November 6th, 2012
What Tack to Take in Thinking about TACT?
Reva Balakrishnan, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
In my short experience at AHA.12, I have noticed several differences this year, most notably that several presentations at the early Late-Breaking Clinical Trials sessions left us with mostly negative results and more questions.
During the first session, one presentation with a positive result seemed to catch the fellows (and perhaps many others in the audience) off guard — TACT (Trial to Assess Chelation Therapy). When the introductory slide appeared, we all seemed to be thinking, “What is chelation? And why is this important?” Although some presentations at these conferences can seem beyond our knowledge base or secondary to our personal experiences within the specialty and training, it is rare that during a major session a therapy is presented that only few of us are even remotely familiar with. Except for reading about chelation therapy for lead poisoning in medical school, the most experience I have had with it was seeing an old enrollment binder sitting in the back of one of the fellows rooms and asking an attending about it (who quickly dismissed it with an “oh, nobody does that anymore, don’t worry about it” type of statement).
The surprising trial results raised more questions than answers, showing that chelation therapy was significant (HR 0.82, with an upper limit of 0.99) in reduction of the primary composite endpoint of all-cause mortality, MI, stroke, revascularization, and anginal hospitalization, with what appeared to be a stronger benefit in the subgroup of diabetics (39% reduction in events, p=0.002).
I searched the internet for some information on plausible mechanisms of action — and could find no strong evidence, instead seeing mostly theories.
Later that night, our fellowship program convened for a reception. One aspect that makes the conference valuable for fellows is the opportunity to discuss the presented results with a diverse group of people at different levels of training, plus researchers and clinicians, which allows us to more fully synthesize the data and explore different approaches to thinking about the information.
At the reception, I was able to discuss the trial with more senior faculty with extensive research backgrounds. One highlighted thought-provoking point was that our impression of a major finding is oftentimes shaped by the bias of the presenter. Although this trial had a significant result, the overall tone from the panel was negative, and the author at an AHA press conference even called for caution in interpretation. The attending at my evening reception believed that if similar results were presented on a new drug or stent, people would likely be more excited about it and the study might change their practice. Yet, given that biologic plausibility is not established and closer analysis of the data remains to be seen, it seems appropriate to approach these results with a critical eye.
As a fellow, have you had any exposure to the practice of chelation therapy for CAD, either first-hand or through the grapevine? More generally, how do you think about studies with surprising results?
November 6th, 2012
Using the Internet to Learn from Leaders in Cardiology
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Prior to coming to the AHA, I spent quite some time playing with the AHA iPhone app, making a list of the talks I would be interested in attending, and linking up speakers with some of their recent publications. This way, when I listened to the speaker, I would be an “intelligent” consumer of information.
This method of learning is quite new: previously text books, journals, and lecture halls were the major method by which information was distributed. At this year’s AHA, the Internet seems to be playing as much of a role (if not more) in the dissemination of information as the physical location of the meeting. Lectures can be watched online, and many of the attendees read about the trials being presented on cardiology news websites and blogs.
However, the contextualization of presented data and discussions by world experts in the field are, for me, the major draw of the AHA. My co-fellows and I have been trying to use social media to capture some of the wisdom provided by leaders in the field of cardiology and share it with our colleagues. We try to ask key faculty members a few questions about their area of expertise, and post it on our fellows’ blog for others to watch.
Major meetings like AHA have been particularly good for this purpose because they provide us with access (for a few days) to cardiologists from all over the world, with a wide variety of interests. Hopefully, in the future, the Internet will make access to the wisdom and advice of the cardiology “greats” accessible to everyone, not just those attending these meetings.
November 6th, 2012
Acknowledging our Mentors, Both Faculty and Peers
Megan Coylewright, MD MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Last night we came together to celebrate with one of Mayo Clinic’s beloved faculty members, Bernard Gersh, who received the James B. Herrick Award at this meeting. The occasion is a reminder of the amazing drive and passion of those who love to mentor. Dr. Gersh has provided encouragement, support, and guidance to many and, like the most effective mentors I know, is still visibly in love with his work. It is hard to know how best to say thank you to those who generously give of their time and energy.
