November 23rd, 2011
CardioMEMS CHAMPION Trial Undergoes Scrutiny From Wall Street Ahead of Next Month’s FDA Panel
Larry Husten, PHD
Note to readers: An earlier version of this story stated that the FDA may be concerned about the conduct of the CHAMPION trial. This statement could be construed as an implication of ethical misconduct or negligence on the part of the trial sponsors or investigators. I apologize if I conveyed this impression in the earlier story. This story has been further updated below, as indicated in the text.
Next month’s meeting of the FDA’s Circulatory System Devices Panel has stirred controversy, though it may be a tempest in a teapot. On December 8 the committee is scheduled to review the PMA for the implantable CardioMEMS HF Pressure Measurement System (HF System), which provides daily pulmonary arterial pressure measurements for the purpose of guiding heart failure treatment. The potential controversy involves the possible unblinding of patients during the pivotal CHAMPION trial. (Note: The earlier version of this story stated that concerns had been raised about the unblinding of the trial investigators. As the trial publication clearly states, CHAMPION was a single-blind trial in which only the patients but not the investigators were blinded to their treatment assignment.)
On Wednesday morning Wells Fargo analyst Larry Biegelsen reported that
…the FDA has recently visited a number of sites that participated in the CardioMEMS pivotal trial because the FDA has concerns with how the trial was conducted. It is our understanding that FDA is concerned that physicians in the study may have been coached on how to treat the patients in the treatment group and this may have led to bias in the study.
Here is the relevant text from the Lancet publication of the trial:
To maintain patient masking, all patients were asked to take pressure readings every day. Standardised clinician communication scripts were provided for telephone calls to patients about changes to drugs. Sites were required to balance the number of contacts between patients in the treatment and control groups. Patients were masked to their assignment group. The masking of patients was maintained until analysis of the 6-month data was complete for the entire patient population.
According to Biegelsen, however,
Both groups of patients (the treatment and control groups) received calls from physicians so that the frequency of contact with patients was similar between the 2 groups. To ensure that physicians did not inadvertently disclose the patient’s randomization assignment, standardized clinician communication scripts were provided for use during patient contact. However, we were told that the conversations were very different with each patient group because physicians were forced to call patients in the control group for no reason other than to maintain a balance in the number of calls to each group.
Biegelsen reports that trial investigators have said that this does not represent a serious criticism of the trial, and notes that the FDA had signed off on the trial protocol.
Update: Senior management at CardioMEMS has assured me that they are not aware of any extraordinary problems associated with the blinding process in CHAMPION. Although difficulties in trial design and blinding often occur in device trials, CardioMEMS management is not aware of any serious problems that occurred in this area in the trial. The protocol and blinding process was worked out in details with the FDA and the steering committee. CardioMEMS also stated that it believes the FDA has only been conducting routine site audits and that the company is unaware of any serious problems associated with these audits.
Here is the description in the trial protocol of the procedures for handling phone contacts with trial subjects:
A matching phone contact will be generated to a CONTROL group subject when a contact is made to a TREATMENT group subject. The script for both contacts will be identical with the exception of the medication adjustment made to the TREATMENT group subject.
Script
TREATMENT group:
“Hello, (insert subject’s name), this is (insert clinician’s or coordinator’s name) from (insert institution). Thank you for taking your HF pressure measurements. At this time, we would like you to (insert treatment plan, i.e., increase lasix to 40 mg bid, etc.). Please continue to take your daily HF pressure measurements. Thank you.”
CONTROL group:
“Hello, (insert subject’s name), this is (insert clinician’s or coordinator’s name) from (insert institution). Thank you for taking your HF pressure measurements. At this time, we are not making any changes to your medications. Please continue to take your daily HF pressure measurements. Thank you.”
When a TREATMENT group subject is contacted, the site personnel will randomly select a subject from the CONTROL group and will contact that subject as soon as reasonably possible.
Finally, a blinding survey found that the vast majority of patients in the trial did not know the group to which they had been assigned, and there was no significant difference between the groups in correct guesses.
November 22nd, 2011
Study Examines Role of Surgery for Infective Endocarditis and Heart Failure
Larry Husten, PHD
Although current guidelines recommend valve surgery for patients with infective endocarditis and heart failure (HF), a large prospective registry finds that many of these patients do not undergo surgery — and have much worse outcomes.
In a paper published in JAMA, Todd Kiefer and colleagues report on 4166 patients with infective endocarditis enrolled in the International Collaboration on Endocarditis – Prospective Cohort Study. One third of the patients had HF, yet only 61.7% of these had valve surgery. In-hospital mortality was 29.7% for all patients with HF, but it was significantly lower in the surgical group than in the medical therapy group: 20.6% versus 44.8% (p<0.001). At 1 year, the difference in mortality was larger: 29.1% versus 58.4% (p<0.001). The investigators report that the association between surgery and survival “was apparent across the spectrum of HF severity.”
The authors write that their results support the need for “multidisciplinary, guideline-based management of infective endocarditis.”
