November 6th, 2012
What Tack to Take in Thinking about TACT?
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?