At the meeting, I catch up with Karen Joynt and Susan Cheng, both from the Brigham — and both impressively prolific and yet new on staff. I am aware of the benefit of “peer mentoring” when those just a few years ahead of you, or in the same year, share new ideas, resources, feedback. I am left thinking that our thanks will be shown in our doing the same as we transition from fellows to faculty.
This meeting is invaluable for building these essential relationships that will last a career.
November 6th, 2012
Cardiology Circles and the AHA
Tariq Ahmad, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
When planning my trip to the AHA meeting, I had three major goals: to meet old friends, to make connections, and to learn about new science.
Since arriving here, I admit that I have spent the majority of my time on the “social” goals. Soon after arriving at LA on Sunday, I quickly made my way towards the convention center to attend the late breakers. En route, I ran into friends from residency and spent quite a bit of time catching up (time well spent, I must add). We spoke about our clinical and research interests and the differences between our training programs.
During the late breakers, I bumped into the first cardiology attending I ever had as an intern, and he asked me about my current research and future goals. As always, he gave me sage advice.
Soon after the presentations were over, I met my co-fellows and attended the Duke Reception for current and past trainees of the program. This turned out to be an excellent opportunity to socialize with faculty members in an entirely different way, as well as to meet previous trainees at other major institutions who were nostalgic about their time in fellowship and eager to talk to current fellows.
After the reception, our fellowship program director took us out to an excellent Spanish restaurant. Once again, we were able to mingle outside of the work setting. I learnt more about some my co-workers in one night than I have after having worked with them for more than 2 years.
The next day, I felt guilty about having traveled across the country only to spend the majority of my time with people from back home. I shared this thought with my colleagues, but to my surprise, they had very similar experiences. AHA is primarily about developing and forming new connections, they said. One particularly cynical cardiology fellow (who shall remain unnamed) said that he could always read about the results on a popular cardiology website, but there was no better venue for networking.
This might be an important sentiment, especially as people increasingly use the internet to learn. Certainly, for me, the social interactions during this meeting have had the highest “yield.”
Google “Circles” allows us to organize our friends according to level of importance. I think that meetings such as the AHA give us the opportunity both to enrich our own current “circles” and to add new ones.
However, the one aspect of this meeting I have found ironic is that so much time is spent at these meetings with people who are already in your inner circle and so little time getting to know new people. Please weigh in: Has this been your experience? Would our time be better spent making new connections?
November 6th, 2012
Late-Breaking Trials vs. Abstract Oral Sessions
Eiman Jahangir, MD
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Over the last 48 hours, I, like most others, have attended a mix of educational and abstract presentations and browsed both the poster and exhibition halls. One area I have not spent time in is the Late Breaking Trials. While it may seem that these would be the most exciting and the most sought-after sessions, for me, they make the least valuable use of my time. The beauty of the Late Breaking Trials is that as soon as the embargoes are lifted on the outcomes, the information is quickly disseminated over the Internet through various blogs, journal sites, and Twitter feeds. Therefore, even without attending, I am quickly able to learn what has been announced. While I may be missing the excitement and energy, I am not missing the data.
On the other hand, the abstract oral sessions are the most valuable to me. These not only provide new and interesting research in its beginning stages, they also provide data that is not as quickly or widely disseminated online. Additionally, it is in these smaller sessions that I am able to see my friends, such as former co-residents and co-fellows, present the work that in some cases has taken many years to complete. Therefore, attending these sessions is always more exciting to me as I am able to see my colleagues honored for the effort that they have placed in their research while training.
Which sessions do you find most valuable?
November 5th, 2012
Early Look: New Methods to Enhance Cholesterol Efflux
Larry Husten, PHD
Although clinical trials of HDL-boosting CETP inhibitors have so far failed to produce positive results, many other avenues of HDL-related research remain active. Conference attendees got a glimpse of the very early phases of two intriguing lines of research in this area on Monday.
Apoliporotein A-I is thought to be the key HDL component that removes cholesterol from cells. Almost a decade ago, a study demonstrating regression of atherosclerosis with apo A-I Milano caused tremendous excitement, but the recombinant product has not yet undergone further research or commercial development. A somewhat similar approach is now being developed by by CSL Limited with a novel formulation of human apo A-I, known as CSL112. At the AHA, Andreas Gille and colleagues reported giving CSL112 to healthy volunteers and observing dramatic increases in the ability of the HDL in their blood plasma to remove cholesterol from cells.
