Treatment Options for the Stage C Heart Failure Patient

ADOLPH M. HUTTER, JR., MD: Hello. I'm Dolph Hutter. Welcome to the American College of Cardiology Conversations with Experts. In this program, we will review treatment options for a stage C heart failure. Joining me to discuss this topic is Dr. Lynne Stevenson, Director of the Cardiomyopathy and Heart Failure Program at the Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School.

DR. LYNNE W. STEVENSON, MD: Happy to be here.

ADOLPH M. HUTTER, JR., MD: Dr. Marvin Konstam, Chief of Cardiology at the Tufts New England Medical Center and Professor of Medicine at Tufts University.

MARVIN A. KONSTAM, MD: Thanks, Dolph.

ADOLPH M. HUTTER, JR., MD: And Dr. Marc Semigran, Director of the Cardiac Transplant and Heart Failure Program at the Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School.

MARC J. SEMIGRAN, MD: Thanks, Dolph.

ADOLPH M. HUTTER, JR., MD: Well, thank you all for joining me here today. This is a very timely topic, and a lot to cover. We're talking about stage C heart failure. What is that, Lynne?

DR. LYNNE W. STEVENSON, MD: Stage C heart failure is the patient who has symptoms of heart failure. And once you've had symptoms of heart failure, you're always a stage C patient, even if therapy actually makes you better. So that's how it's different from the New York Heart Association Classes, in which you can go back and forth a lot.

ADOLPH M. HUTTER, JR., MD: So once you're stage C, you're always stage C?

DR. LYNNE W. STEVENSON, MD: Or you can get worse and go on to stage D, but you never go back.

ADOLPH M. HUTTER, JR., MD: Okay. Very good point. Now, we've got a lot to cover. Let's start with diuretics. Marv, We have the patient with symptomatic heart failure. What do we start with?

MARVIN A. KONSTAM, MD: Well, you know, a principal therapeutic goal, both for symptom relief and improving functional status, is to get the patient in some kind of a normal volume status. And clearly, heart failure is often manifest by volume retention, so diuretics remain a mainstay of our therapy, and depending on what the volume status is, we may need to be fairly aggressive with diuretics in the early stages of treatment.

ADOLPH M. HUTTER, JR., MD: Are you talking mostly about the loop diuretics?

MARVIN A. KONSTAM, MD: I think most patients in the category that we're talking about, with symptomatic heart failure are going to need loop diuretics such as furosemide in order to achieve a reasonable volume status.

ADOLPH M. HUTTER, JR., MD: Okay. Marc, is this true for both systolic and diastolic heart failure?

MARC J. SEMIGRAN, MD: Certainly it is, Dolph. I think that you need to get the patients to a volume status which they're as relatively free of symptoms as possible. Certainly, and particularly, for diastolic heart failure, diuretics are much of what we have to offer in that disease state, and it's important.

ADOLPH M. HUTTER, JR., MD: So EF is not so important. You know, 65%, 25%, get them euvolemic.

MARC J. SEMIGRAN, MD: Exactly.

ADOLPH M. HUTTER, JR., MD: Now, Lynne, what's next? Do we start with a beta blocker or do we start with an ACE inhibitor or an ARB? Where do we go next?

DR. LYNNE W. STEVENSON, MD: Well, assuming that you have the patient now at a good volume status, certainly our tradition and current practice would favor starting the ACE inhibitor first. The big difference is that we're not anymore trying to get up to a target ACE inhibitor dose before we start the beta blockers, so we're trying to get some of each on now.

ADOLPH M. HUTTER, JR., MD: So if your blood pressure's kind of low, don't push one drug too high, use both drugs?

DR. LYNNE W. STEVENSON, MD: Yes.

ADOLPH M. HUTTER, JR., MD: Do you agree with that, Marv?

