This was a really grim year for anyone who thought we had things pretty well figured out. Time and again conventional wisdom was thrown out the window. 2012 forced the cardiology community to reconsider what it thought it knew about HDL cholesterol, platelet function tests, aspirin resistance, triple therapy, IABP, and more.
One device company, with a lot of help, did just about everything right when it introduced a radical, highly disruptive new technology. Another device company did just about everything wrong in handling a series of crises. The new generation oral anticoagulants continued to make gains– slowly– but also failed to achieve the early blockbuster success that some had thought they might achieve.
And it was another bad year for scientific integrity.
Conventional Wisdom Isn’t
Raising HDL cholesterol had to be great. Then the evidence arrived. Just last week HPS2-THRIVE put the final nail in the niacin coffin. (I wonder what all the critics of AIM-HIGH have to say now?) And another CETP inhibitor bit the dust. The HDL hypothesis is far from dead, but any claim of benefit due to raising HDL will need to be rigorously demonstrated in a large, well-designed clinical trial.
Platelet function tests just had to be useful in guiding therapy. Then ARCTIC came along and blew a cold wind on the idea.
On a related note, many believed that testing for aspirin resistance might be a good idea. Then a paper in Circulation presented strong evidence that the entire concept of aspirin resistance might be a myth.
Triple therapy for PCI patients already receiving anticoagulation was standard clinical practice, endorsed by the guidelines. Now, after WOEST, we know that what we knew was wrong. Drop the aspirin.
Intraaortic balloon counterpulsation (IABP) has a class 1 recommendation for patients in cardiogenic shock following myocardial infarction for whom early revascularization is planned. Until IABP-SHOCK II was presented at the ESC and published in NEJM.
Depending on your perspective the FREEDOM trial either confirmed or denied conventional wisdom. We now know with near certainty that diabetics with multivessel disease have better outcomes with CABG than with PCI. An important lesson from an important trial.
Conventional wisdom had it that chelation therapy was worthless. The conventional wisdom may still be valid, but the NIH’s TACT trial means the debate will continue. It’s hard to imagine a satisfactory result to this controversy, despite the good intentions of the NIH and at least some of the TACT investigators. In general I support the concept of testing alternative therapies, especially if they gain traction in clinical practice, but it’s not clear yet whether we really learned anything from TACT (except that doing trials like this is extraordinarily hard). A trial like TACT should only be performed if it has a good chance of actually answering the big clinical question. Unfortunately, TACT didn’t do this.
TAVR: Bright Spot in a Dark Year
The 2011 FDA approval of transcatheter aortic valve replacement (TAVR) was monumental. This year all the key players– Edwards Lifesciences, the cardiology and surgery medical societies, CMS, and the FDA– continued to behave in an exemplary fashion, once again setting a model for the rest of the medical world about how to introduce a radical new technology without causing harm from either of the polar dangers of overuse or underuse. In the first half of the year, the ACC, AATS, SCAI, and STS, in conjunction with several other medical organizations, released critical consensus documents to guide uptake of TAVR and defining criteria for TAVR programs and operators. These documents were largely accepted by CMS when it issued a National Coverage Decision for TAVR. Later in the year the FDA extended the indication for TAVR to include high risk patients who were eligible for surgery.
TAVR strikes me as a good example of how the FDA usually gets things more or less right. The situation in Europe is quite different, according to researchers in Belgium, who claim that 40,000 patients in Europe received the device before there was any good evidence demonstrating benefit. Some conservative US critics prefer the European system to the US system (an irony in itself) and think TAVR should have been approved and widely adopted in the US long ago. I couldn’t disagree more.
