Commentary By: Steven Sedlis, MD Associate Professor of Medicine, Chief, Division of Cardiology Manhattan Veterans Administration Medical Center
This year’s AHA meeting was held in November in Orlando Florida. The cardiology fellows were not overly distracted by the attractions at Disneyworld – the social event of the week, cocktails in the lobby of the Rosen Centre Hotel with Glenn Fishman, Barry Rosenzweig, Jennifer Mieres and me was not much of a distraction either – so the fellows were able to concentrate on the business at hand, basic and clinical science. The fellows did stay at the Hard Rock Hotel at the Universal Orlando Resort, but I didn’t hear much about what went on there. I guess what happens at Hard Rock stays at Hard Rock.
This report features the presentations given by the fellows at cardiology journal club after their return from the meeting. We began by discussing the late breaking clinical trials.
Adam Skolnick commented on the Occluded Artery Trial (OAT) quality of life substudy presented by Dan Mark, director of outcomes research at Duke Clinical Research Institute. OAT showed that there was no improvement in survival with a routine strategy of coronary stenting in patients with an occluded infarct-related artery 3-28 days post infarction. The quality of life study done in OAT patients from the United States showed that coronary stenting was associated with a clinically significant benefit in physical functioning at four months, but this benefit was not sustained at one year or beyond. There were no significant effects on psychological well being. Of the secondary quality of life outcomes, stenting was associated with a modestly lower level of angina at four months and one year but these benefits also diminished over time. The cost effectiveness ratio for stenting was significantly greater than $100,000 per quality adjusted life year, not an economically attractive strategy.
There were numerous substudy presentations at AHA from the COURAGE study. These presentations for the most part supported the main findings of COURAGE that a routine strategy of coronary stenting for patients with stable angina does not improve infarct-free survival. I was particularly impressed with the findings of the severe angina substudy presented by David Maron from Vanderbilt. This substudy focused on the 12% of COURAGE patients with high risk angina defined as onset of class 3 angina within 2 months or recently stabilized class 4 angina and showed that these patients did as well with an initial strategy of optimal medical therapy as with stenting. The most widely discussed and controversial COURAGE presentation was the nuclear stress substudy presented as a late breaking trial by Leslee Shaw from Emory. This study showed that stenting was more effective than medical therapy for reducing stress induced myocardial ischemia as measured in the core nuclear lab and also showed that extent of residual ischemia on stress testing predicted death and myocardial infarction. It is not surprising that stenting is effective for relieving ischemia – that is what stenting is supposed to do. That residual stress induced ischemia predicts survival is surprising and contradicts the main COURAGE findings. If stenting is better than optimal medical therapy for suppression of stress induced ischemia and ischemia predicts survival why didn’t COURAGE show a beneficial effect of stenting on outcomes? One possible explanation for this discordant finding is the small and selected population in the substudy (only 313 patients out of the total 2,287 patients enrolled in COURAGE). Another criticism of this substudy and of nuclear stress in general that was brought up during the discussion at AHA is the discrepancy between the quantitative scores provided by the core nuclear lab at Cedar Sinai headed by Dan Berman and the interpretations (often qualitative) done by local labs. The Cedar Sinai lab is widely recognized as one of the finest in the world; if their readings cannot be reproduced by less sophisticated nuclear labs in the community it brings into question the generalizability of the substudy findings and the reliability of nuclear stress testing as commonly practiced. Better nuclear cardiology training and wider use of rigorous and well validated quantitative scoring systems such as those used by Jennifer Mieres here at NYU will be part of the answer for sure.
There were other surprising and disappointing results reported at the late breaking trials. The Corona study, for example, failed to demonstrate that statin therapy was beneficial for elderly patients with ischemic heart failure. The largest study to date of T wave alternans testing, the MASTER I study, failed to show that this test could predict ventricular arrhythmias in high risk patients, and POISE questioned the strategy of routine beta blockers for non cardiac surgery. “So” said Jeff Lorin when told of all these negative results “no more stents, no more statins, no more stress tests and no more beta blockers.”
The fellows were not quite as nihilistic as Jeff. They chose the following studies to highlight:
Binita Shah commented on TIMI 38 –the Triton study which compared the novel ADP receptor blocker prasugrel to clopidogrel for acute coronary syndrome. Prasugrel provides more rapid and more predictable platelet inhibition than clopidogrel and in this study treatment with prasugrel resulted in fewer ischemic complications than treatment with clopidogrel, but at the cost of more bleeding. Eugene Braunwald (NYU class of 1952) is very excited about prasugrel. To see what Binita Shah (NYU class of 2004) thinks, read her presentation.
Zev Frankel presented the results of the RethinQ trials. This was another negative trial which showed that cardiac resynchronization therapy for patients with narrow QRS was not effective even if there was evidence of dyssynchrony on echo. Read all about it in his presentation.
Will Shin, a true basic scientist, spoke to us about “In Vivo Visualization of Embryonic Stem Cell Survival, Proliferation, and Migration After Cardiac Delivery ” which was chosen as the best basic science presentation at AHA. Will reviewed the field of stem cell therapy for heart failure and pointed out important concerns including the potential for development of malignancy – Will calls it “cellular misbehavior”. The authors of the study reported by Will transfected stem cells with a genetic construct including a truncated thymidine kinase which could act as a suicide gene on treatment with gancyclovir protecting patients against any possible “misbehavior” by the stem cells. To get a glimpse of the cardiology of the future, look at this fascinating presentation.
Finally, getting back to the world of real-life medicine and to a topic of great interest to all of us, especially those involved in the medical management of patients undergoing non-cardiac surgery – the POISE study enrolled 8351 patients with coronary or vascular disease or history of heart failure randomized to 100 mg controlled-release (CR) metoprolol or placebo two to four hours before surgery and between zero and six hours after surgery. Twelve hours following the first post operative dose, patients were started on 200 mg CR metoprolol or placebo for 30 days. If at any time patients could not take doses orally, 15 mg of metoprolol or normal saline was given IV. POISE showed that metoprolol reduced the risk of myocardial infarction, but there was excess stroke and death in the treated group. Susie Hong gave us a great presentation on this important study. POISE is not yet in press, but as soon as it is published Susie promised that she would post her presentation on the blog. Stay tuned.