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October 27, 2006 -- 5:19pm ET Stent Wars Across the Atlantic: USA vs.
Europe For background on the issue, read Angioplasty.Org's report on September's European Society of Cardiology meeting in Barcelona. Basically several independent European analyses warned that potentially fatal blood clots caused by the stents (late stent thrombosis) occurred more frequently than previously reported, and that the effect persisted for years after implantation. These reports and subsequent media coverage caused what Dr. Marty Leon, Director of the TCT, referred to as "the declining state of DES" (as well as the declining sales and stock prices of several companies). So a little after "High Noon" on Tuesday, October 24 over a thousand doctors, analysts, company reps, chief executives, and 78 (count'em) reporters gathered to watch what would happen on Main Street. First the three European docs gave their presentations -- virtually the same ones they had given in Barcelona. Then TCT course directors, Drs. Marty Leon and Gregg Stone, presented two new sets of results: new analyses of the raw unpublished data from the original nine randomized clinical trials used to gain approval for both Cypher and Taxus drug-eluting stents. Turns out that immediately following the Barcelona "firestorm", the stent manufacturers had given them the raw "patient-level" data from these clinical trials -- data that the same companies had previously declined to provide, for example, to one of the European presenters, Dr. Matthias Briel of Basel, Switzerland. Adding to the mix, these new analyses also used a new definition of stent thrombosis . With "rawer" data and new definitions, the results of the U.S. analysis were quite different from the European. The conclusions, as stated in the front page headline of the following morning's TCT Daily: "Cypher/Taxus: No Increase in Thrombosis". Then, one hour into the session, Marty Leon advanced to the microphone, metaphorically pulled off his surgical glove and tossed it down from the podium onto the floor in front of the panelists:
The Europeans had been served. Will you retract, sir?! Dr. Camenzind countered:
Typing errors?? Slide errors?? Was Dr. Camenzind actually postulating that the published results used to obtain approval of the Cypher and Taxus stents might differ from the raw data because of a faulty PowerPoint presentation? Certainly, he was exploring the possibility that the published reports of the raw data might be mis-stating the raw data itself. Touché! If you are lost here, so were many in the audience and on the panel (Dr. Sigmund Silber of Munich stated that the various results were "totally confusing".) A significant point: all the data in question above are from the nine clinical trials that were used to gain approval for the Cypher (RAVEL, SIRIUS, E-SIRIUS and C-SIRIUS) and Taxus stents (TAXUS II, TAXUS II, TAXUS IV, TAXUS V and TAXUS VI). The patients in these trials were done for "on-label" indications, meaning relatively straight-forward blockages, stable patients, expert cardiologists doing the procedures. And the dispute between the U.S. researchers and Dr. Camenzind centered on analysis of the data, source of the data and integrity of the data. But another and much larger issue was also surfaced in the other European studies. In the "real world", much stenting is done "off-label" -- sicker patients, more emergency situations, more complex multivessel disease, multiple stents. None of the patients included in these original clinical trials fit these definitions and it is in this "off-label" population that the European studies found even higher rates of stent thrombosis. In the final minute of the meeting, Marty Leon deftly swiveled his attention from stage right to stage left and challenged Bram Zuckerman of the FDA:
Mr. Zuckerman quickly retorted:
Not extrapolatable to the "real world", so-called or not -- this is the crux of the problem: that the "readjuticated" data at the center of today's dispute may not be that relevant to current day-to-day practice, no matter which side of the Atlantic the analysis is done on. Reinterpreting the relatively tame cases done for the initial safety and efficacy studies is one thing. But trying to determine just what the extent of the problem is in the real world is another. And even the FDA agrees that a source of strong clear data for that determination is not immediately obvious. I'll deal with these issues in a future post (as will the FDA -- they have called for a large public meeting on December 7-8 about these issues). As for the post-approval data not being made public, as we were leaving the auditorium, I asked Boston Scientific's Chief Medical Officer, Dr. Donald Baim, if that was true -- if the company has kept the post-market registry results hidden? He said, "absolutely not -- they've got our data. Just look at ARRIVE I and ARRIVE II." No one doubts that late stent thrombosis in DES exists. Even Boston Scientific issued a press release confirming it. The question is whether it is as significant as the European studies suggest, whether it is offset by reduced restenosis, and mostly, what it means for patients. « permalink » « send comment » « back to top » October 23, 2006 -- 11:15pm ET Drug-Eluting Stents: The Very Hot Topic
