Dr. Smart: Absolutely. I think we underplay, particularly in the HF community, how important blood pressure and feeling bad is. The other thing that we typically don’t do is talk to
our patients enough about the effects of their medications on the way they feel and when they should be taken. We talked about adherence before, but many times patients will take isosorbide
dinitrate, hydralazine, carvedilol, and lisinopril together and 2 hours later, they feel like they’ve been hit by a
bus. Just by spacing the drugs out
over the course of the day and avoiding that pharmacologic peak of all of them at the same time is important in managing people.
Dr. Ferdinand: Yes. Those are good observations. Nevertheless, there are data that A-HeFT patients with low systolic blood pressure <100 mm Hg did well on the fixed dose isosorbide dinitrate/hydralazine, and overall was well-tolerated, even with some increase in blood pressure in these patients on this medication.17 Chris, what’s your take on A-HeFT?
Dr. Leggett: I think that the 43% survival improvement and 39% reduction in the risk of a first hospitalization is huge. Another, and more global, benefit is that we’ve taken the opportunity to really try and identify a specific population of people to see if the therapy would be useful in that population. After the results were published, many discussions occurred surrounding the study design and whether it was race specific, to the point where it excluded other races and ethnicities from potential study benefit. The reality is that it was an opportunity to really focus on underrepresented study populations with a high prevalence of HF disease to see whether a survival, hospitalization, or quality of life benefit could be achieved with an added therapeutic combination to standard therapy. The benefit was clearly desirable. With that said, I am happy that a relevant HF study of a self-identified black population, with an increased representation of women, was performed. I’m also delighted that significant survival and hospitalization benefit was realized with added therapy.18
I am always of the mindset that we need to appropriately maximize our medical and technologic armamentarium as much as possible so that we can look in that therapeutic treasure chest for every patient who walks in our room. The appropriate therapies coupled with knowledgeable clinicians and motivated compliant patients will give our patients the best opportunity for improved survival, fewer hospitalizations, and a better quality of life.
Dr. Ferdinand: Ileana, any different comments related to A-HeFT?
Dr. Piña: Yes, my concerns have always been, as we’ve discussed before, with adherence, the difficulty for patients to take two additional pills three times a day, and cost of medication. How can we get twice a day dosing? Because if I can convince them at least to take a pill in the morning and take another one in the evening, we may be able to get the full dosage. It’s really a shame if adherence is part of the problem. In addition, I don’t think the usage is being appropriately recommended; the gap is huge. But we really need to push the pharmaceutical industry a bit to come up with different formulations that would make it easier to take, because reduction in mortality of 43% is significant and not seen in other HF trials.
Dr. Ferdinand: In those clinicians and researchers involved with the early investigation of the use of fixed dose ISDN/HYD, we did entertain having a longer-acting fixed-dosed combination, but it was curtailed perhaps because of some of the problems related to the uptake of the agent and the availability. The other thing is that none of the main investigators, whom I know personally, had really intended it to be limited only to black patients, although that was done at the direction of the FDA. At the present time, the Food and Drug Administration indication tends to limit it to that population, and even the Heart Failure Society recommendations describe the combination of fixed-dose isosorbide dinitrate for self-described black patients.
That brings us to the last topic, and I would like some real pointed discussion related to performance measures. The American College of Cardiology Foundation, the American Heart Association, and the American Medical Association have performance measures.19 In the past, they didn’t list the application of isosorbide dinitrate and hydralazine in self-identified blacks. Any take on that and why that is?
Dr. Piña: I was on the writing committee for the upcoming 2012 performance measures. A measure to add the vasodilator combination was strongly considered and discussed extensively. However, the definition of the denominator, i.e., racial data, would be difficult given the current status of racial data collection in most practices. The advent of electronic health systems should improve markedly the racial and ethnic data fields making this measurement achievable. It was very strongly supported around the table, nonetheless.
Dr. Ferdinand: So you believe that a fixed-dose combination of isosorbide dinitrate/hydralizine should be listed in terms of the application of a performance measure post hospitalization in the future with electronic health records? Do you think that will give us even more impetus for the use of this since it does decrease hospitalization, which, as you know, would be a cost issue for integrated health systems if patients come back within 30 days?
Dr. Piña: Yes, absolutely. We dropped the measure of discharge instructions. A new and more meaningful performance measure is an outpatient visit scheduled at discharge, and reads: “Post discharge appointment for HF patients. No measure for 2005.” This visit post-hospitalization should occur at 7 to 10 days after a hospitalization for HF, and is a wonderful opportunity to go over all the medications again, and if the patient has not had this combination added, that’s a good time to do so. That appointment can also be modified to include more patient education and once again try to engage patient adherence. The use of combination vasodilator therapy needs patient agreement and adherence.