November 22nd, 2011
Long-Term Follow-up of HPS Shows Extended Benefits of Statins
Larry Husten, PHD
Long-term follow-up of patients enrolled in the Heart Protection Study (HPS) demonstrates continued benefits in the group originally randomized to receive simvastatin instead of placebo. The main results of the HPS, published in 2002, showed a significant 23% reduction at 5.3 years in major vascular events associated with simvastatin treatment among the 20,536 patients with coronary disease enrolled in the trial.
Now the HPS investigators report the follow-up results after a mean of 11 years in a paper published online in the Lancet. After the trial ended, statin use and, consequently, LDL levels were similar between the two groups. In the first post-trial year, patients who had been randomized to simvastatin during the trial had an additional 14% reduction in events compared with patients who had been randomized to placebo (p=0.05). After the first post-trial year, there were no further additional differences between the former groups, but the relative difference between the two groups remained unchanged.
Overall during the post-trial period, there were no significant differences between the two original randomized groups: 21.7% and 22.5% of the patients originally allocated to simvastatin and placebo, respectively, had a first event (RR 0.95, CI 0.89-1.02, p=0.17). The incidence of cancer was the same in both groups: 17%. No other safety signals emerged during the 11 years.
In an accompanying comment, Payal Kohli and Christopher Cannon write that the long-term results of the HPS “suggest that the early benefit of statins is likely to be followed by a prolonged legacy period, with benefit maintained over time” and “that extended use of statins is safe with respect to possible risk of cancer and non-vascular mortality.”
November 22nd, 2011
Merck Pleads Guilty and Pays $950 Million for Illegal Promotion of Vioxx
Larry Husten, PHD
The US Department of Justice announced today that Merck, Sharp & Dohme will plead guilty to illegal promotion of Vioxx (rofecoxib) and will pay a $950 million in fines and penalties to the US government and individual states.
The criminal plea is tied to Merck’s off-label promotion of rofecoxib for rheumatoid arthritis (RA) from 1999 until 2002, since the drug did not have an indication for RA at that time. The civil settlement is tied to a broader range of allegedly illegal conduct by Merck, including statements about the cardiovascular safety of rofecoxib made by Merck representatives. The company will also enter into an expansive corporate integrity agreement with the government.
In its own press statement, Merck said that the civil portion of the settlement “does not constitute any admission by Merck of any liability or wrongdoing.” Merck also said:
As part of the plea agreement, the United States acknowledged that there was no basis for a finding of high-level management participation in the violation. The government also recognized Merck’s full cooperation with its investigation.
November 21st, 2011
Prominent Dutch Cardiovascular Researcher Fired for Scientific Misconduct
Larry Husten, PHD
UPDATE (Posted Monday, November 21): Over the weekend more details emerged about this story. An executive summary of the report from the investigative committee at Erasmus MC, dated November 16, appeared on the Erasmus website. Here is a brief summary, based on help received from Google Translate, Babel Fish, and native Dutch speakers:
As previously reported (below), the committee found “serious deficiencies” in obtaining informed consent in at least one and possibly another of the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) studies led by Poldermans (see the table below). Although some patients may have had procedures they would not have received otherwise, the committee found no evidence that any patients had been hurt by these procedures.
The committee found “several serious errors and protocol violations” in the DECREASE II and DECREASE VI studies and raised the possibility that the blind may have been broken in the DECREASE II, IV, and VI studies. For the DECREASE II and VI studies the committee determined that there was no independent endpoint evaluation. For DECREASE VI the committee found evidence of data fabrication in submitted abstracts for the study (the trial has not been published).
The committee recommended that the the DECREASE VI study be discontinued and its sponsor, Roche Diagnostics, informed about the decision. It recommended that the editors of the journal in which DECREASE II was published (The Journal of the American College of Cardiology) be told about the questions raised about informed consent in the trial, but the committee did not feel the publication needed to be retracted.
The committee found no evidence of scientific misconduct in other researchers, and noted that junior colleagues of Poldermans were in no position to challenge his authority.
The investigative committee is composed of a former dean, an emeritus professor of hematology, and an emeritus professor of hematology, all associated with Erasmus, as well as professors of cardiology and internal medicine from Leiden University Medical Center.
Here is the original story (posted Friday, November 18):
Don Poldermans, a well-known researcher in cardiovascular medicine in the Netherlands, has been fired for scientific misconduct by the Erasmus Medical Center in Rotterdam.
According to a statement from Erasmus Medical Center, an investigation found that Poldermans was
careless in collecting the data for his research. In one study it was found that he used patient data without written permission, used fictitious data and that two reports were submitted to conferences which included knowingly unreliable data.
Poldermans, according to Erasmus, has accepted the conclusions of the committee and “expressed his regret for his actions,” but said his actions were “unintentional.”
The news has been reported on the Dutch website NRC and then subsequently in English on DutchNews.NL and Retraction Watch. Erasmus Medical Center has also issued a Dutch language press release.