Reality Distortion Field at St. Jude
St. Jude had a tough year. The Riata lead problem delivered a major blow to the company’s ICD portfolio, and the company struggled desperately to prevent spillover to the company’s Durata leads. Instead of getting ahead of the news and taking a proactive position, thereby demonstrating to its core electrophysiologist customers that it was doing everything possible to fully understand and address the problem with its leads, the company consistently ignored or downplayed the cascade of bad news. It was almost as if St. Jude was trying to teach cardiologists that they shouldn’t believe anything the company says. The company even went so far as to request a retraction of an article that raised questions about Riata in Heart Rhythm by Robert Hauser, a distinguished electrophysiologist. The request was summarily denied by the journal’s editor, Douglas Zipes, one of the true pioneers of the entire field of electrophysiology.
Then, in its handling of the RESPECT trial of PFO closure, the company transformed the ideals of research and development into research and denial. Although the trial missed its primary endpoint, you wouldn’t know it from the company’s public statements. First, during an earnings call that took place well before the trial had been first presented, St. Jude CEO Dan Starks gave a preview of the RESPECT results: “we are optimistic that these will be favorable results.” Then, after the trial was presented, the company doubled down on its defensive position and issued a press release stating that the trial “provides clinical evidence of risk reduction” and offers “compelling evidence” for use of the St. Jude device “over conventional medical management alone.”
I think the company would be better served by acting as if it existed in the real world instead of an alternate reality where everything works according to plan. Stuff happens. The company should deal with it. It shouldn’t fight with researchers and clinicians, and it shouldn’t try to cram its views down peoples’ throats. They don’t like the taste.
Apixaban: Always A Bridesmaid
The development and entry into the marketplace of the new generation of oral anticoagulants has been the most eagerly anticipated and watched event of the past several years in the cardiovascular community. Though apixaban (Eliquis, Pfizer and Bristol Myers Squibb) is thought by some to have the best profile of the new drugs, it’s been plagued by delays at the FDA and by year’s end still remained without any FDA approved indication in the US. The FDA will decide the fate of the AF prevention indication by March 17, 2013. Some observers think the FDA may act much sooner than that.
In other developments that helped to curb enthusiasm for the new anticoagulants, the FDA rejected an ACS indication for rivaroxaban (Xarelto, Johnson & Johnson) and the FDA added a contraindication to the label for dabigatran (Pradaxa, Boehringer Ingelheim) against use of the drug in patients with mechanical valves.
I remain convinced that the new oral anticoagulants represent a great advance, but it’s also clear that they are not miracle drugs and need to be used with care and caution.
Biting the Generic Dust
In any other year the transition of clopidogrel (Plavix) to generic status would have been viewed as a seismic event. After all, Plavix was for many years the second-best-selling drug in the world. But coming just six months after the same thing happened to atorvastatin, the best-selling drug of all time, the event just didn’t seem that unusual or remarkable.
Also this year, valsartan (Diovan) went off patent, but it took a while for a generic version to appear.
Fraud, Plagiarism, and Scientific Misconduct
Unfortunately it was a good year once again for scientific misconduct and other shenanigans.
Italy lays claim to the dubious honor of hosting the worst scandal of the year. Nine Italian cardiologists, including Maria Grazia Modena, the chief of cardiology at Modena Hospital and a former president of the Italian Society of Cardiology, were arrested as part of a broad investigation into serious medical misconduct at Modena Hospital. The investigation encompasses at least 67 other individuals and a dozen medical equipment companies, including 6 foreign companies. The charges include conspiracy, fraud, embezzlement, bribery, forgery and performing unauthorized clinical trials. Several news reports mentioned that stents and angioplasty balloons were involved.
The case of the Dutch researcher Don Poldermans raises troubling questions about the quality of studies coming out of research factories like Poldermans’ group at the Erasmus Medical Center.
University of Connecticut resveratrol researcher Dipak Das was accused of serious scientific misconduct, leading to the end of his career and multiple journal retractions.
The Korean Circulation Journal retracted an article on the J curve in hypertension because it heavily plagiarized a similar article in JACC.
As he told me earlier this year, Mark Midei can’t get a job taking blood pressure at a Walmart, but if misery loves company then perhaps he has found some comfort this year.