MARVIN A. KONSTAM, MD: Yes, I would agree with it. I think the major message, I think, as Lynne is alluding to, is that we now have a set of drugs, ACE inhibitors and/or angiotensin receptor blockers, beta blockers, and I know we'll be talking about aldosterone blockers, that improve the natural history of the patient, and so in the case of, and so I think most of us would approach this by saying, "Let's aim to get the patient on either an ACE inhibitor or an angiotensin receptor blocker and a beta blocker in relatively short order, and titrate it up to match the patient's vital signs and volume status as we can, and move forward," as Lynne suggested.

ADOLPH M. HUTTER, JR., MD: You were mentioning a very good point, the patient's vital signs. You know, hypertension versus low tension, heart rate and things like this. Marc, ARB or ACE inhibitor? What would you start with?

MARC J. SEMIGRAN, MD: Well, I would favor starting with an ACE inhibitor and switching those patients who are intolerant of the ACE inhibitors, perhaps most commonly because of a cough, to an ARB. I think that the majority of our studies in congestive heart failure, and even in those patients that have LV dysfunction related to a prior myocardial infarction are with the ACE inhibitors. There is some good data with the ARBs, but I think that the ACE inhibitors are effective, they're less expensive, as a rule, than the ARBs, and they offer the potential additional benefit of decreasing bradykinin breakdown which could lead to increased nitric oxide levels, which may be beneficial.

ADOLPH M. HUTTER, JR., MD: What's your take on it? Do you prefer an ACE inhibitor to start with, too, Lynne?

DR. LYNNE W. STEVENSON, MD: Definitely, and not only for the reasons of the body of data, but also I tend to…

ADOLPH M. HUTTER, JR., MD: The body of data being greater for the ACE inhibitors, yes.

DR. LYNNE W. STEVENSON, MD: Greater for the ACE inhibitors. But I tend to take care of a lot of patients that are at late stages of disease, and we clearly see more hemodynamic benefit with the ACE inhibitors, probably related, as Marc suggested, to the bradykinin. You see more vasodilation with ACE inhibitors than with ARBs, at least in the late stages of disease.

ADOLPH M. HUTTER, JR., MD: That's a very good and important. Does it make any different if they have a cold nose or a wet nose?

DR. LYNNE W. STEVENSON, MD: The patient who is vasoconstricted is the patient, I think, for whom the ACE inhibitor may have particular benefit over the ARB, just from a hemodynamic standpoint, aside from the natural history issues that Marv alludes to.

ADOLPH M. HUTTER, JR., MD: So, Marv, would you start with an ACE inhibitor?

MARVIN A. KONSTAM, MD: I mostly agree. I think the nod goes to the ACE inhibitor in my mind, principally because the data are more expansive and more crystal-clear in terms of initial therapy. But I should add that, you know, just mention that both CMS and JACO have adapted their quality measure to accept either an ACE inhibitor or an ARB.

ADOLPH M. HUTTER, JR., MD: CMS and JACO, could you define that?

MARVIN A. KONSTAM, MD: Centers for Medicare and Medicaid Services and the Joint Commission for Hospital Accreditation.

ADOLPH M. HUTTER, JR., MD: There you go.

MARVIN A. KONSTAM, MD: They both established that either one is an acceptable drug for the quality measure.

ADOLPH M. HUTTER, JR., MD: But all three of you kind of lean toward ACE inhibitor. You make a good point, more data. And particularly if you're vasoconstricted, more vasodilatory effects with the ACE inhibitor, probably related to the bradykinin, which is elevated, but not with the ARBs, and of course it's the bradykinin that seems to cause the cough. So you start that way and then go to an ARB so far, in general?

DR. LYNNE W. STEVENSON, MD: Yes.

ADOLPH M. HUTTER, JR., MD: Now, when do you introduce a beta blocker? Marc, why don't you start with it? When do you start a beta blocker? And we'll talk later about which beta blocker to use, but just in general, when do you start a beta blocker?