Poldermans had been a professor of medicine and the head of section the of perioperative cardiac care at the Erasmus Medical Center. He was widely published and active in the field, serving as a member of the ESC committee for practice guidelines and as the chairperson of the ESC guidelines on preoperative cardiac risk assessment and perioperative cardiac management in noncardiac surgery.
Poldermans was a highly prolific author and researcher. He was the first author of an influential New England Journal of Medicine paper in 1999 on the use of bisoprolol during vascular surgery and the senior author of a 2009 NEJM paper on the use of fluvastatin during vascular surgery. He was also the co-author of a 2005 NEJM editorial on beta-blockers in noncardiac surgery. He was the senior author of a 2006 paper in the Archives of Internal Medicine on the value of the ankle-brachial index, the senior author of a JACC paper in 2010 on the timing of preoperative beta-blocker therapy in vascular surgery patients, and the first author of a 2003 Circulation paper on statins in vascular surgery.
In the 2009 NEJM paper, Poldermans reported he had received “consulting fees from Medtronic, Novartis, and Merck and grant support from Novartis.”
The following is taken from a review article by Poldermans in a European Heart Journal supplement:
Summary of key findings of the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) series of studies:
DECREASE I: In high-risk patients undergoing non-cardiac surgery, perioperative beta-blockade with bisoprolol significantly reduces cardiac death and MI in the short- and long-term
DECREASE II: Patients identified as intermediate risk on the basis of a simple clinical assessment do not need pre-operative echocardiographic cardiac stress testing, provided that they receive bisoprolol to maintain resting heart rate at 60–65 b.p.m.
DECREASE III: In high-risk patients undergoing major vascular surgery, fluvastatin XL significantly reduces myocardial ischaemia and the combined endpoint of cardiovascular death and MI
DECREASE IV: In intermediate-risk patients, bisoprolol significantly reduces cardiac death and MI, with a non-significant trend towards a beneficial effect of fluvastatin XL
DECREASE V: In high-risk patients with extensive stress-induced ischaemia, coronary revascularization (added to tight heart rate control with bisoprolol) does not produce any additional reduction in death and MI and delays surgery.
In addition, DECREASE VI was testing NT-proBNP for the evaluation of cardiac risk in patients undergoing vascular surgery.
Thanks to Marilyn Mann, Ray Lau, Greta Carraway, Rick Lange, and Jacqueline Limpens for technical and linguistic support.
November 18th, 2011
AHA.11 Concludes and Our Fellows Reflect
CardioExchange Editors, Staff, Eiman Jahangir, MD, John Ryan, MD, Amit Shah, MD, MSCR and Reva Balakrishnan, MD, MPH
Several Cardiology Fellows who are attending AHA.11 this week are blogging together on CardioExchange. The Fellows include Revathi Balakrishnan, Eiman Jahangir, John Ryan (moderator), and Amit Shah. Read the previous post here. This is their final post. See their complete coverage at the bottom of this post and in this review of our AHA coverage.
Readers, were there any unique experiences or sessions at the conference that you would like to share?
Was there anything you didn’t like and wish you could change? We welcome your comments.
Reflections on My AHA experience: Choose Your Own Adventure
Revathi Balakrishnan
Although the conference is not over at the time that I write this, my first-year duties beckon me back to the reality of fellowship back home (and I’d like my co-fellows at home to not go completely insane from coverage of our call). Reflecting on the experience, I’m amazed at the wealth of knowledge that can be gained in such a short period of time. I have gained a lot through this experience, not only from attending the sessions, but also from spending time with co-fellows and faculty from my home institution, watching presentations of their research with a sense of admiration, and having some insight into the immense effort and innumerable hours that can go into a 10-minute presentation. I was able to reconnect with old friends on similar career paths, all in different stages, gleaning some sagely advice. I’ve also gained a sense of how one can eventually use this meeting to make new connections for career building.
One thing I have learned is that one attendee can have an entirely different AHA experience than another based on how one tailors it to their interests, similar to those “choose your own adventure” books from childhood (without the 16-point font and fifth-grade reading level, of course).
Here are some highlights from my conference experience:
- Late-breaking sessions: This was the place to start — same place, same time everyday — and then branch off into more specific interests from there. I had difficulty deciding on what to go to when interesting sessions were going on at the same time as the late-breaking updates, such as the clinical science special report sessions that highlighted the stem-cell therapy trials. Since we do get emails in the morning of the late-breaking slides for the day, one could review them in the morning and decide which presentations to attend.
- Amongst the sea of catchy acronyms, several trials kept the fellows talking long after the presentations were over:
1. ATLAS ACS–TIMI 51
2. Post-MI FREEE
3. PALLAS
4. SATURN
5. AIM-HIGH
- Thought-provoking small sessions and seminars; One that was particularly interesting to me:
Non-obstructive CAD: Not important?