Gille reported that the increase in cholesterol efflux capacity was higher and occurred faster than any previous therapy, more than doubling within two hours, as opposed to a 2.9% increase after 4 weeks with niacin or 6.8% after 24 months with dalcetrapib. “CSL112 may offer a novel means to rapidly remove cholesterol from plaque following a heart attack,” said Gille. To date, two phase 1 studies have demonstrated a favorable safety profile, he reported. A phase 2 study of CSL112 in patients with an acute coronary syndrome is planned.
An even more unusual approach is being explored by Alan Fogelman and his team, who have genetically engineered a tomato to produce a small peptide, 6F, that mimics the action of apo A-I. They then fed the tomatoes to mice with high LDL levels. After consuming the tomatoes along with a high-fat and high-calorie diet, a number of signs suggested a beneficial effect, including significantly lower levels of inflammation, higher levels of the antioxidant paraoxonase, higher HDL levels, and less atherosclerotic plaque.
“To our knowledge this is the first example of a drug with these properties that has been produced in an edible plant and is biologically active when fed without any isolation or purification of the drug,” Fogelman said in an AHA press release.
For related CardioExchange content, go to our AHA 2012 Headquarters page.
November 5th, 2012
What’s the Value of the Expo?
Reva Balakrishnan, MD, MPH
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
Regulations have limited the amount of “freebies” that companies can give fellows, and our training starting in medical school has discouraged interaction with industry. Sometimes, though, wandering into the colorful room full of distractions from the main event can be unavoidable .
Therefore, friends and I entered the Expo room at AHA.12 with a discerning eye, gaining little educational value but walking away with some laughs instead. One of my cofellows tested her chest compression skills (and found out — way too fast!). Amusingly, some booths were not successful in their marketing strategy (see picture). Even at the fellow level, I’d hope you wouldn’t need a special stethoscope to hear S1 and S2!
So, similar to the previous year, I found little value in the Expo floor except for some laughs. Do you gain any value from the booths?
photo credit: Kelly Axsom
November 5th, 2012
Dalcetrapib: Another HDL-Raising CETP Inhibitor Bites the Dust
Larry Husten, PHD
Another HDL-raising CETP inhibitor has failed to demonstrate cardiovascular benefit in a large clinical trial. With the presentation of the dal-OUTCOMES trial at the American Heart Association in Los Angeles and simultaneous publication in the New England Journal of Medicine, dalcetrapib joins torceptrapib on the list of once-promising CETP inhibitors.
In dal-OUTCOMES, 15,871 patients with a recent acute coronary syndrome were randomized to dalcetrapib or placebo. At a prespecified interim analysis after a median follow-up of 31 months, the Data and Safety Monitoring Board recommended termination of the trial for futility. The primary endpoint — a composite of death from CHD, nonfatal MI, ischemic stroke, unstable angina, or cardiac arrest with resuscitation — occurred in 8.3% of dalcetrapib recipients and 8.0% of placebo recipients (HR, 1.04; 95% CI, 0.93-1.16; P=0.52).
As expected, dalcetrapib raised HDL (by about 30%) and had little effect on LDL. However, there was no correlation between baseline HDL level and clinical outcome. Furthermore, dalcetrapib treatment resulted in mean increases of 18% in CRP level and of 0.6 mm Hg in systolic blood pressure.
The chair of the trial, Gregory Schwartz, said that the small increases in blood pressure and CRP might explain the results. The discussant for the trial, Alan Tall, said that the decision to stop the trial prematurely was rational. In addition to the changes in blood pressure and CRP, he offered several additional possible reasons for the drug’s failure to improve outcomes:
- Moderate HDL elevation in patients who are already well treated may have little impact. It is possible that much larger elevations in HDL will be required to alter the course of disease.
- CETP inhibitors may produce a form of HDL that does not enhance reverse cholesterol transport.
- Dalcetrapib is only a partial CETP inhibitor. Phase 3 trials of more-potent CETP inhibitors, such as anacetrapib and evacetrapib, may still demonstrate benefit.
For related CardioExchange content, go to our AHA 2012 Headquarters page.