MARC J. SEMIGRAN, MD: Well, again, certainly for the systolic dysfunction patient, we know that beta blockers do improve symptoms and do improve outcomes. I think that they may have a role in the treatment of dyschezia heart failure, but that that role is much less proven. Certainly, many patients with diastolic heart failure also have hypertension, and beta blockers are effective antihypertensives.

Staying with the systolic dysfunction patient, I start the beta blocker as soon as I have the patient relieved of their volume overload. They may not be at a normal volume status. You may have to tolerate a little bit of ankle edema in order to maintain an adequate blood pressure. But as soon as they're not volume-overloaded, I, too, start the beta blocker.

ADOLPH M. HUTTER, JR., MD: What about you, Lynne? When do you start a beta blocker?

DR. LYNNE W. STEVENSON, MD: I start the beta blocker perhaps just a tad later than Marc, because I like them actually not to have any ankle edema, and I also like to have some comfort that they're going to be able, for a few days, anyway, to maintain a normal volume status, and then I will start it, usually.

ADOLPH M. HUTTER, JR., MD: Of course, I suppose if you start a little bit early rather than stopping, you just increase your diuretic if you needed to, or would you back off on the beta blocker? If they started getting more edema or retaining fluid as you start the beta blocker, would you back off, or would you just increase the diuretic?

DR. LYNNE W. STEVENSON, MD: Usually I would back off a little bit until I have them stable again. And then I would wait a little longer next time, I think, before uptitrating.

ADOLPH M. HUTTER, JR., MD: Ratcheting up. So you'd back off, but not stop?

DR. LYNNE W. STEVENSON, MD: Right.

ADOLPH M. HUTTER, JR., MD: Okay. Marc?

MARC J. SEMIGRAN, MD: You know, I think all of us have moved toward being more aggressive to start the beta blocker earlier and earlier, and I think that although the clinical trial data are not as crystal-clear for hospitalized patients, I think most of us now would say, somebody's hospitalized with heart failure, let's try to get them on at least a small dose of a beta blocker during that hospitalization. And there are good data to indicate that if you do that, the likelihood of them being on a beta blocker, you know, a few months later is much better.

ADOLPH M. HUTTER, JR., MD: That's an excellent point, because, you know, Dr. Konstam didn't put them on a beta blocker. Maybe he doesn't need it. I mean, that message gets out to the primary care doctor. Also, I think you make the argument, if you have some sort of an untoward effect with a beta blocker, you'll find out why they're in the hospital. So I guess you could all make an argument, get them euvolemic first. You'd get them a little drier than probably other would, but maybe start a beta blocker, make sure they tolerate it, and then try to send them home, at least initially, on all three agents, a diuretic, an ACE or an ARB, probably an ACE in your case, and a beta blocker. Is that fair? Would you start them in the hospital right away, or would you be willing to wait to start the beta blocker later on?

DR. LYNNE W. STEVENSON, MD: If we look overall at the average patient hospitalized in the United States, it's with a blood pressure of about 120 with heart failure, and it's with relatively mild overall severity of disease. And I would completely agree. The average patient we would expect to send home on all three.

But there are those patients who you feel you just barely squeaked by in getting them dry and getting them recompensated, and that's the patient in whom I would want to wait a week and make sure that they're still stable.

ADOLPH M. HUTTER, JR., MD: And, unfortunately, nowadays we have to document in the chart for the heart failure patient that he didn't go home on a beta blocker because the blood pressure's still too low, or something like that. But that's the game we have to play to prove to everybody else that everybody's doing the right thing. Yes, Marc?

MARC J. SEMIGRAN, MD: Dolph, I think also to take off a little bit on Lynne's point, I think it's very important to talk with the patient and educate them as to the potential short-term volume retention that may occur with a beta blocker. Perhaps this is the time to bring in a disease management program or an outpatient contact with a nurse or nurse practitioner to help the patient realize when they may be having some volume overload related either to the initiation of the beta blocker or to the uptitration, where they would have a mechanism by which they could increase their diuretics such as to manage that.