A session moderated by Dr. Judith Hochman, with presentations of research from Dr. Harmony Reynolds, Dr. Noel Merz, Dr. Leslie Shaw, and Dr. Amir Lerman that calls into question how we approach management of angina and ACS in non-obstructive CAD; that it encompasses a complex spectrum of hidden macro- and microvascular disease and adrenergic response. An excerpt from the session:
ACS and Nonobstructive Disease in Women: Dr. Harmony Reynolds presented data on women with troponin positive ACS without obstructive CAD on cath. IVUS and cMRI were done to characterize lesions and presence of myocardial injury. Plaque rupture was found in 38% of patients with non obstructive lesions, and abnormal MRI patterns (LGE, predominantly ischemic) were found in 59% of patients. The full paper can be found here.
- What I wished I knew about beforehand: Detailed planning is key. I had a sense of what I wanted to see, but detailed planning will leave you less frustrated and overwhelmed — including planning which posters to see. Someone I know (who may or may not be a co-contributor to the fellows blog) actually had a detailed excel spreadsheet planned far in advance with dates and times of different talks they were interested in.
- The dinners: Not explicitly obvious in the programming, but seemingly valuable learning and networking experiences. One of my co-fellows went to the AHA Evening symposium on lipids and inflammation and thought it very informative and clinically relevant. A friend attended the Women in Cardiology dinner, which provided a wealth of networking opportunities with what seemed like a who’s who of female leaders in the field.
- Avoid the expo floor: Resist the temptation for freebies. There’s not much you can get for free at the booths anymore, so some have resorted to using food. My co-fellows and I were lured in by the smell of pumpkin crumble at the Pradaxa booth, and as we were waiting on line for a sample, a representative scanned our badges (which conveniently have all our information on them). It was a sneaky move, and I now fully expect to be getting Pradaxa junk mail for years to come.
- Book a later flight for the last day to maximize the experience: The big sessions usually end around 5 pm. You can bring your bags and leave for the airport from the convention center.
Overall, this was an enlightening experience and with what I have learned, I hope I can get even more out of it next year…
Impressions From a First-Time Attendee
Eiman Jahangir
I am writing my reflections of the week on Friday, three days since I left the conference, and by now the week is already a blur. As a first-time AHA attendee (but frequent ACC attendee) I found the experience quite different. First, the magnitude of people seemed to be far fewer then I would have expected. Unlike prior conferences where just walking could be difficult due to the large numbers of attendees, this time certain areas, such as the exhibition hall and posters, seemed deserted. It may be because the device and pharmaceutical companies do not provide much “swag” anymore, thereby limiting the desire for attendees to listen to their promotion.
The next thing that I learned from attending AHA is to arrange meetings pre-conference. I made the mistake of thinking that I could just walk up to old attendings and colleagues after their talks and “catch up.” This was a dire mistake. I now know that everyone is busy (including me) during the week and meetings have already been arranged. Therefore, if you want to meet with someone, even if it is for a quick chat, I recommend emailing them and arranging a lunch, coffee, or just 15 minutes. I actually met individuals who did not attend a single scientific session, using the conference solely for socializing. It is also a good idea to have business cards on hand to pass on to those you may want to keep in touch with.
Finally, while the lectures are interesting, and you will come away with some new and exciting knowledge, most of this information can be obtained via the internet at a later time. Therefore, if you cannot see everything you would like to, don’t fret, because it will be available on line.
Now the question remains: Will I attend AHA again? I agree with John that, as we sub-specialize, we are more likely to attend our sub-specialty conferences. In my case this is TCT or SCAI. My only concern with attending the sub-specialty conferences is that I will then miss the opportunity to interact with my non-interventional colleagues. I guess I will just have to wait and see.
Summary Thoughts From AHA
John Ryan
The AHA meeting this year was an enjoyable, although at times overly busy, event. During this third year, I am doing research and clinical work in pulmonary hypertension. Therefore, inspired by Dr. Thomas Ryan’s advice, I decided to spend 60% of my time at pulmonary hypertension sessions. This actually was a feasible task as there were very few conflicting sessions. And pulmonary hypertension is so diverse (I am not joking, I have really gotten into it), that I was kept busy attending a variety of talks — there were right-ventricular sessions, pulmonary-artery updates and basic-science seminars on mitochondrial dysfunction in pulmonary artery smooth muscle cells. From this perspective, I left the sessions with a greater grasp of this field and the motivation to become a part of it.
To my regret, I found it harder than in previous years to make it to the late-breaking clinical trials. But this is a frequent observation of fellows and faculty alike: There is so much going on concurrently at the AHA that one can spend their time in almost a conference-center limbo, wandering from room to room and circling back to the exhibit hall. This year the late-breaking clinical trials were the best that I have seen since my first AHA. Part of the reason I enjoy these sessions is not only for the science but especially for the insight one obtains from the more senior investigators, either those presenting their work or serving as discussants. Seeing these senior cardiologists on the podium is an inspiring experience. Their dedication to the field and their clear interest in science serves as a reminder as to what we all hope to achieve by dedicating our lives to advancements in heart disease.