November 5th, 2012
Selections from Richard Lehman’s Literature Review: November 5th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
BMJ 3 Nov 2012 Vol 345
Fish Consumption, Omega-3 Fatty-Acids, and Cerebrovascular Disease: Yes, Jeeves was right: fish is good for the brain. I have told you this before: here is a systematic review of the protection afforded by fish consumption against the risk of cerebrovascular disease. It’s not just the oils: “the beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.” But actually I couldn’t give a hoot: “dietary science” is just a mess of confounders: I eat fish because I like fish.
HRT and Cardiovascular Events in Recently Post-Menopausal Women: This week sees the print version of the now-famous Danish randomized trial of hormone replacement therapy that contradicts the Women’s Health Initiative and shows a cardiovascular protective effect from the early use of HRT. I will leave it to others to discuss the timing hypothesis and so forth. What we need are some good decision aids for women. I nearly said “patients” – but why should taking HRT turn people into patients? Why should doctors in fact have anything to do with an informed woman’s decision about using HRT for postmenopausal symptoms?
Using a Meta-Analysis of Coronary CT Angiography Studies to Assess Diagnostic Tests with a 3×2 Table: All doctors need to become competent diagnosticians. Yet most that I have encountered find it difficult even to use a two-by-two table to assess diagnostic tests. This is not going to change. This important article, based on a meta-analysis of coronary CT angiography studies, urges the adoption of 3 by 2 tables, with an intermediate category of “non-evaluable”. I believe the authors are right: and I believe also that once we have made this move forward, we then have to find ways of making it intuitive and practical for jobbing clinicians.
November 5th, 2012
Reclassifying AHA on the West Coast
Amit Shah, MD, MSCR
Several Cardiology Fellows who are attending AHA.12 in LA this week are blogging together for CardioExchange. The Fellows include Tariq Ahmad, Reva Balakrishnan, Megan Coylewright, Eiman Jahangir, Amit Shah, and John Ryan (moderator). Read the previous post here. Find the next one here. For related CardioExchange content, go to our AHA 2012 Headquarters page.
After 3 years of East Coast AHAs, I was a little surprised to learn that the 2012 Scientific Sessions was being held in Los Angeles. Admittedly, it was a little tough this year, with things being busier at home than ever before. Nonetheless, I was curious and excited to see how things would be different.
After taking the airport shuttle to my hotel, I caught the convention shuttle just in the nick of time. The ride was appreciated! I was staying 10 miles away in Universal Studios. Public transportation would have taken 3 times as long, and repeated cabs would have broken the bank. On the way there, we witnessed an overturned car in the opposing direction. “I was just on that road 20 minutes ago!” my driver commented. Thankfully it was smooth sailing for us…. Who knows what tomorrow will yield, though, when we wade through rush hour….
I hit the ground running at the convention. Noticeably, it seemed quieter than previous years. Perhaps it was just that time of day, but I did not feel swarmed by masses of curious poster-carrying scientists as in previous years. One thing did not change, however; the Starbucks line was packed!
Eventually, I made my way to the epidemiology evening session on risk prediction. It was the perfect prelude for my presentation tomorrow, which is on the same topic. In a series of excellent talks, several relevant and interesting points were made that stuck in my mind:
- Statin use for primary prevention should be considered in light of the number needed to treat against the number needed to harm (myopathy, diabetes). For lower risk patients, the NNT is high and can approach the NNH, depending on the dose of the statin. Simvastatin 80 mg in South Asians may be a bad idea in terms of myopathy!
- Multiple risk factor equations exist, but the complicating matter is that they use a variety of endpoints; some include stroke, whereas others do not. The Framingham risk score itself sets a high bar. Only coronary artery calcium scoring consistently shows a significant benefit over other risk predictors such as carotid IMT.
- Calcium scoring may be motivational for lifestyle change to patients with positive calcium scores, but the jury is still out, since it motivates doctors as much as it does their patients. Whom does the credit go to?
- Lifestyle change is always challenging; just because a patient is motivated to eat healthy after a heart attack does not mean that she or he will stick with the new habit for long. This maintenance and execution is what makes lifestyle change so difficult. Advanced techniques/strategies may be required. Can we accomplish these in a 15-minute office visit? Another option: we can just increase the Lasix dose as our patients eat more salt!?
Looking forward to an action-packed day tomorrow….