at the TCT Even Boston Scientific, who had previously admitted that their Taxus drug-eluting stent (DES) had a slight but statistically significant increase in stent thrombosis over bare metal stents, presented a study which claimed that the competing Cypher stent had the same problem. Am I supposed to be comforted by this? The thousands of cardiologists assembled here in Washington are all anticipating tomorrow afternoon's panel discussion of the European Congress of Cardiology (ESC) data that started all this concern over thrombosis. The program bills it as the "Stent Thrombosis Hot Line Session". Part One is titled "The ESC Firestorm". So imagine everyone's surprise when tonight, in the middle of Boston Scientific's evening symposium in the Grand Ballroom of the Renaissance Washington hotel, the fire alarm sounded, the red trucks arrived and the entire hotel had to be evacuated. The presentation was titled: "The Next Generation DES: Are We There Yet? Are we there yet? Are we there yet? Are we there yet? « permalink » « send comment » « back to top » October 18, 2006 -- 10:10pm ET Team SPIRIT** Today, both companies posted a profit in their quarterly reports: Abbott's rose 5% compared with the third quarter from last year; Boston Scientific's report was even better, showing a profit of $76 million in third quarter 2006, compared with a net loss of $269 million for the same period last year, even though the sales of Boston's Taxus drug-eluting stent are declining slightly due to safety concerns with the current generation of these devices. And on Monday, a new West Virginia start-up device company, Paragon Intellectual Properties, announced $15 million in financing, including a new R&D center in California. The infusion of capital came from local private investment, and two major device manufacturers, unnamed in the press release -- but they are indeed...the Team: Abbott and Boston Scientific. Is there a pattern here? ** couldn't resist the pun -- SPIRIT is the name of the clinical trial series validating the Xience/Promus stent. « permalink » « send comment » « back to top » October 13, 2006 -- 2:06pm Note to Reporters: Attribute Your Sources,
Especially When They're Me! A month ago, Arlene Weintraub of BusinessWeek requested an interview with me. She was writing an article on the upcoming Transcatheter Cardiovascular Therapeutics (TCT) conference and had read my scintillating commentary from last year's meeting . So naturally she wanted to talk to me. With great hesitation I agreed, mainly to gain some publicity for our website, Angioplasty.Org. I told myself to be very careful, because, as I have opined in the past, "...the media's thirst for a sexy (or death-y) headline will not go unquenched! " She went with death-y. Her article "Medicine In Conflict " appeared online yesterday (co-authored by Amy Barrett) and by the second paragraph, she had already zeroed in on the unfortunate death of a patient two years ago during the TCT. The patient was being given a new aortic valve, percutaneously -- that is, via catheter instead of via open surgery. The valve, BusinessWeek points out, was manufactured by a company co-founded by Dr. Martin Leon, the Director of the TCT. The procedure was televised "live" from Milan, where Dr. Antonio Colombo, one of the pioneers in interventional cardiology, was attempting to perform this very new procedure. The patient developed serious problems and the broadcast was ended. It was later announced that the patient had expired -- the second time this had occurred in over 500 cases done since the TCT began. The implication in the BW article, of course, was that Dr. Leon was using the TCT to publicize a device he would profit from. The BusinessWeek article states:
