycerides in the mild to moderate range  by any drug lowers heart attack risk.

In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amarin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.

Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amarin, has stock in the company (Vascepa is the sole drug made by Amarin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amarin.

If he answers no to all of the above then, hopefully, your triglycerides are over 500.

And although elevated triglycerides confer an elevated CV risk nearly all prior trials evaluating different kinds  of triglyceride-lowering therapies, including extended-release niacin, fibrates, cholesteryl ester transfer protein inhibitors, and omega-3 fatty acids have failed to show reductions in cardiovascular events

REDUCE-IT, Amarin trumpeted widely in September (before the actual data was published)  now provides impressive proof that it prevents cardiovascular disease. Has the skeptical cardiologist changed his mind about fish oil?

Vascepa Is Not Natural Fish Oil

Although Amarin’s marking material states “VASCEPA is obtained naturally from wild deep-water Pacific Ocean fish” the active ingredient is an ethyl ester form of eicosapentoic acid (EPA) which has been industrially processed and distilled and separated out from the other main omega-3 fatty acid in fish oil (DHA or docosohexanoieic acid).

Natural fish oil contains a balance of EPA and DHA combined with triacylglycerols (TAGS).

So even if the REDUCE-IT trial results can be believed they do not support the routine consumption of  over the counter fish oil supplements for prevention of cardiovascular disease.

Does REDUCE-IT  Prove The Benefit of Purified High Dose EPA?

REDUCE-IT was a large (8179 patients) randomized, double-blind placebo controlled trial

Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter  and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter  and had been receiving a stable dose of a statin for at least 4 weeks. In 2013 the protocol was changed and required a triglyceride level>200 mg/dl.

Participants were randomized to icosapent ethyl (2 g twice daily with food [total daily dose, 4 g]) or a placebo that contained mineral oil to mimic the color and consistency of icosapent ethyl and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group.

More importantly, the hard end-points of CV death, nonfatal stroke and heart attack were also significantly lower in the Vascepa arm compared to the “placebo” arm.

These results are almost unbelievably good and they are far better than one would have predicted given only a 17% reduction in triglycerides.

This makes me strongly consider prescribing Vascepa (something I heretofore have never done) to my higher risk patients with triglycerides over 200 after we’ve addressed lifestyle and dietary contributors.

Perhaps the high dose of EPA (4 grams versus the 1 gram utilized in most trials) is beneficial in stabilizing cell membranes, reducing inflammation and thrombotic events as experimental data has suggested.

Lingering Concerns About The Study

Despite these great results I have some concerns:

  1. The placebo contained mineral oil which may not have been neutral in its effects. In fact, the placebo arm had a significant rise in the LDL cholesterol.
  2. Enrolled patients were predominantly male and white. No benefit was seen in women.
  3. Higher rates of serious bleeding were noted in patients taking Vascepa
  4. Atrial fibrillation developed significantly more often in Vascepa patients (3.1%) versus the mineral oil patients (2.1%)

Finally, the trial was sponsored by Amarin Pharma. This is an aggressive company that I don’t trust.  The steering committee consisted of academic physicians (see the Supplementary Appendix), and representatives of the sponsor developed the protocol,  and were responsible for the conduct and oversight of the study, as well as the interpretation of the data. The sponsor was responsible for the collection and management of the data. All the data analyses were performed by the sponsor,

After i wrote my negative piece on Vascepa in 2015 a number of Amarin investors attacked me because Vascepa is the only product Amarin has and any news on the drug dramatically influences its stock price. Here is the price of Amarin stock in the last year.

The dramatic uptick in September corresponds to the company’s announcement of the topline results of REDUCE-IT. Since the actual results have been published and analyzed the stock has dropped 20%.

High Dose Purified and Esterified EPA-Yay or Nay?

I would love to see another trial of high dose EPA that wasn’t totally under the control of Amarin and such trials are in the pipeline.

Until then, I’ll consider prescribing Amarin’s pills to appropriate patients* who can afford it and who appear to have significant residual risk after statin therapy*.

But, I will continue to tell my patients to stop paying money for useless OTC fish oil supplements.

Megaskeptically Yours,-

ACP

N.B.* Appropriate patients will fit the entry criteria for REDUCE-IT described below.

Patients could be enrolled if they were 45 years of age or older and had established cardiovascular disease or were 50 years of age or older and had diabetes mellitus and at least one additional risk factor. Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter (1.69 to 5.63 mmol per liter) and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter) and had been receiving a stable dose of a statin for at least 4 weeks;

So either secondary prevention (prior heart attack or stroke) or primary prevention in patients with diabetes and another risk factor.

 

 

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

The Painful EHR Transition

For the past 6 weeks I and the several hundred other ambulatory  physicians who belong to the St. Luke’s Medical Group have been going through a difficult transition; we’ve changed the software that we use to manage patient information.

Seven years ago we made the painful transition from paper patient charts to an electronic health record (EHR) called eClinical Works. This process required lots of scanning but by 2015 when i wrote “I Absolutely Love and Abhor My EMR” I had become very facile and comfortable with the software.

During this current transition to an EHR called Cerner,  we had to drastically reduce the number of patients seen per day in the office as we learned how to streamline workflow and as bugs were worked out of the system. We have struggled mightily with the simplest of tasks such as renewing patient prescriptions, scheduling tests, or reviewing test results. Stress levels for everyone, assistants to physicians, went through the roof as we spent hours clicking, refreshing, and re-entering data ion our frequently crashing computers.

My apologies to all the patients that had to be rescheduled during this process and to any who had to wait excessively for something as simple as a follow up appointment. The bugs aren’t completely out but we are making progress.

And my apologies to readers of the skeptical cardiologist as this EHR transition plus other work and social demands have left me no time to write.

Atul Gawande, a surgeon and excellent writer has written a great piece for the New Yorker entitled “The Upgrade: Why doctors hate their computers.” which nicely details why doctors have reached a point where they  “actively, viscerally, volubly hate their computers.”

Prior to our Cerner transition I was in a good relationship with my various Mac laptops but for the last 6 weeks interacting with the EHR has made me a stressed, anxious and borderline depressed physician.

I am only 6 weeks into the new EHR but Gawande, who has been using Epic* since 2015 writes that “I’ve come to feel that a system that promised to increase my mastery over my work has, instead, increased my work’s mastery over me.”

“A 2016 study found that physicians spent about two hours doing computer work for every hour spent face to face with a patient-whatever the brand of medical software. In the examination room, physicians devoted half of their patient time facing the screen to do electronic tasks. These tasks spill over after hours and the result has been epidemic levels of burnout among clinicians.”

The first 6 months of any EHR transition are by far the most difficult as all users gain proficiency with the workflow and as most patients are newly entering the system.  Hopefully, 6 months from now the computer will not be my master and I and my staff will not be burned out.

Skeptically Yours,

-ACP

*Epic is the most widely used EHR by ambulatory physicians. Gawande makes the claim that “more than half of Americans have their health information in the Epic system. ” This graph indicates Epic is definitely the market leader but seems to have less than 50% of patients.

 

On the other hand, this recent report indicates that ” Cerner leads the worldwide EHR market with Epic taking the second spot, Allscripts in third and GE Healthcare at fourth.”