The AHA is always a place for reunions. For the first two years I met up with a lot of people from my residency. However, this being my third year, I noticed two differences: First, a lot of my friends have now decided which specialty they are going into and have opted to attend TCT or ASE as opposed to AHA. This was disappointing although understandable, and perhaps if there were an independent, stand-alone meeting in pulmonary hypertension, I would have opted for that, too. The second difference was a more positive change: Because my friends and I are getting more experienced, many more of them had presentations this year. As Dr. James de Lemos has previously pointed out, going to see your friends present is a remarkable experience. It is one thing talking to your former co-intern about their work over the phone or in the Peabody, but being in the crowd while they take the podium and watching their fear and confidence as they advance their slides is a heart-warming experience. Even if they do not see you in the crowd (and often times they are so stressed out that they do not), being there and watching them present the work that they have put so much effort into is something that never fails to satisfy.
When it comes to cardiology fellowship, while Braunwald’s may be required reading, going to see your friends present at AHA is required watching. And there is nothing that cements a friendship more than being able to say, “I was there.” Remarkably, it is also one of those feel-good bonds that reliably gets reciprocated whenever you present. And seeing familiar faces in the crowd (or at the very least knowing they are there) makes all the difference.
Observations From my AHA Experience
Amit Shah
As opposed to my first two AHA experiences, this one felt a little different. Perhaps it was the fact that I was going as a clinical fellow, which presented an entirely new set of challenges from when I attended as a research fellow last year. Perhaps it was the noticeably reduced attendance, and the refreshing lack of overcrowding? Or perhaps the nerve-racking oral presentations and last-minute preparations, chasing, and sometimes buying WiFi at every corner I turned to make the final tweaks on my talk?
Regardless, I’ve come to appreciate many things that were the same, such as the “aha!” (no pun intended) moments when learning about a study that shed some light on a clinical challenge or sparked a new research idea. Or the excitement when meeting someone with similar interests, and being on the cusp of a possibly new partnership in research. Like last year, I have also come to value my opportunity to blog with CardioExchange and engage in stimulating discussions with the other research-oriented fellows and online members across the country.
A few highlights from the sessions:
- I was surprised and refreshed to see late-breaking trials with a focus on prevention and cost-savings, such as Post-MI FREEE, as opposed to studies on new, expensive treatments that may offer only marginal benefits at great expense. With the trend of healthcare consuming larger amounts of GDP, it’s reassuring to see more work in this area. I hope it continues.
- I was only able to spend a few hours in poster-ville, but I was really happy I did so. Should have probably spent more, and in a more focused, organized way. For example, I was inspired by Chrysohoou’s poster on Mediterranean diet and systolic/diastolic function to look further into omega 3 fatty acids and diastolic CHF. This was just one of the many posters that I quickly bookmarked as I walked around.
Like Revathi, I also had some “maybe next year” moments…
- I agree about the dinners; they present a great opportunity to learn, network, and eat for free (some of them). I seemed to only learn about them too late, but regardless, had a great time with my other plans, so not all was lost.
- The expo hall indeed has all kinds of traps. Is anything in life truly free? Amongst other things, I was guilty of sneaking away a few packs of the walnuts for the road…but then again, they were preaching to the choir. I’ve been quite a walnut fan for some time!
Here are some tips I’d also like to recommend to a first-time AHA-goer…
- Bring business cards, even if you’re just a fellow – you never know who you might meet and want to keep in touch with.
- Use the excellent itinerary planner to look up not only your favorite research, but also to support those from your institution. For me, I just searched “Emory.” Even though you have plenty of time to connect back at home, it’s a little different when you’re all out of town together.
- Don’t sweat it if you miss a session; at the least, the abstracts are online, and if it’s anything like the years past, you will have free online access to recorded MP3’s of the talks you may have missed. You can otherwise get quite frustrated because of two great talks going on simultaneously.
Overall, it was a fun and hectic AHA, but also enlightening. Cheers to doing it all over again next year!
Other posts in this series:
- Evacetrapib – The New Wonder Drug? Drugs that increase HDL have failed to prove utility above statins alone. The pressure is now on evacetrapib to hit the game winning home run.
- Was AIM HIGH a Hit or a Miss? One of the best parts of AHA was the opportunity to hear experts on the panels dissect and interpret the data from a controversial trial.
- AHA Lessons on Emotions and Heart Disease: Depressing Data but Hopeful Trends: The many AHA sessions devoted to depression and heart disease gave renewed focus and drive to this researcher into the psychosocial factors of cardiovascular disease.
- POWER to the People: Two key lessons derived from this weight-loss study.
- An Event, Not a Conference: AHA requires both mental energy — science to be learned, posters to be read, and a program book the size of an encyclopedia to maneuver through — and physical energy — to hike to the various sessions spread all over this large conference center.
- MI FREE: A Free Lunch for Patients and Insurers Alike? Removing copays increased adherence, decreased events, and saved the sponsoring insurance company a tidy sum. So are the issues with insurance-sponsored studies different from those with pharmaceutical-sponsored ones?
