Tag Archives: coronary stents

Top Skeptical Cardiology Stories of 2017

Science continued to progress in the field of cardiology in 2017. Some cardiology interventions were proven to be more beneficial (TAVR) and some less (coronary stents). A class of cholesterol lowering drugs had a big winner and a big loser. A supplement that many thought, based on observational studies, was crucial to prevent heart disease, turned out to be unhelpful. More evidence emerged that saturated fat is not a dietary villain.

From the skeptical cardiologist’s viewpoint, the following were the major scientific studies relevant to cardiology:

1.  “Thousands of heart patients get stents that may do more harm than good”

Thus read the Vox headline for the ORBITA study which was published in November.

Indeed this was an earth-shattering study for interventional cardiologists, many of whom agreed with the NY Times headline “Unbelievable: Heart Stents Fail To Ease Chest Pain.”

Cardiologists have known for a decade (since the landmark  COURAGE study) that outside the setting of an acute heart attack (acute coronary syndrome or ACS), stents don’t save lives and that they don’t prevent heart attacks.

Current guidelines reflect this knowledge, and indicate that stents in stable patients with coronary artery disease should be placed only after a failure of  “guideline-directed medical therapy.”  Despite these recommendations, published in 2012, half of the thousands of stents implanted annually in the US continued to be employed in patients with either no symptoms or an inadequate trial of medical therapy.

Yes, lots of stents are placed in asymptomatic patients.  And lots of patients who have stents placed outside the setting of ACS are convinced that their stents saved their lives, prevented future heart attacks and “fixed” their coronary artery disease. It is very easy to make the case to the uneducated patient that a dramatic intervention to “cure” a blocked artery is going to be more beneficial than merely giving medications that dilate the artery or slow the heart’s pumping to reduce myocardial oxygen demands.

Stent procedures are costly  in the US (average charge around $30,000, range $11,000 to $40,000) and there are significant risks including death, stroke and heart attack. After placement, patients must take powerful antiplatelet drugs which increase their risk of bleeding. There should be compelling reasons to place stents if we are not saving lives.

I, along with the vast majority of cardiologists, still recommended stents for those patients with tightly blocked coronary arteries and stable symptoms, which were not sufficiently helped by medications. ORBITA calls into question even this indication for stenting.

The ORBITA study investigators recruited 230 patients to whom most American cardiologists would have recommended stenting. These patients appeared to have a single tightly blocked coronary artery and had chest pain (angina) that limited their physical activity.

They treated the patients for 6 weeks with aspirin/statins/ and medications that reduce anginal symptoms such as beta-blockers, calcium-channel blockers or long-acting nitrates. At this point patients were randomized to receive either a stent or to undergo a catheteriation procedure which did not result in a stent, a so-called sham procedure.

The performance of a sham procedure was a courageous move that made the study truly double-blinded; neither the patients nor the investigators knew which patients had actually received a stent. Thus, the powerful placebo effects of having a procedure were neutralized.

Surprisingly, the study found that those patients receiving stents had no more improvement in their treadmill exercise time, angina severity or frequency or in their peak oxygen uptake on exercise.

ORBITA hopefully will cause more cardiologists to avoid the “oculo-stenotic” reflex wherein coronary artery blockages are stented without either sufficient evidence that the blockage is causing symptoms or that a medical trial has failed.

Although this was a small study with a very narrowly defined subset of patients, it raises substantial questions about the efficacy of coronary stenting. If ORBITA causes more patients and doctors to question the need for catheterization or stenting, this will be a  very good thing.

2. Vitamin D Supplementation Doesn’t Reduce Cardiovascular Disease (or fractures, or help anything really).

One of my recurring themes in this blog is the gullibility of Americans who keep buying and using useless vitamins, supplements and nutraceuticals, thereby feeding a $20 billion industry that provides no benefits to consumers (see here and here).

Vitamin D is a prime player in the useless supplement market based on observational studies suggesting low levels were associated with increased mortality and cardiovascular disease

Despite well done studies showing a lack of benefit of Vitamin D supplementation, the proportion of people taking more than 1,000 IU daily of Vitamin D surged from just 0.3 percent  in 1999-2000 to 18 percent in  2013-2014.

