Cardiology in 2013: Like A Wrecking Ball
Larry HustenNews - Dec. 28, 2013
First published on Cardiobrief.org
Perhaps I’m being overdramatic but I think the best metaphor for the year in cardiology is Miley Cyrus on the wrecking ball.
The Guidelines Wrecking Ball: Like Hannah Montana guidelines are supposed to be boring and reliable.
But in 2013 the guidelines were more like Miley Cyrus. Like a wrecking ball, the NIH abandoned its long-entrenched and highly influential role in producing cholesterol and hypertension guidelines. Then the new ACC/AHA guidelines came along, abandoning tradition and targets and adopting a whole new approach. But the controversy didn’t go away. One easy prediction for 2014: we’ll see more debate about guidelines.
And then the wrecking ball metaphor may be all too apt. Bad guidelines may be deadly. Although the subject of managing cardiovascular risk before and during non-cardiac surgery seems dull and uncontroversial, it’s entirely possible that the European guideline on this topic, because it is based on tainted research, may have caused more than 10,000 deaths a year in the United Kingdom alone.
The Scientific Misconduct Wrecking Ball: Is there anything more destructive than serious scientific and medical misconduct? Unfortunately, 2013 was a banner year for bad behavior:
Japan: Following initial allegations of misconduct in 2012, in 2013 it seemed like the entire Japanese research program with the Novartis blockbuster hypertension drug Diovan was discredited. The European Heart Journal retracted the main results of the Kyoto Heart Study, the Lancet retracted the Jikei Heart Study, Novartis acknowledged that its employees participated in ostensibly “independent” clinical trials without disclosing their role in the company, and the Japanese government undertook a broader investigation.
Italy: More than a year ago nine Italian Cardiologists were arrested as part of a broad investigation into research fraud and misconduct. Due to the inefficiencies of the Italian legal system the full extent of the investigation is still unknown, but astute readers of this blog identified a wide variety of errors and discrepancies in published research by the group in Modena, including papers published in Heart, the American Journal of Cardiology, and Circulation:Cardiovascular Interventions.
Stem Cells Under Attack: To date stem cell research has generated far more hype than concrete results. Last summer, one sharp critic, UK maverick cardiologist/professor Darrell Francis, pointed out severe flaws in research from two prominent stem cell research groups:
- In July, a successful €23 million initial public offering (IPO) appeared to be based on highly questionable research. As I reported at the time, Francis and his colleagues uncovered numerous errors and discrepancies in a paper published in the Journal of the American College of Cardiology. (Francis’s letter, along with the authors’ response, has now been published in JACC.)
- In a paper published in the International Journal of Cardiology Francis and colleagues identify more than 200 errors in 48 papers from the research group of Bodo-Eckehard Strauer.
As I wrote at the time about the Strauer case, “the revelation of such widespread misconduct may lead to broader disturbing questions about the reliability of scientific publications and the ability of the clinical research system to police itself.” However, it does not appear that the cardiology research establishment has any interest in vigorously following up on any of the above cases of misconduct.
And then there was plenty of plain old fraud and greed. A New York area cardiologist received a 6 and 1/2 year sentence after admitting to $19 million in fraud. A 79-year-old Florida cardiologist was sentenced to 7 years in prison for his participation in Fen-Phen fraud. And a Louisiana interventional cardiologist is now serving a 10-year sentence for Medicare fraud.
Watching the Watchman: The Watchman device, Boston Scientific’s left atrial appendage closure device for the prevention of stroke in atrial fibrillation patients, was the source of much drama in 2013. Earlier this year a scandal broke out when the American College of Cardiology cancelled a prestigious late-breaking clinical trial presentation of the PREVAIL trial after the company broke an embargo by giving trial results to investors. Then, in December, the FDA’s Circulatory System Devices Panel recommended the device get US approval, though the committee expressed numerous reservations and concerns, suggesting that the expected approval of the device in 2014 may come with a restrictive label.