- Go Red: Highlights from the Women and Heart Disease Session: Fascinating data on clinical and psychosocial aspects of heart disease in women.
- My First Oral Presentation: Life on the Other Side of the Podium: Not having to drag around a poster container was refreshing, but instead, this oral presenter was dragging around his dread.
- Finding Wisdom in Unfamiliar Ways in a Familiar Place: The Scientific Sessions are not the only way to learn at AHA.
- What’s Up, Interventionally? The latest in coronary intervention, including angiography for erectile dysfunction.
- Global CV Health Concerns: Macro and Micro: Now I know how to approach a potential mentor. But will it really take at least 10 years to train in research?
- Stenosis vs. Stroke: Is Treatment Worth the Risk? As a future interventional cardiologist and the grandson of someone who has suffered a debilitating stroke, a discussion of the PARTNER B trial results and TAVI really hit home for Jahangir.
- “The Center Where It All Happens”: This is the first AHA meeting for this participant who is deep in the trenches of her first year of fellowship.
- What Will Keep Me Coming Back to AHA? AHA attendance is on the decline, however, Ryan keeps coming back because of special seminars that delve into the heart of what he’s researching.
- Epcot for Foodie Cardiologists: Epcot’s survey of food from around the world sure beats this fellow’s memories of astronaut ice cream at Disney theme parks.
- An Unexpected Preconference Overload: Anyone else surprised by the volume of ad-driven snail mail and email – most of it junk – we all got in the run up to the conference?
- Part of the System: From AHA novice to conference veteran.
- AHA.11: How Does One Choose What to Do? How I’ll make choices among the dizzying array of options for how to spend time at the AHA conference.
- AHA.11: An Orlando Eating Tour: A guide to restaurants while you’re in Orlando.
November 18th, 2011
AHA.11 Roundup
CardioExchange Editors, Staff
Whether you were in Orlando for AHA.11 or not, you’ll want to check out our coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting.
VIEWS AND ANALYSIS
- ROUNDTABLE: After SATURN, What Role for Rosuvastatin? A CardioExchange Panel: Steven Nissen, JoAnne Foody, and Roger Blumenthal answer this question: Reading the results of SATURN in light of the impending arrival of generic atorvastatin, what is the appropriate role of rosuvastatin at this point?
- ROUNDTABLE: PALLAS Intrigue: What Role Remains for Dronedarone? John Mandrola, Eric Prystowsky, and Sanjay Kaul weigh in on PALLAS and the present and future of Multaq.
- At AHA, the Title Says It All: Susan Cheng lists some of the creative abstract and session titles that have caught her eye — and interest — thus far at AHA.11.
- Not Just Pomp and Circumstance: According to Susan Cheng, humanity and substance — not just ceremony — were to be found at the AHA Opening Session.
- AHA’s Best-Kept Secrets: Susan Cheng looks beyond late-breakers and plenary sessions to clue you in on the hidden gems at the AHA conference — events you shouldn’t miss, such as the Laennec session.
- ISAR-REACT 4: Bivalirudin Works Great, Less Bleeding: Rick Lange offers perspective on the randomized comparison of abciximab plus heparin versus bivalirudin in NSTEMI patients.
- Transapical TAVR on the Ropes: Is It Down for the Count? Citing lackluster data on transapical TAVR from the PARTNER substudy and negative results from STACCATO, Rick Lange and David Hillis ask, “What is the problem? Is it the procedure, the equipment, or the training? Should we stop the fight and throw transapical TAVR out of the ring?”
NEWS
THE FELLOWS’ PERSPECTIVE
Four of our fellows — Revathi Balakrishnan, Eiman Jahangir, John Ryan, and Amit Shah — shared their learning from and experiences of AHA.11:
- Evacetrapib – The New Wonder Drug? Drugs that increase HDL have failed to prove utility above statins alone. The pressure is now on evacetrapib to hit the game winning home run.
- Was AIM HIGH a Hit or a Miss? One of the best parts of AHA was the opportunity to hear experts on the panels dissect and interpret the data from a controversial trial.
- AHA Lessons on Emotions and Heart Disease: Depressing Data but Hopeful Trends: The many AHA sessions devoted to depression and heart disease gave renewed focus and drive to this researcher into the psychosocial factors of cardiovascular disease.
- POWER to the People: Two key lessons derived from this weight-loss study.
- An Event, Not a Conference: AHA requires both mental energy — science to be learned, posters to be read, and a program book the size of an encyclopedia to maneuver through — and physical energy — to hike to the various sessions spread all over this large conference center.
- MI FREE: A Free Lunch for Patients and Insurers Alike? Removing copays increased adherence, decreased events, and saved the sponsoring insurance company a tidy sum. So are the issues with insurance-sponsored studies different from those with pharmaceutical-sponsored ones?
- Go Red: Highlights from the Women and Heart Disease Session: Fascinating data on clinical and psychosocial aspects of heart disease in women.
- My First Oral Presentation: Life on the Other Side of the Podium: Not having to drag around a poster container was refreshing, but instead, this oral presenter was dragging around his dread.