I’ve written previously (calcium supplements: would you rather a hip fracture or a heart attack) on the increased risk of heart attack with calcium supplementation.

Most recently a nicely done study showed that Vitamin D supplementation doesn’t reduce the risk of heart disease.

In a randomized clinical trial that included 5108 participants from the community, the cumulative incidence of cardiovascular disease for a median follow-up period of 3.3 years was 11.8% among participants given 100 000 IU of vitamin D3 monthly, and 11.5% among those given placebo.

Aaron Carroll does a good job of summarizing the data showing Vitamin D is useless in multiple other areas in a JAMA forum piece:

Last October, JAMA Internal Medicine published a randomized, controlled trial of vitamin D examining its effects on musculoskeletal health. Postmenopausal women were given either the supplement or placebo for one year. Measurements included total fractional calcium absorption, bone mineral density, muscle mass, fitness tests, functional status, and physical activity. On almost no measures did vitamin D make a difference.

The accompanying editor’s note observed that the data provided no support for the use of any dose of vitamin D for bone or muscle health.

Last year, also in JAMA Internal Medicine, a randomized controlled trial examined whether exercise and vitamin D supplementation might reduce falls and falls resulting in injury among elderly women. Its robust factorial design allowed for the examination of the independent and joined effectiveness of these 2 interventions. Exercise reduced the rate of injuries, but vitamin D did nothing to reduce either falls or injuries from falls.

In the same issue, a systematic review and meta-analysis looked at whether evidence supports the contention that vitamin D can improve hypertension. A total of 46 randomized, placebo controlled trials were included in the analysis. At the trial level, at the individual patient level, and even in subgroup analyses, vitamin D was ineffective in lowering blood pressure.

Finally, if the Vitamin D coffin needs any more nails, let us add the findings of this recent meta-analysis:

calcium, calcium plus vitamin D, and vitamin D supplementation alone were not significantly associated with a lower incidence of hip, nonvertebral, vertebral, or total fractures in community-dwelling older adults.

3. PCSK9 Inhibitors: Really low cholesterol levels are safe and reduce cardiac events

I reported the very positive results for evolocumab and disappointing results for bosocizumab on the physician social media site SERMO in March but never put this in my blog.

As a practicing cardiologist I’ve been struggling with how to utilize the two available PCSK9 inhibitors (Amgen’s Repatha (evolocumab) and Sanofi’s Praluent (alirocumab) in my clinical practice.  I would love to use them for my high risk statin-intolerant patients but the high cost and limited insurance coverage has resulted in only a few of my patients utilizing it.

The lack of outcomes data has also restrained my and most insurance companies enthusiasm for using them.

The opening session at this year’s American College of Cardiology Scientific Sessions in DC I think has significantly changed the calculus in this area with two presentations: the first showing  Amgen’s “fully humanized” evolocumab significantly lowers CV risk in high risk patients on optimal statin therapy and the second showing that Pfizer’s “mostly humanized” bococizumab loses efficacy over time and will likely never reach the market.

The FOURIER study of evolocumab randomized  27, 564 high risk but stable patients who had LDL>70 with prior MI, prior stroke or symptomatic PAD to receive evolocumab or placebo on top of optimized lipid therapy. 69% of patients were recieving high intensity statin therapy and the baseline LDL was 92. LDL was reduced by 59% to average level of 30 in the treated patients. The reduction in LDL was consistent through the duration of the study.

IN 1/4 of the patients LDL was <20! These are unprecedented low levels of LDL.

Active treatment significantly reduced the primary endpoint by 15% and reduced the secondary endpoinf  of CV death, MI, stroke by 20%. absolute difference 2% by 3 years. 

There was no difference in adverse effects between placebo and Evo. 

The next presentation featured data using Pfizer’s candidate in the PCSK9 wars and the acronym SPIRE (Studies of PCSK9 Inhibition and the Reduction in vascular Events (SPIRE) Bococizumab Development Program).

