What is your current medical research focus?
I’ve been involved in clinical trials helping test new drugs for heart attack and patients with worsening chest pains, or “pre- heart attack”, over the last 10 to 12 years and that has continued to be my area of focus. Fortunately it has been a lot of fun because there have been a lot of new treatments for these patients available in the last decade.
What were the most significant findings of TACTICS-TIMI18 study?
In the TACTICS-TIMI18 trial we studied patients with worsening chest pain who had to come to the hospital or who had small heart attacks, much like Vice- President Cheney about a year and a half ago. When he first came to the hospital he had worsening chest pains and had developed a small heart attack. And so the question that this trial addressed was, what is the best way to treat people like him? Now this is a big question because there are1.4 million people a year who come to the hospital with this condition, which is 1 every 22 seconds. It is very common in people who have known things wrong with their arteries; this would be when things get worse. The question is: Should they get treated with medicines, or should they go off for cardiac procedures? We tested that by giving everyone in the trial the best possible medicines, and then some people were watched and later had a stress test. If they failed the stress test after a few days of medical treatment then they went on for cardiac catheterization where you look at the arteries and have any blockages fixed. The routine course assigned to another group was, if you came into the hospital with worsening chest pain, we’d say, “Gee, you’ve failed the medicines you were on previously, let’s go take a look at the arteries and fix them.” And what we found was that going directly to the cardiac procedures led to fewer second heart attacks, deaths and re-hospitalizations. So if you do come to the hospital, you should expect as patients to be sent--- and for doctors, to send your patients--- onto cardiac catheterization to try and move quickly to fix the problem then. These results have been out a year or so and hopefully guide the overall treatment. It is certainly talked about a lot amongst cardiologists as the best approach to treating this large group of patients. There have been advances even since this trial of a new anti- blood clotting medicine that has come along called clopidogrel (Plavix) that we would now simply add to everything we did in TACTICS-TIMI18. I guess that is the biggest finding from our trial.
Can you explain the difference between acute coronary syndrome and heart attack?
Acute coronary syndrome includes patients with heart attacks and those with worsening chest pains who have to come into the hospital. Heart attack actually means that there has been damage to the heart muscle, so when you do a blood test you’ll see dead heart muscle floating around in the blood. For other people who have the same symptoms but do not have the damage to the heart, they clearly have problems in the heart arteries that are threatening a heart attack, but fortunately it is caught early enough. The term acute coronary syndrome is a broader term that includes both of these groups of patients, and they are actually about equal in number. There are about 750, 000 heart attack patients per year who are admitted to the hospital and the same number with “unstable angina” or just the worsening chest pains without heart damage. We traditionally talked about the 1 million heart attacks a year, and that probably includes the number of people that die suddenly at home from a massive heart attack who cannot even get to the hospital for a diagnosis.
Many hospitals in the U.S. do not have access to cardiac catheterization labs. After the TACTIC-TIMI18 findings were published, have you seen any effect on hospitals in the community?
What we’ve seen is that about 20% of hospitals have cardiac catheterization procedures. However, lots of patients admitted to a hospital initially without cardiac catheterization labs are transferred to the tertiary care hospitals, so probably half of the patients that come for the procedure are from other hospitals. That proportion seems to be increasing, but I haven’t seen any hard numbers from national registries or things like that. Just anecdotally talking to people. The guidelines have just been updated 3 or 4 weeks ago incorporating the findings from the trial, to say that more patients need to go on to cardiac catheterization. Amazingly enough, it usually takes us docs about 1 to 4 years before we get all the way up to full implementation of any new finding, so it may be early still. We hear that there are changes, but I don’t have anything to point to saying that it has changed.
Do you see any similarities between the TACTIC-TIMI18 trial and the MADIT II trial on implantable cardiac defibrillators (ICDs)?
These 2 trials are similar in the way that they define optimal practice. The patients that were studied in the trial were different. The MADIT II group studied one of the more extreme ends of the spectrum of acute coronary syndrome—people with big heart attacks. But they found the same thing: that being aggressive with interventions—in this case electrical interventions—was better than medical therapy. There was also an editorial recently in JAMA that the “middle group” of the spectrum, ST elevation myocardial infarction, was better with interventions. So these 2 trials and the other recent trials on primary angioplasty all are pointing to the benefits of interventions in patients with heart attacks and acute coronary syndromes. In fact, my mantra is, “All roads lead to the cath lab!” So MADIT II is really a landmark trial. It broadens the scope of what we were thinking of in TACTICS-TIMI18, to start thinking about the electrical part of the heart in the standard acute coronary syndrome patient. It is an important component of things we have to think about. When we think about cholesterol and heart rate and blood pressure, we really need to add to our thinking the electrical system in terms of what we need to try to treat for long- term prevention.
In your opinion, what do you think is the biggest takeaway for patients from the MADIT II trial?
I think from this trial and the whole body of evidence, patients should look favorably on interventions. I think we already do in general, but now there is just more and more evidence that aggressive interventions, be it on the coronaries or on the electrical system, are really beneficial in preventing future events. So patients certainly should be asking questions like, “Shouldn’t I be getting a cath?” or “What is my ejection fraction?” Or if it’s a big heart attack, “Do I have to worry about a ‘pacemaker plus’ (as Cheney’s press office calls it)?” Certainly in this era there is more dialogue between patients and doctors, which is terrific. On the MADIT II, interestingly enough, the initial response from doctors has been, “Oh my goodness, we can’t afford this.” And the patients have to be their own advocates and say, “Wait a minute. If I’m eligible for this, please consider it. I don’t want to not get something just because it might be too expensive.” Whereas it may turn out to be cost- effective when they run the final analyses.
Do you feel that the study has changed your views about educating your patients about ejection fraction specifically?
Sure. I think we generally try and talk about that and even beyond ejection fraction, about the electrical system problem and risk of sudden death. Everyone seems to know about their cholesterol, but about dropping dead--- people don’t really talk about it. It’s obviously not really a pleasant thing to talk about, but in these high- risk patients it’s something that really should be. Already, I’ve changed my practice. You see a big heart attack and now you have to think about electrical issues and you have to sort out if this patient should be getting treatment.