- Finding Wisdom in Unfamiliar Ways in a Familiar Place: The Scientific Sessions are not the only way to learn at AHA.
- What’s Up, Interventionally? The latest in coronary intervention, including angiography for erectile dysfunction.
- Global CV Health Concerns: Macro and Micro: Now I know how to approach a potential mentor. But will it really take at least 10 years to train in research?
- Stenosis vs. Stroke: Is Treatment Worth the Risk? As a future interventional cardiologist and the grandson of someone who has suffered a debilitating stroke, a discussion of the PARTNER B trial results and TAVI really hit home for Jahangir.
- “The Center Where It All Happens”: This is the first AHA meeting for this participant who is deep in the trenches of her first year of fellowship.
- What Will Keep Me Coming Back to AHA? AHA attendance is on the decline, however, Ryan keeps coming back because of special seminars that delve into the heart of what he’s researching.
- Epcot for Foodie Cardiologists: Epcot’s survey of food from around the world sure beats this fellow’s memories of astronaut ice cream at Disney theme parks.
- An Unexpected Preconference Overload: Anyone else surprised by the volume of ad-driven snail mail and email – most of it junk – we all got in the run up to the conference?
- Part of the System: From AHA novice to conference veteran.
- AHA.11: How Does One Choose What to Do? How I’ll make choices among the dizzying array of options for how to spend time at the AHA conference.
- AHA.11: An Orlando Eating Tour: A guide to restaurants while you’re in Orlando.
PREVIEWS
- The AHA in Orlando: A Preview: AHA Scientific Sessions Program Chair Elliott Antman provides CardioExchange with a preview of the many expected highlights of the meeting.
- What’s This Fellow Looking Forward to at AHA? John Ryan discusses the studies he’s most looking forward to checking out at AHA this year.
- How to Prep for AHA: An Expert’s Advice for Fellows: Dr. Thomas Ryan explains how fellows can get the most from the AHA Scientific Sessions, both as attendees and as presenters.
November 16th, 2011
Evacetrapib – The New Wonder Drug?
Amit Shah, MD, MSCR
Several Cardiology Fellows who are attending AHA.11 this week are blogging together on CardioExchange. The Fellows include Revathi Balakrishnan, Eiman Jahangir, John Ryan (moderator), and Amit Shah. Read the previous post here. Check back often to learn about the biggest buzz in Orlando.
Stephen Nicholls happily presented impressive safety and efficacy data on the new CETP inhibitor—evacetrapib—at AHA while the paper was simultaneously released by JAMA.
HDL remains a mystery. Drugs that increase HDL have failed to prove utility above statins alone, as exemplified by the AIM-HIGH results. Torceptrapib, another CETP inhibitor, seemed like a dream drug till it was found to increase mortality. The pressure is now on evacetrapib to hit the game winning home run.
The investigators set up a complicated trial to test tolerability and efficacy of the drug at various doses (ranging from 30 mg/day to 500 mg/d) and in combination with various statins (atorvastatin, rosuvastatin, and simvastatin). Overall, 1154 dyslipidemic patients were screened, and 398 were randomized into ten different groups involving various combinations of statin therapy, evacetrapib doses, and placebo.
The bottom line in terms of efficacy was that evacetrapib showed a solid dose-response effect on both increasing HDL and decreasing LDL at 12 weeks, regardless of whether it was paired with a statin. At the maximum dose (500 mg/day) in the evacetrapib monotherapy group, LDL levels dropped a mean of 51 mg/dL and HDL levels increased a mean 66 mg/dL. Nonetheless, no significant differences in C reactive protein levels was found in any of the groups.
No life-threatening reactions were noted, and no CVD events were reported. Most importantly, no increases in blood pressure or cortisol-related effects—as were reported with torceptrapib—were observed.
Safety is very difficult to sell in such a small trial, but is at least a small step forward. I am looking forward to the next study evaluating outcomes. Given the bad karma of previous CETP contenders, it will be impressive if this drug can live up to the hype. It will also test an important aspect of the lipid hypothesis. Until the results come out, we will wait in suspense…
November 16th, 2011
Was AIM HIGH a Hit or a Miss?
Reva Balakrishnan, MD, MPH
Several Cardiology Fellows who are attending AHA.11 this week are blogging together on CardioExchange. The Fellows include Revathi Balakrishnan, Eiman Jahangir, John Ryan (moderator), and Amit Shah. Read the previous post here. Check back often to learn about the biggest buzz in Orlando.
In the weeks leading up to the AHA, there was much anticipation about the presentation of AIM HIGH amongst my co-fellows and attendings. Prior to starting fellowship, I did an additional year of training in preventive medicine, so the evidence for (or against) HDL therapy is of particular interest to me. The details of the study were described earlier on CardioExchange , but briefly, patients with cardiovascular disease, cerebrovascular disease or PAD with low HDL and elevated triglycerides were randomized to receive simvastatin combined with either niacin or placebo and were followed for differences in rates of cardiovascular events (CHD death, nonfatal MI, ischemic stroke, ACS, or revascularization). The trial was stopped early back in May, after 3 years of follow up, for “lack of efficacy” and concern for ischemic stroke imbalance (although overall rates were low). In addition, there was no significant difference for secondary endpoints, for cardiovascular death alone, and no differences between prespecified subgroups (by age, gender, diabetes, metabolic syndrome, history of MI, or statin at entry).