Paul Ridker presented the outcomes data for bococizumab which was actually similar to evolocumab data but given the declining efficacy and development of antibodies to the Pfizer drug over time these were very disappointing for Pfizer and I would presume their drug will never reach the market.

How will these results impact clinical practice?

I am now more inclined to prescribe evolocumab to my very high risk patients who have not achieved LDL< 70. I’m willing to do what I can to jump through insurance company hoops and try to make these drugs affordable to my patients.

I am less worried about extremely low LDL levels and have more faith in the LDL hypothesis: the lower the LDL the lower the risk of CV disease.

Cost is still going to be an issue for most of my patients I fear and the need for shared decision-making becomes even more important.

 

4. “Pure Shakes Up Nutritional Field: Finds High Fat Intake Beneficial.”

As one headline put it.

I recorded my full observations on this observational international study here

Here is a brief excerpt:

The Prospective Urban Rural Epidemiology (PURE) study, involved more than 200 investigators who collected data on more than 135000 individuals from 18 countries across five continents for over 7 years.

There were three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe)

This was the largest prospective observational study to assess the association of nutrients (estimated by food frequency questionnaires) with cardiovascular disease and mortality in low-income and middle-income populations,

The PURE team reported that:

-Higher carbohydrate intake was associated with an increased risk of total mortality but not with CV disease or CV disease mortality.

This finding meshes well with one of my oft-repeated themes here, that added sugar is the major toxin in our diet (see here and here.)

I particular liked what the editorial for this paper wrote:

Initial PURE findings challenge conventional diet–disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well designed randomised controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility

I wish for all those following science-based medicine a healthy dose of humility. As science marches on, it’s always possible that a procedure we’ve been using might turn out to be useless (or at least much less beneficial than we thought), and it is highly likely that weak associations turn out to be causally nonsignificant. Such is the scientific process. We must continually pay attention, learn and evolve in the medical field.

Happy New Year to Be from the Skeptical Cardiologist the EFOSC!

The skeptical cardiologist and his Eternal Fiancee marveling at the total eclipse of the sun (very accurately predicted by science) in St. Genevieve, Missouri

-ACP

 

Death and Taxus In The Garden of Mildred

A few days ago, the eternal fiancee’ (ETOSC) and I drove from Cardiff-by-the-Sea to the UCLA medical center so that I could undergo a Gallium 68 DOTATATE PET scan.

We arrived at the med-center an hour early and took a walk around Westwood. It was a beautiful, sunny day, in the high 60s, a pleasant contrast to the snowy cold we left behind in St. Louis.

Screen Shot 2016-01-29 at 1.52.51 PMI had spotted on Apple maps a tiny, triangular splash of green labeled “the Mildred Mathias Botanical Garden” and thought this might serve as a pleasant diversion prior to being irradiated.

As we rounded a  corner across from the UCLA campus, the towering medical complex buildings yielded to an unassuming area of lush foliage. We navigated our way across a busy street, followed a small unmarked path and suddenly found ourselves surrounded by a wide and fascinating  variety of taxonomically labeled trees, bushes and flowers.

Mildred Mathias Botanical Garden

This, then,  was the Mildred Mathias botanical garden. I had never heard of Mildred but it turns out she had been an immensely important person in the world of botany, ethnobotany and ecotourism.

mildredMildred (1906-1995) was born and raised (according to her LA Times obituary) “in a small town in the Missouri Ozarks”  (in actuality this was Sappington, now a suburb in  South St. Louis County) and ended up matriculating at Washington University, the college three of my children have attended.   According to the website of the botanical garden:

“There Mildred majored in mathematics until her junior year, but switched to botany when classes for her major were unavailable, and when the Dean of Engineering would not give permission to a woman to take a math course in his male-only college. Fortunately, Mildred was soon hooked on botany, and at Washington University earned the A.B. (1926), M.A. (1927) and Ph.D. (1929) while conducting her graduate research at the Missouri Botanical Garden.”

Quite difficult to comprehend that 90 years ago a woman could not take a class  in the Washington University School of Engineering, the school at which my youngest daughter is now  studying computer science.