ADOLPH M. HUTTER, JR., MD: Yes. You make a good point, Marc. You could also talk about the importance of an early follow-up after the first hospitalization so you can go over these with the patient or have a heart failure program where you can do this.

Now, which beta blocker? Marv, do you want to start out?

MARVIN A. KONSTAM, MD: Well, I think, first of all, it's important to think first about those specific drugs in any class of drugs that has actually been shown to have the benefit in a clinical trial. And in the case of beta blockers it's probably more important than in the case of ACE inhibitors, because there's a lot of variability in receptor selectivity and in associated effects varying from beta blocker to beta blocker.

So I would say the first message would be, use a beta blocker that's been demonstrated to have an outcome benefit in a clinical trial such as carvedilol, long-acting metoprolol or, rarely used in this country, but bisoprolol.

ADOLPH M. HUTTER, JR., MD: Okay. Now, between metoprolol and carvedilol there have been head-to-head trials. Which drug of those two would you prefer?

MARVIN A. KONSTAM, MD: You know, the most well-known head-to-head trial is called the COMMA trial, and it compared short-acting metoprolol to carvedilol, and the nod went to carvedilol in that trial. There are differences of interpretation of that. You know, my own is that the difference is mostly driven by dose and specific drug.

ADOLPH M. HUTTER, JR., MD: You don't think the vasodilating effect of carvedilol is an additional phenomenon?

MARVIN A. KONSTAM, MD: It could be, and certainly the vasodilation, you know, may result in symptomatic improvement and perhaps outcome effects. But you have to weigh that against what's going on with the specific patient. So, for example, if you have a patient with a marginal blood pressure whom you're trying to get on an ACE inhibitor, as well, and you're trying to get them on some beta blocker, it might be easier in some circumstance to use a more selective agent early on.

ADOLPH M. HUTTER, JR., MD: Sure, sure. Good point. You're bringing up the very important thing of individual selection for the patient's needs. Yes?

MARVIN A. KONSTAM, MD: Right.

DR. LYNNE W. STEVENSON, MD: I actually want to offer one slightly alternative viewpoint on the COMMA trial, which is that in my mind, the COMMA trial showed me that short-acting metoprolol is not too bad, and this in fact is somewhat comforting, because we all know that our colleagues across the country, in some of the settings do not have patients who can afford to take either of the brand-name beta blockers that have been tested in the trials. And so they've gone to the short-acting metoprolol, and I think that trial provides some reassurance, in fact, that that is active, that that is effective.

ADOLPH M. HUTTER, JR., MD: So when you bring cost into it, then you have a more equivocal judgment to make in terms of metoprolol versus carvedilol.

Blood pressure's good. It's 120. Cost not a problem. Do you have a preference?

DR. LYNNE W. STEVENSON, MD: If the blood pressure's 120, I would probably favor carvedilol. And the other factor I would additionally state is that if the patient has diabetes, I would favor carvedilol because of the effects on glucose tolerance.

ADOLPH M. HUTTER, JR., MD: Yes, very good point. In fact, why don't we just mention now that that study's been done also in the diabetics, metoprolol versus carvedilol, and carvedilol seemed to win that battle, too. Perhaps related to the peripheral vasodilatory effect of the drug. They don't really understand the mechanism. That's a good point. So diabetic would also lean you toward carvedilol.

MARC J. SEMIGRAN, MD: Though remember, that was a study of diabetic hypertensives.

ADOLPH M. HUTTER, JR., MD: Right.

MARC J. SEMIGRAN, MD: Not diabetic heart failure patients.

ADOLPH M. HUTTER, JR., MD: That's right. Right. Yes. Marc, do you have a preference between the two drugs?

MARC J. SEMIGRAN, MD: I would agree with what has been said previously. I think for the patient with a blood pressure of 120, then I would use carvedilol. I think that a problem with the COMMA study is that the preparation of metoprolol that was used was not the one that has been shown to be effective in heart failure.

