RAY SUAREZ: For years, statins have been given to millions of patients with high cholesterol to reduce risk of heart attack and stroke. Now, a study in the New England Journal of Medicine finds one of those drugs, Crestor, may even provide significant benefits for those with low cholesterol.
It was funded, the study, by the drug’s maker, AstraZeneca, but because of its potential impact, it’s the subject of much attention at the American Heart Association meeting in New Orleans.
To explain the findings and put them in perspective, we turn to two cardiologists who are there: Harlan Krumholz, professor of medicine at Yale University; and Mark Hlatky, a professor of medicine and cardiology at Stanford University School of Medicine, who wrote an editorial about the impact of the study.
Dr. Krumholz, let’s start with you. What was this study designed to find out? What question were you trying to answer?
DR. HARLAN KRUMHOLZ, Yale University: Thanks, Ray. This is a study that sought to determine whether or not we could treat a group of people without heart disease, an apparently healthy group of people, whose cholesterol level was below what the normal — what the guidelines say would merit statins, that is a group that have no current indication for statin. Their cholesterol levels were low.
In fact, when you look in the trial, for those of your viewers familiar with these, the bad cholesterol level was about 108, so a level that we would consider within the normal range.
And the question was, for these individuals, who had, in addition, another laboratory test that suggested that there was an elevated level of inflammation in their system, something that we think is now associated with hardening of the arteries, atherosclerosis, and puts them at a little bit of an elevated risk, could these individuals with normal cholesterol, a slightly or elevated level of this marker of inflammation in their system, would they benefit from treatment with statins?
So this is a new group, a group that wouldn’t normally be treated with statins. Would they benefit by treatment with statins?
Marker indicates risk
RAY SUAREZ: That marker you discussed, that's CRP, C-reactive protein. What does its presence in the blood of someone you give a blood test to tell you?
DR. HARLAN KRUMHOLZ: Well, this is a test, C-reactive protein, it's a substance that appears in the bloodstream in response to inflammation. So inflammation is a process in the body in response to injury or infection. And it's been around since the 1930s.
But over about the last 20 years, we've recognized that differences in low levels of this marker, this protein, can indicate risk for cardiovascular disease.
And this study in some ways is a culmination of increasing attention towards this test in trying to see whether this test can identify a group that might benefit from certain interventions, in this case for statins.
So this test, C-reactive protein test, is really looking for a substance in the body that's a marker of an inflammatory process, something that we're now appreciating can be associated with hardening of the arteries, or artherosclerosis.
Dramatic results for drug
RAY SUAREZ: And the results, if you could describe them very generally and very briefly?
DR. HARLAN KRUMHOLZ: Yes, well, the results were pretty remarkable. What we found in this group was about a 44 percent reduction in the risk of cardiovascular events, things like heart attacks, including things like stroke or hospitalization for unstable angina, unstable condition that can lead to a heart attack, or death from cardiovascular causes.
Now, the thing that needs to be balanced here is this was a generally healthy population, so the rate of events was relatively low, but this drug, the addition of statins, lowered it even more.
So we went from about 14 events for every 1,000 patients treated for a year down to about 8, but about -- as I said, a 44 percent reduction, and very highly significant results, a very good result for statins.
RAY SUAREZ: Dr. Hlatky, a lot of your colleagues down in New Orleans who've been commenting on this study called it things like paradigm shifting, a milestone, but in your editorial you took a more cautious approach. Tell us why.
DR. MARK HLATKY, Stanford School of Medicine: Well, I think the reason that we need to be cautious is that potentially we're increasing the number of patients who are treated with drugs, lifelong drugs. And I think we need to be cautious before we expand the numbers of patients so drastically.
Basically, as Dr. Krumholz has said, these people have what would be thought to be normal levels of cholesterol and normal levels of bad cholesterol. And I think it's potentially very interesting that we may be able to find in that group the numbers of some people who benefit from treatment enough to be treated.
But I think that one of the other sides of it is that it's important, any time you think about drug therapy, to personalize the decision, to make sure that the risks and benefits are balanced in the individual patients.
So you need to look in every individual and say, "Is their risk high enough to justify going on a drug potentially for the rest of your life, paying for that drug?" This drug, for instance, that was studied is about $100 a month.
And we know about certain side effects of taking drugs, but other ones we don't know. And if we're talking about lifelong therapy for healthy people, I think we need a cautious approach to do this.
I would like to see professional groups, public health groups seriously consider these recommendations or this new data to revise recommendations about who ought to be treated and who ought to be tested.
Caution for life-long use
RAY SUAREZ: Dr. Hlatky, the sample was very large. From every indication, it was pretty representative, as well, of different subgroups in the population. Isn't a 44 percent reduction significant enough to take a serious look at this as a prophylactic drug?
DR. MARK HLATKY: Absolutely. It's a significant reduction that merits us looking at it. But let me just put it in context, because I think that you could have two different patients, one of whom has a pretty high risk, who qualified for the JUPITER study, for instance, somebody who has a very high risk of having heart disease in the next five years, and for that patient, if their risk is cut by 44 percent, they get a fair benefit from this.
And then they face the same risks, though, as somebody who's very, very low risk, who maybe only has a 1 percent chance of having any heart problems over the next few years.
There's a lot of differences between individuals and risk. We've heard a lot about personalized medicine, and I think that's an important thing. What that means is tailoring therapy to the individual's risk level and also taking into account their attitudes and concerns about risks and benefits.
Statins provide options
RAY SUAREZ: Dr. Krumholz, what about that suggestion? You heard Dr. Hlatky say that, until we understand the risk group better, moving to using statins as a preventive medicine might be too much, too soon.
DR. HARLAN KRUMHOLZ: Well, I think there are a couple of things here. Look, we like to deliberate on new studies. And this is only day two. It was just released yesterday.
But, first of all, this study shows us -- I think without much question -- that this is a group that we could have only speculated about a benefit before that is providing us fairly strong evidence.
In fact, this study was terminated early, ended early because the effect was so large that they saw no need to continue to the end because of the virtual certainty that this was going to show the result that they ultimately got, which was that it was beneficial.
But I do agree very much with Dr. Hlatky, in the sense that it's very important for us to engage in conversations with our patients. There needs to be an understanding that here now is an option, a strategy that's been shown to be effective.
Whether or not it is right for an individual depends on that person's values and preferences and goals, how they feel about taking medications, what their situation is with regard to wanting to lower their risk, and how does this strategy compare with other strategies?
It's a complex, complex issue. But I don't think there's any question that we now have identified a group for whom statins can lower risk, and it's a group we didn't know about before.
And it again sort of reinforces the pre-eminence of statins as the drug of our generation, a drug that's very safe. That doesn't mean that there aren't occasional side effects, but very safe and has time and time again shown that it can reduce risk.
Now our job is to work with our patients to make sure that there's proper selection of the patients and that we work together in making a decision about whether it's right for you, whether it's right for an individual patient, given their situation.
But this has the possibility of markedly expanding the number of people for whom now we know statins could be effective in reducing risk.
RAY SUAREZ: Very quickly, before we go, Dr. Hlatky, what do you need to know before you are ready to look upon this as a possible prophylactic medicine?
DR. MARK HLATKY: For patients, I think they need to know their individual risk levels. For society, I think we need to say there are also other proven things to reduce heart disease that we shouldn't lose sight of, like following sensible diets, keeping our weight down, exercising, not smoking.
All of these things are vitally important. And I think that we shouldn't be taking a pill before we start doing some of those things first.
RAY SUAREZ: Doctors, thank you both very much.