During her illustrious career she established herself as an expert in identifying and classifying members of the carrot family (umbellifers)  and, in 1954, an umbellifer  from northeastern Mexico was named as the genus Mathiasella in her honor. Her expertise on umbellifers earned her early international recognition in taxonomy, and in 1964 she was elected as the first woman president of the American Society of Plant Taxonomists.

From Poison To Medicine

In her eponymous gardens, I searched for significant cardiac medicinal plants. I was hoping to encounter the magnificent and legendary foxglove of which I have frequently written.

The_Llangernyw_yew
This is not the English Yew I saw but a massive 1500 year old English Yew, The Langernyw yew in Wales, one of the oldest trees in the world and site of ancient Celtic rituals.

Alas, no digitalis purpurea was to be found but I did discover a bedraggled  English Yew (taxus baccata.)

Interestingly, Avicenna, a Persian polymath described the use of taxus baccata as a cardiac medicine in the formulary section of  his Canon of Medicine, published in 1025.

At least one author believes this was the first known use of a calcium channel blocker. Calcium channel blockers such as amlodipine, diltiazem and verapamil are widely used  in cardiology in treating hypertension and rapid heart rhythms.

On the other hand, the seeds, leaves and bark of the yew tree have long been known to be highly poisonous: ancient Celtic warriors often chose to ingest yew tree  poison to end their lives rather than be captured alive  by Roman conquerors.

A relative of the English yew, the Pacific yew (taxus brevifolia) became known for its medicinal properties. Native Americans, for example,  felt that yew extract could impart strength, treat internal injuries and lung disease. Stimulated by these observations, American scientists discovered that the bark of  the Pacific yew contained a toxic ingredient that worked  at a cellular level to inhibit the progress of some cancers.

This chemical, named paclitaxel or Taxol is now used to treat certain types of breast, lung and ovarian cancers.

The Yew’s Role in Cardiology

What, you might ask, does any of this have to do with current cardiology?

Fortunately, there is a connection because paclitaxel also plays a pivotal role in interventional cardiology.

Beginning in the 1980s cardiologists figured out how to open tightly blocked coronary arteries using catheter-based balloons. Subsequent work led to the development of stents which worked as scaffolds to keep the arteries from collapsing after expansion. However, scar tissue growth on these early stents (now called bare metal stents) often led to recurrent narrowing of the coronary arteries, limiting their long term effectiveness.

Taxus_stent_FDAThe problem of recurrent narrowing or restenosis of the stents led to the development of coronary stents that were coated with agents that worked against the tissue lining the artery forming scar.

Taxol is now used in these drug-eluting stents and has proven successful at preventing restenosis.

Boston Scientific markets their stent as the TAXUS™ Liberté™ Paclitaxel-Eluting Coronary Stent System in a direct reference to the yew tree.

As a result,  I like to say that the yew  is responsible for death and Taxus, the two things in life, according to Benjamin Franklin,  of which we can be certain.

Apologies,

-ACP

 

 

The Widowmaker Documentary: A Need For Heroes and Villains Detracts From The Truth

The documentary, The Widowmaker (available on Netflix streaming)  should definitely be watched by everyone.

It presents some great information on dying suddenly from heart attacks in an entertaining way.

It makes two important points: coronary stents don’t prevent heart attacks and coronary scans can identify advanced coronary artery disease before heart attacks happen.

I am in total agreement with these two points and have made them several times in previous posts (here and here).

The film is a work of advocacy, however, and twists the truth to prove its underlying theory: that greedy doctors and hospitals are choosing to “push” expensive coronary stents that do no good until you are having a heart attack. Also, that doctors and hospitals are also somehow suppressing the use of coronary calcium scans, which could prevent millions of heart attacks and deaths.

Creating black and white heroes and villains in documentaries makes for riveting entertainment, but often at the cost of sacrificing the truth.

Let’s look at the  villains that The Widowmaker presents.

First up is Julio Palmatz. Dr. Palmatz is a vascular radiologist who invented, along with Dr. Shatz, one of the three primary stents that ultimately gained widespread clinical usage. The Widowmaker implies that Palmatz was THE stent developer, and follows Julio as he revisits the garage in Texas where he developed prototypes for the slotted tube stent.