The question also borders on being uninformed. The fact is that the 77-year-old patient who died was very sick and frail to begin with. Had the BusinessWeek reporter understood anything about the protocol for performing these types of experimental interventional procedures, she would have realized that this patient had already been rejected for surgery -- his chances of surviving an open surgical procedure were nil. The percutaneous aortic valve was the only alternative to his slowly and painfully wasting away. Also, had the reporter read the summary of the case published in theheart.org (September 28, 2004), she would have discovered what the autopsy revealed: that the aortic valve had been placed perfectly, but that the very sick patient died of heart failure -- his heart wouldn't have survived standard surgery and unfortunately it didn't tolerate this minimally invasive procedure either. Considering the feeble state of the patient, for Dr. Leon to have used this case to promote his device, he would have to be considered a very poor businessman, which he most definitely is not! As for me, when I was asked during the interview for interesting or out-of-the-ordinary events that I had seen at the TCT, I related the surrealistic atherectomy of the opera singer from La Scala. (I happen to have a rare copy of that broadcast from Milan -- Marty Leon gave it to me for a video I was producing and John Abele, co-founder of Boston Scientific, showed my copy at TedMed as an example of innovative medical communications.) Ms. Weintraub writes:
It was a bizarrely entertaining moment, fully participated in by physician, patient and accompanist (in scrubs) to the crowd's delight. The only problem is that Ms. Weintraub failed to attribute the story to me (at least in the online version). I spent almost an hour on the phone with the reporter, carefully parsing my words so that my observations about medicine, money and devices would not be misquoted. The good news for me was that I wasn't misquoted; the bad news was that I wasn't quoted at all. I'm not going to talk here about the TCT and whether or not the large sums of money flying around the Washington Convention Center in less than two weeks have any untoward effect on healthcare and patients. But I can strongly urge readers to view the epilogue of my 1997 documentary, "PTCA: A History" (RealVideo Player required) in which the pioneers of angioplasty specifically discuss the conflicts inherent with marketing and physician-entrepeneurs. And it's not an either-or issue. Doctors can be inventors. Inventions need capital to be developed. Rights, patents, inventorship, venture capital, speaker fees, stock options all figure into a complex mix which can be abused. Many of the issues raised by Ms. Weintraub in the BusinessWeek article are very valid and very important -- and they are issues that we have been concerned with for years. Has the field of interventional cardiology been oversold? Are too many procedures being done? Cardiologists have answered this question for themselves. In a recent unscientific poll, 71% said that percutaneous coronary interventions are "grossly overused". On the other hand, in a study by the journal Health Affairs, balloon angioplasty was named the 3rd most important medical innovation since 1975. So the issues are not as simplistic and certainly not as clandestine as BusinessWeek suggests. If you attend the TCT (or any of the major heart meetings held throughout the world) the scent of capitalism is right out front. The physicians are standing in front of what vascular surgeon Sir Peter R. F. Bell described to me as "a tidal wave of dollars". I also would direct readers to an article about the TCT that appeared in the New York Times 8 years ago. That piece, entitled "Where Marketing and Medicine Meet" (in contrast to BusinessWeek's "Medicine in Conflict") was written by Gina Kolata and I feel gave a picture of what the TCT meeting is like that is much more accurate. It would have to be more accurate. The BusinessWeek reporter told me she had never attended a TCT meeting and so was trying to get the flavor of it by talking to people like myself. So glad to be of service. Next time, tell 'em Burt sent you.... « permalink » « send comment » « back to top » October 3, 2006 -- 9:18pm ET "Elective" Procedures: Current
Voting Trends They've also stated that they have not seen any indication in their sales figures of a significant switchover back to the bare metal variety. But stent sales figures for this past quarter and the results of three polls paint a different picture. First off, an AP story today, subtitled "Analyst Rethinks Ratings Given Heightened Blood Clot Concerns on Drug-Coated Stents", reports that Merrill Lynch posed questions about drug-coated stent safety to 50 "heart surgeons" (we believe the AP writer meant "interventional cardiologists" -- cardiac surgeons would rather not think about stents at all, a device which has eroded bypass surgery to less than 1/3 of all procedures). The responses were as follows:
AP didn't report what the other 28% felt -- we'll assume they are not changing their current practice. (Note: the 2% who will completely stop represents a single doctor.) Certainly doesn't look like a growth market, and Merrill downgraded Boston Scientific which derives significant percentage of its income from drug-eluting stents. Johnson & Johnson was not downgraded -- it's a bigger company and Cordis is just one division Another poll currently being conducted on the professional cardiology site CRTonline asked its members what their current understanding of the DES thrombosis data was, and after the first two days (less than 100 total votes), the rough results were:
The messaging that DES and BMS are pretty much the same in terms of late stent thrombosis seems to have little traction. In fact, Boston Scientific revealed last month that their internal data review showed a slightly higher rate for the Taxus, when compared to bare metal stents. The third poll was taken on theheart.org, another professionals-only site. Here, doctors were asked if they thought angioplasty and stenting were "grossly overused" in treating patients with stable angina, and here the results of over 1100 voters were pretty striking:
Now these are unscientific surveys, two of them with very small numbers. But add to the mood glimpsed in these polls the fact that special sessions on Late Stent Thrombosis have quickly been organized at upcoming national interventional meetings. Lenox Hill's NY-ACE meeting is next week and, as the first major U.S. meeting since the European Society of Cardiology (ESC) congress in Barcelona where all this recent thrombosis talk started, is sure to be host to some interesting discussions. And two weeks later, a just-added special session has been announced for the Transcatheter Cardiovascular Therapeutics (TCT) meeting in Washington. The hour-long session includes a "Roundtable Discussion with physician scientists, industry and FDA" and is titled the "Stent Thrombosis Hot Line" which will address the "ESC Firestorm" -- do I feel the temperature rising? « permalink » « send comment » « back to top » October 1, 2006 -- 6:00pm ET Relaunches and Recalls On Angioplasty.Org we've created an entirely new section on the site dealing with Imaging and Diagnosis -- CT angiography, MRA, stress tests, catheterization, etc. Within a couple weeks of its appearance, it has become one of the most popular sections on the site. Patients are interested in getting the latest information on new imaging technologies. The section is supported by a grant from Toshiba America Medical Systems. Our readership was also boosted by two major news scare-cycles, the first being the CHARISMA trial results back in March -- when misleading headlines appeared in major newspapers, like "Plavix and aspirin combo can be deadly", patients flocked to the net to find out the real story. They found it here. Except for those unfortunates who didn't find our Patient Advisory and stopped their Plavix and had heart attacks. Yes, it's true. The news can kill you. The second set of dreadlines occurred just a few weeks ago when the World Congress of Cardiology meeting in Barcelona heard reports from European centers about increased late stent thrombosis and raised mortality rates in patients who got drug-eluting stents. Again, we posted a Patient Advisory to clarify the headlines. (And we'll be writing about this situation more in the coming days.) With each incident of "press stress", our readership increased. We sort of wished this didn't have to be the way to a wider audience, but Angioplasty.Org seems to be one of the few places on the Web that provides this kind of up-to-date information that can clarify for patients and others the implications of new studies being reported in the mainstream media. So the stent blog is relaunched. As for the recalls... ...it's beginning to look like "recall" may be recalled. The Heart Rhythm Society released its recommendations last week regarding the tracking and reporting of medical device problems and one of its points was that the term "recall" was misleading to patients. The panel felt that when patients hear that their defibrillators have been "recalled", they assume they need to go into the hospital and have a surgical procedure to remove it and replace it with a new part, kind of like the potentially defective gas tank on my minivan (really, only one of them actually ever blew up...). But it doesn't quite work that way. There is a margin of error, a statistical probability of a complication from the required surgery that may in fact be higher than the chances of the device being harmful. So the Society is suggesting using the terms "advisory notice" or "safety alert" so as not to unnecessarily panic patients. So, don't panic. Please. Doesn't that make you feel better? |