Again, I do, I think, most of the time tend to start with carvedilol, because most of the patients do have a blood pressure that tolerates it, but that there certainly are patients that I put on long-acting metoprolol, particularly those with a borderline blood pressure or those that have bronchospasm and whom I think that the beta-1 selectivity may allow me to get them on a beta blocker where they might not otherwise tolerate it.

ADOLPH M. HUTTER, JR., MD: Okay.

DR. LYNNE W. STEVENSON, MD: I'd actually just like to say, in my population, if I look at the patients on beta blockers, I would say it's about 60% carvedilol, 40% of the long-acting metoprolol.

ADOLPH M. HUTTER, JR., MD: So you're all using both drugs. Okay, well, that's a very important point to make. And I guess we're talking about, also, blood pressure and heart rate. You've got a really good blood pressure and a pretty fast heart rate, you're going to be a little bit more aggressive with the beta blocker and get it out a little earlier. Is that fair?

MARVIN A. KONSTAM, MD: Absolutely. And we should mention dose, and I think in any of these drug selection questions, let's not forget dose, because I think one thing that's very clear with the beta blockers is there is a dose response in terms, certainly in terms of hemodynamic and heart rate effects. But also, there is evidence that there's a dose response in terms of outcome effects and effects on ejection fraction down the road. So we need to push toward target doses and watch for limitations in terms of vital signs and adverse effects, but otherwise push toward target doses.

ADOLPH M. HUTTER, JR., MD: And in carvedilol, that's 25 twice a day? Or higher?

MARVIN A. KONSTAM, MD: Yes. The doses used in the outcome studies, the U.S. carvedilol trials and the COPERNICUS study, use 25 mg twice a day of carvedilol.

ADOLPH M. HUTTER, JR., MD: Can we go higher if we have room?

DR. LYNNE W. STEVENSON, MD: Oh, yes.

ADOLPH M. HUTTER, JR., MD: So that's not the maximal dose.

DR. LYNNE W. STEVENSON, MD: But I also want to emphasize this target dose, it troubles me somewhat, because it's based on trial populations that are not entirely representative of most patients. I think a very nice practical, real-world study that was done in Cleveland demonstrated that in a heart failure clinic, when you really push, about half of the patients will get onto a target dose. So, you know, not everybody's going to get there.

ADOLPH M. HUTTER, JR., MD: We've all had patients. You know, "I just, you know, I was tolerating 12.5 twice a day, but, boy, I really felt terrible. I got more short of breath, you know, when I went up to 18.5 or 25." So you just kind of do what the individual patient lets you do.

MARC J. SEMIGRAN, MD: Right. And the kind of neat thing about the dose response trial with carvedilol is it showed efficacy at lower doses of carvedilol, and if you're not able to reach the target dose, you're still doing a good thing by having the patient…

ADOLPH M. HUTTER, JR., MD: Right. And as you said before, try to have an ACEI with a beta blocker. I want to move on to another area now. And what about the aldosterone inhibitors? What's their role?

MARVIN A. KONSTAM, MD: Well, aldosterone inhibitors are still another class of drugs, after we've talked about the ACE inhibitors, the ARBs and the beta blockers, and there are two studies in different populations that indicate that use of an aldosterone blocker compared to placebo reduces mortality. The two groups of patients are the patients who are either New York Heart Association Class IV or recently Class IV. That's the RALES study. Or the post-MI population, that's the EPHESUS study. And in both of those cases on top of background therapy there was a reduction in mortality.

So we are using them, I think most people are using them more and more aggressively, with the caveat that you have to know what you're doing. You have to monitor electrolytes and potassium, because used glibly or without proper monitoring, you definitely can get into trouble with hyperkalemia.

ADOLPH M. HUTTER, JR., MD: Right, so you have to watch that. Do you have a preference of the two? What are the two agents that are used now?

MARVIN A. KONSTAM, MD: So, old-fashioned spironolactone, or newfangled eplerenone. And, frankly…

ADOLPH M. HUTTER, JR., MD: Newfangled and more expensive.