At this point in the movie, it would be understandable if you thought Julio was going to be one of the heroes. He seems very personable as he describes the inspiration for his stent design and points out the area in the garage where his work bench stood.

However, the documentary wants, ultimately, to portray Palmatz as greedy, unconcerned about patient welfare, and in the pocket of wealthy investors.

He has done well financially because the patent on his coronary stent was eventually sold to Johnson and Johnson for millions (and he is interviewed on the grounds of his Napa Valley vineyard).

A recent scholarly analysis of the process of the development of stents differs with this portrayal of Palmatz:

“We found that the first coronary artery stents emerged from three teams: Julio Palmaz and Richard Schatz, Cesare Gianturco and Gary Roubin, and Ulrich Sigwart. First, these individual physician-inventors saw the need for coronary artery stents in their clinical practice. In response, they developed prototypes with the support of academic medical centers leading to early validation studies. Larger companies entered afterwards with engineering support. Patents became paramount once the technology diffused. The case of coronary stents suggests that innovation policy should focus on supporting early physician-inventors at academic centers.”

Although stents ultimately have become over-utilized, they represent a tremendous invention and contribution to cardiac care.

In the setting of acute heart attacks, stents are clearly life saving and thousands of patients have had their clinical angina or claudication greatly relieved when stents are utilized appropriately for blocked coronary and peripheral arteries.

Consequently, Palmatz and many of the other interventional cardiologists who developed and performed early studies on coronary stents are widely considered heroes by the vast majority of knowledgeable cardiologists.

There is no evidence that they have colluded with industry to inappropriately promote stents or to suppress utilization of methods for early diagnosis and prevention of coronary artery disease.

The documentary then switches to characterizing the world of cardiology after stents were approved by the FDA in the early 90s.

There clearly was (and is) an irrational exuberance about stents and some of this sprang from excellent reimbursement for doing the procedures.

The focus moves to Mt. Sinai Hospital in Manhattan, and arguably the busiest interventional cardiologist in the world, Samir Sharmin.

The movie implies that Mt. Sinai was going broke until it began performing lots of catheterization and stent procedures. Sharmin who does over 1500 interventions per year and apparently earns over 3 million dollars per year is interviewed and filmed performing a stent procedure.

The average viewer likely gathers from the context of the interview with Sharmin, that he is only doing these procedures to make money.

At various points during the movie, Dr. Steven Nissen, past president of the American College of Cardiology, is interviewed and referred to as “America’s top cardiologist.”

In my opinion, Nissen has been an outstanding, independent voice of reason in the world of cardiology. During the interview, he makes the very valid points that coronary calcium scans have not been embraced for routine usage because there are no outcomes data.

At one point he says, “I don’t like medical cults” in reference to those who support more widespread coronary calcium scans.

The movie leaves the uninformed viewer thinking that Nissen is part of a cabal blocking coronary calcium scans, perhaps due to his connections with industry or an inappropriate resentment of the “calcium club” pushing the scans.

Nothing could be further from the truth. I think Nissen is one of the few prominent cardiologists who are not subject to major bias of one type or another and I strongly respect his opinions.

The movie also attempts to portray the editor of Circulation, a major cardiology journal supported by the American Heart Association as inappropriately withdrawing a paper that would have endorsed coronary calcium scanning. It’s not possible to really tell what the truth is about this withdrawal, but this is a very minor episode in the history of coronary calcium scanning.

Ultimately, The Widowmaker fails its audience in presenting the truth because it desperately wants to convince us that there is a connection between the promotion of coronary stents and the failure of coronary calcium scans to be accepted by guidelines and covered by insurance.

There is no such connection. Many interventional cardiologists are enthusiastic promoters of prevention and aggressive use of coronary calcium scans. I have seen no evidence of greedy interventionists trying to  suppress coronary scans.

In Part II of this analysis, I will take a look at the “heroes” of The Widowmaker, the inventors and promoters of coronary calcium scans, and we will see if they are truly heroic.