Dr. Ferdinand: I would like to make one point that’s often mistaken by clinicians. Again, as a person who helped with the design of the trial, we wanted to have patients taking conventional medicines and the misgivings about the under-representation of blacks in landmark studies were understood. Still, if you look at the data, 69% of patients were taking ACE inhibitors and 17% were taking ARBs.16 So we did use the appropriate medications. I still think regardless of race, ethnicity, sex, or age, we should try to use those medications that are shown to be beneficial in the evidence-based outcome studies. That being said, we do know specifically in the HF population, the addition of the fixed dose of isosorbide dinitrate and hydralazine gave clear benefit, and the benefit was not only in terms of hospitalization and quality of life, but overall all-cause mortality. Although clinicians attempt to replicate dosages of the individual medications hydralzine and isosorbide dinitrate, the Food and Drug Administration has clearly indicated based upon pharmacokenetic studies, that there is no therapeutic substitute for the fixed-dose combination isosorbide dinitrate/hydralazine.
So we’ll go around the table for parting comments. I’ll let Ileana go first and then I’ll let Frank go, the two HF specialists, and Chris, since you are a practicing clinician who sees a lot of high-risk patients. I would like you to conclude.
Dr. Piña: My take-home message is that we have a lot of medications in our current armamentarium. Now we also have devices such as cardiac resynchronization therapy and implantable-cardioverter defibrillators (ICDs). We really need to start using approaches where we have the evidence and where we have the data. To simply say, my patients are not like the ones in the trials, is really not acceptable, and we need to continue to utilize evidence-based therapies for all patients to further close this gap that exists.
Dr. Smart: I will echo what Ileana said, that we need to apply the therapies that we know work. We did not talk about device therapy and, in particular, ICD therapy, and in my population here in Louisiana, I can tell you that blacks are not being implanted with ICDs at the same rate as their Caucasian counterparts.20
So there is a disparity, and in women as well. We need to eliminate those differences and have, if you would, a check sheet or a thought process of “Did I look at this; did I consider this?” in every person, whether it’s an actual sheet or something in our mind when we see somebody in the clinic and make sure that we’ve covered all the bases. Because I think that it is, as Ileana said, infinitely important to the well being of our patients.
Dr. Ferdinand: Frank, does that disparity in the use of devices and technology extend to very costly interventions such as left ventricular assist devices (LVADs)?
Dr. Smart: I don’t know the specific data on LVADs, Keith. I do know that we have looked at ICDs. We have a study that’s currently ongoing to look at cultural bias and race bias in ICD applications.
Dr. Ferdinand: Okay. Chris, last comments.
Dr. Leggett: Certain educational initiatives have focused on the areas of community education, healthcare professional education, and adherence to guidelines, and specifically on the issue of a gap in access to care, whether it’s ICD therapy, interventional therapy, or cardiac surgery. What we’re seeing is a 30% less likelihood of minorities, blacks and Hispanics, and women of all races, to have access to these technologies. There are many factors that contribute to this disparity, such as physician bias, lack of cultural competence, lack of insurance, poor economics, and decreased access to informed knowledgeable providers with readily available access to life saving therapies and technologies. As clinicians, we must minimize our learned and inherent biases, simplify patient medication regimens, follow evidence based guidelines, improve our cultural sensitivity and competence, and remember that all men are created equal and therefore deserving of excellent appropriate therapy for their condition irrespective of race, ethnicity, or gender. We must explore all avenues to improve patient compliance, as our best therapies are only as good as our patients, understanding of the personal benefit of the medication or technology to them.
Dr. Ferdinand: I’d like to thank Dr. Christopher Leggett, Dr. Frank W. Smart, and Dr. Ileana Piña for their very insightful comments as they relate to HF treatment. We didn’t just discuss treatment and identification and increasing outcomes specifically in self-identified black patients, but for all patients. HF morbidity mortality is higher in US blacks. A significant component of this disparity is driven by underutilization of evidence-based medications and devices where evidence regarding positive outcomes is available. Some of it affected by socioeconomic status, some by ability to afford medications, and then even some by mistrust of conventional providers caused by cultural barriers.
I’ve also noted that minorities, along with the elderly and women, have in the past been under-represented in HF trials and we make assumptions of efficacy often based on limited clinical data. A-HeFT gives us an excellent opportunity to apply evidence-based medicine in self-identified blacks already on conventional treatment including ACE inhibitors, ARBs, beta-blockers, aldosterone antagonists, and diuretics if needed for symptoms, with a fixed-dose combination of isosorbide dinitrate and hydralazine. Nevertheless, in order to curtail the epidemic of HF and the disparities in cardiovascular death and disability, it’s going to take the recognition and the early treatment of risk factors such as hypertension, diabetes, dyslipidemia, smoking, physical inactivity, and obesity, because that is going to be the only way we’re going to be able to prevent HF in the future.
I thank all of the faculty for their participation.