MARVIN A. KONSTAM, MD: More expensive. And frankly, the differential between the two is not -- not crystal-clear. One was used in one study, another in the other study. So one could go that route of picking and choosing based on a particular study. You know, I think my own feeling is they're probably pretty interchangeable. There is some difference in the side effect profile. Gynecomastia does occur in about 9 or 10% of males with spironolactone. It does not appear to recur with eplerenone.

ADOLPH M. HUTTER, JR., MD: Marc, which one of those agents would you start with?

MARC J. SEMIGRAN, MD: I almost universally start with spironolactone.

ADOLPH M. HUTTER, JR., MD: Yes, then if they get gynecomastia in a male…

MARC J. SEMIGRAN, MD: And if the side effects of… Yes, I would. And just a little bit to add. The RALES study, while you had to be class IV at some time within the prior six months to study entry, the majority of the patients, I think, were actually class III at study entry. And I think that, you know, I've used this as a basis to expand my use of aldosterone-blocking agents to a large portion of the people that I see with heart failure that are symptomatic.

ADOLPH M. HUTTER, JR., MD: Class III. How about earlier? Lynne, go ahead.

DR. LYNNE W. STEVENSON, MD: I really want to emphasize, because, you know, we live in a pretty fortunate environment where we do research studies, we have nurses who call our patients, we have very good ways of checking a lab all the time. This gets much harder out in a general practice to monitor the potassium often enough to prevent hyperkalemia. And, you know, the community studies have been quite concerning, that potassium levels and renal function are not being monitored well enough in this study.

ADOLPH M. HUTTER, JR., MD: Now, I'm glad you threw in renal function, too, because we can get these people too dry, and then their potassium could really shoot up, also.

DR. LYNNE W. STEVENSON, MD: So I think the caveat is that if you can't monitor these patients closely, either because of the limitations of the practice setting or because of limitations of the patient, they just don't come back and get their blood drawn, then I think it's probably best not to start this drug.

MARVIN A. KONSTAM, MD: I might say, I take your point, but I might say it slightly differently than that myself, because I think that with any drug, and I think with the case of the aldosterone blockers, the point is really clear, electrolytes need to be monitored.

Having said that, you know, I can dial back to the mid-1980s, where we were just beginning to use ACE inhibitors, and the view was that these were dangerous drugs that should be used only as, you know, third- or fourth-line therapy for hypertension, under certain, select circumstances because they were dangerous. And I think practitioners learned to use them and learned to monitor kidney function in electrolytes. I think patients need to be monitored and people need to know how to use these drugs.

ADOLPH M. HUTTER, JR., MD: So I think you're all saying, it is a great class of drugs. We ought to get them on board. Probably after we have them euvolemic, we've got them on a ACE inhibitor, we've got them on a beta blocker, then put this on board, monitor them closely, maybe start with a cheaper one then go to the more expensive one if you have side effects.

ADOLPH M. HUTTER, JR., MD: Now, there's another class of drugs. That's the combination of nitrates and hydralazine. We had this recent study, the A-HeFT trial, done in blacks, self-described blacks, who had class III and class IV heart failure, decreased mortality. But what is the group's take on that drug? Should we use it? Should we use it only in blacks? What's the scoop?

DR. LYNNE W. STEVENSON, MD: I think it's important to realize that in fact we've been using it for a long time. Hydralazine and nitrates are a combination that we use in patients, particularly those who have trouble with ACE inhibitors. And also, to separate them for a moment, nitrates are often used in addition to ACE inhibitors as well. So I think this is a very potent combination of drugs, and the nitrates by themselves are also potent.

ADOLPH M. HUTTER, JR., MD: And, of course, they certainly improve symptoms, don't they? I mean, they cause venodilatation. I mean, they decrease congestive symptoms. What about the effect on mortality? Well, first of all, how do you guys use those drugs?