Sitting in the audience during the presentation, one could hear hushed rumblings throughout the crowd; the discussant, Dr. Philip Barter from The Heart Research Institute in Australia delivered probably the most dramatic commentary of the late breaking updates: “This study seriously disturbs me…because it was designed in such a way that it was not possible to get a positive result…” See the CardioExchange summary of the interaction.
He astutely pointed out faults in the inherent design of the trial:
- The study was powered to see a 25% reduction in cardiovascular events – an ambitious goal for follow up over 2.5 to 7 years
- Based on prior studies and the lipid goals attained in the study, the predicted CV event rate should actually be 12.5%, i.e., half of what the study was powered to detect
- The placebo group was placed on low dose niacin and attained HDL elevation; there was only a 4 mg/dl difference in HDL between placebo and treatment group, and only a 5 mg/dL difference in LDL levels.
Dr. Barter pointed out that given these issues it is difficult to draw conclusions from the findings in this trial that are generalizable to clinical practice, as the hypothesis that they sought out to test was not actually successfully tested. The panel concluded that the question of the benefits of HDL therapy with niacin has not been adequately answered by this trial.
When discussing HDL management of my clinic patients with attendings, I often hear diverse approaches and different opinions. One of the best parts of this conference has been the opportunity to hear experts on the panels dissect and interpret the data.
How have you been approaching patients with low HDL levels? How would you interpret this trial, and will it change your practice?
November 16th, 2011
ELEVATE-TIMI 56: One New Piece of the Clopidogrel Puzzle
Larry Husten, PHD
Jessica Mega
Tripling the maintenance dose of clopidogrel in most but not all patients with a common genetic variation will lower platelet reactivity to levels achieved in patients without the variation, according to results of the ELEVATE -TIMI 56 trial. The finding helps solve one piece of the clopidogrel puzzle, but does not provide a path to a major change in clinical practice. Results of the trial were presented by Jessica Mega at the AHA and published simultaneously in JAMA.
The TIMI investigators randomized 333 patients already taking clopidogrel. After genetic screening, 86 carriers of the CYP2C19*2 loss-of-function allele received clopidogrel doses of 75, 150, 225, or 300 mg daily; 247 patients without the allele received 75 or 150 mg daily. After 14 days, platelet function testing was performed.
The results show that tripling the maintenance dose to 225 mg daily achieved normal levels of platelet reactivity for the 80 heterozygotes with one loss-of-function allele. For the 6 homozygotes with two copies of the allele, however, the highest dose of 300 mg was insufficient to achieve satisfactory platelet inhibition.
At an AHA news conference, Mega said that the study offered some assistance to physicians if they are aware of a patient’s genotype: Carriers of one allele should be treated with higher-dose clopidogrel, while carriers of two alleles may be better served by prasugrel or ticagrelor. Mega acknowledged, however, that the trial offered no practical advice about when or how to perform genetic testing, a topic that is the subject of considerable uncertainty and controversy.
NEJM — Recent Cardiology Articles- Seeing the Left Main Coronary Artery Clearly — Is IVUS Always Necessary? June 11, 2026Treatment of the left main coronary artery with percutaneous coronary intervention (PCI) in the absence of previous surgical revascularization, also referred to as an unprotected left main coronary artery PCI, is one of the riskier tasks that interventional cardiologists are asked to perform. Stent implantation in the left main coronary...
- IVUS — A Zigzag Path to Success June 11, 2026The use of intravascular ultrasound (IVUS) imaging for assessment of the coronary arteries has an almost 40-year history. In an editorial comment on an early ex vivo assessment of the accuracy of IVUS in evaluating human coronary arteries, Yock and Linker1 posed three questions that remain relevant today:...
- Prescription without Precision — Dangers of Dosing on the Basis of Race as Biology June 11, 2026Despite recognition that racial and ethnic categories are poor proxies for genetic diversity, race is still used to guide pharmaceutical use, posing risks of ineffectively low or dangerously high dosing.
- Case 16-2026: A 14-Year-Old Girl with Hypertension June 11, 2026A 14-year-old girl was admitted to the hospital because of hypertension and headache. She had hypokalemia, an elevated blood level of C-reactive protein, and an elevated erythrocyte sedimentation rate. A diagnosis was made.
- Antidotes for Anticoagulation Reversal June 11, 2026The authors review current strategies for anticoagulation reversal in major bleeding events or urgent surgery as well as specific antidotes, limits of available evidence, thrombotic risks, unmet therapeutic needs, and ongoing research.
- Seeing the Left Main Coronary Artery Clearly — Is IVUS Always Necessary? June 11, 2026