It was a good year for the Mediterranean Diet. The PREDIMED study provided the best supporting evidence yet, though it seems unlikely if anyone will ever be able to sort out the specific role of the individual components of the Mediterranean diet, which include wine, olive oil, nuts, fish, and, of course, less tangible things like sunshine and lifestyle. The nuts component received a separate boost from the publication of an influential paper in the New England Journal of Medicine.
Avandia Redux: In a remarkable if anticlimactic conclusion to a long-running drama, in November the FDA lifted major restrictions on rosiglitazone (Avandia, GlaxoSmithKline). The drug had been the subject of intense criticism and controversy since the 2007 publication of the famous Nissen meta-analsysis. Earlier in the year, in June, after a two day meeting, FDA advisors recommended that the severe restrictions (REMS) placed on Avandia be modified. The vote constitutes a modest revival in fortune for the embattled drug and its maker after many years of controversy and bad news. But it seems unlikely that the action will result in a significant revival in sales of the former blockbuster.
There’s nothing really new under the sun. A study this year found that mummies were as likely as people today to get atherosclerosis. And, somehow reminiscent of the return of the mummy, the main results of the PRAISE trial were published in 2013 only 13 years after their initial presentation.
A Good TASTE of the Future: One of the few bright points of the year was the TASTE trial, presented at the ESC and published in NEJM. The Scandananavian study will likely influence the treatment of heart attacks, largely ending the routine use of thrombus aspiration. But as I wrote at the time, the sweetest part of TASTE is that it utilized an entirely new model for performing a clinical trial. TASTE was a registry-based randomized clinical trial, which the paper’s editorialists said represents “a new paradigm… that can potentially release us from the circular (and expensive) trap of the randomized-versus-registry debate.” They continued: ”The TASTE investigators designed a large-scale trial to answer an important clinical question and carried it out at remarkably low cost by building on the platform of an already-existing high-quality observational registry. With this clever design, which leveraged clinical information that was already being gathered for the registry and for other preexisting databases, the investigators were able to quickly identify potential participants, to enroll thousands of patients in little time…, to avoid filling out long case-report forms, to obtain accurate follow-up with minimal effort, and to report their findings, all for less than the amount of a typical modular R01 grant…”
Burton Sobel, one of the leading cardiologists of his generation, died in May at the age of 75. Sobel played a key early role in the development of fibrinolysis and the first major biotechnology product, TPA. From his perch as the chief of cardiology at Washington University in Saint Louis and as the editor of Circulation, Sobel helped set the agenda for cardiology.
TheHeart.Org lost its separate identity and became absorbed into the Borg (a.k.a Medscape/WebMD). There’s still plenty of good content and news coverage, but now you have to wade through ever-increasing amounts of promotional material and, perhaps even worse, ostensibly non-commercial CME content. (A recent study in JAMA pointed out that Medscape/WebMD is the largest single recipient of industry funding among medical communication companies.)
Stents, Stents, Stents: Once again, stents provoked all sort of discussions. George W. Bush got a stent, and I wondered, along with many others, whether this was a good decision, but the truth is that in the absence of more details it was impossible to know. Some believe the ensuing debate was unseemly. I think it served a good purpose, at the very least raising the issue and offering a basis for further discussion.
A meta-analsysis in JAMA Internal Medicine found that stents were no better than medical therapy in patients with stable coronary disease and documented ischemia. Although meta-analyses need to be treated with caution, the study raised a really important and fundamental question. The findings “suggest that myocardial ischemia may be more of a marker for atherosclerotic burden” and that “the relationship between ischemia and mortality is not altered or ameliorated” by a stent in a blocked artery. Stents don’t prevent future clinical events because these are most often due to “new plaque ruptures in distant coronary segments without flow-limiting stenoses.” Unfortunately, write the authors, ”this ischemia-driven approach to PCI is a cornerstone of daily practice in the evaluation of patients with chest pain or known CAD—endorsed by the American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines.” Perhaps more guidelines will see the wrecking ball in 2014?