MARVIN A. KONSTAM, MD: Well, I think, as Lynne points out, the information dates back to the '80s. In fact, the V-HeFT study was the first real outcomes study that we had.

So I think certainly in the black population, I think the A-HeFT study provides very good data that to achieve additional mortality benefit and outcome benefit and quality of life benefit, over and above very good background therapy, including ACE inhibitors and beta blockers and, in many cases, aldosterone blockers. So certainly, in the African-American population, I think practitioners really should be moving to this combination.

We know less about hard data in the non-African-American population. Certainly, we should be thinking about the combination of hydralazine and a nitrate in patients who are intolerant of both an ACE inhibitor and an angiotensin receptor blocker.

ADOLPH M. HUTTER, JR., MD: Marc?

MARC J. SEMIGRAN, MD: And I do. I do feel there is compelling mortality evidence in African Americans to adding isosorbide and hydralazine to their regimen. But in a patient who's not African-American who, perhaps, is not doing as well as I would like and who I think vasoconstriction is playing an important role, I will add those agents to the ACEI, and certainly to the ACE and beta blocker combination.

ADOLPH M. HUTTER, JR., MD: Though if you had a borderline blood pressure on an ACEI and a beta blocker, and, I suppose, in a black person, would you, say, back off on the other drugs to get this combination on board? And if so, would you do the same thing in a non-black person? Anybody?

MARVIN A. KONSTAM, MD: Well, I think it's very important to say we don't know, really, whether there's a difference, different response between blacks and non-blacks.

ADOLPH M. HUTTER, JR., MD: Good point, very good point, because it was only studied in blacks. It wasn't studied in whites per se.

MARVIN A. KONSTAM, MD: Right, right. We have the data in blacks, so we have to sort of say it, make sure that we make that distinction. You know, I think, as my colleagues have said, I think there's compelling evidence that using this combination on top of standard therapy in blacks has a mortality and other benefit, and so I think one should make an effort to get the patient on it.

ADOLPH M. HUTTER, JR., MD: And even if you have to back off a little bit, try to get all the agents on board in the black person.

MARC J. SEMIGRAN, MD: We know from some re-analyses of ACE inhibitor data in blacks that they don't get as much of a mortality benefit as in Caucasians.

ADOLPH M. HUTTER, JR., MD: Yes.

MARC J. SEMIGRAN, MD: So I think, again, there, you know, the compelling evidence to use isosorbide and hydralazine, even if the ACE inhibitor dose has to come down.

ADOLPH M. HUTTER, JR., MD: Okay. Lynne, would you try to get it all on board?

DR. LYNNE W. STEVENSON, MD: That's a really difficult question, because…

ADOLPH M. HUTTER, JR., MD: That's why I asked you guys.

DR. LYNNE W. STEVENSON, MD: I'd have to look at what are the symptoms that are really troubling the patient.

ADOLPH M. HUTTER, JR., MD: Okay.

DR. LYNNE W. STEVENSON, MD: If the symptoms are related to dyspnea on exertion, then I would try to get them all on. If, on the other hand, I keep getting stuck with refractory fluid retention, then I'd need to look very carefully at why that's happening, and I'm not sure hydralazine would help that. So as soon as we talk about the patient whose symptoms aren't responding, then we need to really individualize how we look at the patient, say what symptom isn't responding and what's limiting me.

ADOLPH M. HUTTER, JR., MD: Is it congestion, or is it a poor output type thing.

ADOLPH M. HUTTER, JR., MD: Well, this has been a great discussion about stage C heart failure and a very great and practical discussion about the use of the various drugs we have to treat this problem. Thank you all very much.

DR. LYNNE W. STEVENSON, MD: Thank you.

MARVIN A. KONSTAM, MD: Thank you.

ADOLPH M. HUTTER, JR., MD: And thank you for joining me. I'm Dolph Hutter.

Related References/Reading:

Hunt SA and the Writing Committee Members. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. 1-82.

Taylor AL et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. N Engl J Med. 2004;351:2049-2057.