Dr. Ferdinand: There have been some small studies looking at pharmacogenomics specifically in self-identified blacks showing some single nucleotide polymorphisms related to beta receptors and showing less response based on that. I’m certainly not making the case that we shouldn’t offer morbidity/mortality-proven drugs to anyone regardless of self-identified race, ethnicity, age, or sex, but I was pointing out that in the landmark studies, we often under-represent certain subpopulations and I’m always a little bit cautious with extrapolation of data.
Dr. Smart: I agree.
Dr. Ferdinand: So that brings us to other pharmacologic options and again, we are going to revisit the conventional medications, including the ACE inhibitors, the ARBs, and the aldosterone antagonists, but before we do that, is there anything else specifically as it relates to treating self-identified black patients we should discuss, Chris?
Dr. Leggett: Certainly, in the context of the current therapies that we have discussed, without introducing new therapies, such as the fixed dose combination hydralazine and isosorbide dinitrate (BiDiL®), I think that our biggest hindrance in achieving therapeutic success with our patients is not the lack of available therapeutic options, but rather, often, poor patient adherence, combined with our collective inability to simplify their dosing regimens and persistently pursuing basic clinical and pharmacogenomics research trials to better understand every aspect of the disease process.
Dr. Piña: I just came from the in-patient service and it is hard to get patients to take so many pills. We always say, “Oh, the patient is not adherent.” But I really think that we have a responsibility to try to find a regimen that they are more likely to be adherent to by reviewing their medications at each visit and removing drugs that are not necessary. Sometimes we add medications to handle side effects of other drugs. In the case of hypertensive patients, we keep adding drugs before we even optimize one of them. Even though I’m not a big combination pill prescriber, very often for these patients with severe hypertension, the combination of an ACE or an ARB with a hydrochlorothiazide-like drug, in one pill, may improve adherence. So rather than always pointing the finger at the patient, I think we have to find techniques to get them engaged and make their regimen a lot easier for them, with education as to why they’re taking what they're taking. And, when we have the opportunity to remove drugs, try to leave them with those that are most essential.
Dr. Ferdinand: There have been some data from the American College of Cardiology’s PINNACLE Registry along with the American Heart Association’s guidelines programs where they specifically examine registries of electronic health records and subsequently provide report cards to providers and inpatient facilities, pointing out gaps in the application of evidence-based medications for HF or post-myocardial infarction. For instance, data reports appropriate use of ACE inhibitors, or ARBs if not tolerated, or beta-blockers or aspirin. There does appear to be an ability to close some of those gaps when those data are available. Do you think going forward, Chris, that’s going to be a way to decrease some of these disparities in the application of evidence-based medicine?
Dr. Leggett: Yes, I absolutely think that will be helpful in guiding clinicians and other health care professionals to adhere to guideline-based HF therapies, which have the collateral benefit of helping to reduce racial, ethnic, and gender disparities in access to evidence-based proven medications and life saving technologies. We may need an added layer of electronic health record trained personnel to note data in the medical record so the clinician can remain engaged with the patient. This approach should be effective in both the inpatient and outpatient setting. This will almost certainly reduce the component of racial, ethnic, and gender disparity in access to appropriate care related to physician bias.
Dr. Ferdinand: Frank, you’ve had a wealth of experience in the field of HF, and I know working and living in Louisiana you treat a lot of high-risk patients of all races including blacks. Are there any clinical pearls that you would like to add to Ileana and Chris’s concept that we need to do more to increase adherence to medications?
Dr. Smart: Keith, it is the Achilles’ heel of what we do, as you well know. I can sit there and write prescriptions all day long, and if people don’t get them filled, then it doesn’t help them. Because of the cost of medications, particularly for the population that we have here in Louisiana with a very high self-pay and Medicaid rate, those patients are tough to take care of. You have to factor cost into your pharmacologic choice all the time. We have to recommend low-salt diets and low-fat diets to these patients, but that’s not necessarily similar to what the normal diet for the rest of the family is and it becomes a major lifestyle shift for some of our patients.
Yes, it’s a big problem. I wish I had pearls to make it better. I think that the problem with adherence is that everybody has their own individual issue and you have to speak to them. I think that my patients who are of a different race/ethnicity do not trust me as much when we first meet. I have to earn their trust a little bit more than I do with some of my Caucasian patients. Maybe that’s just historic. I don’t really know. It may be that I don’t come across as well as I should but I think that those are things that enter into a decision process, when you’re trying to talk to people to take an extra couple of minutes and explain things a little bit more as opposed to just dashing out of the room.
Dr. Ferdinand: You know, Frank, the social scientists have a term for that. It’s called cultural humility, understanding that there may be barriers in our communication methods to persons of various backgrounds, many of whom may have limited literacy or have cultural values related to medication use, diet, and exercise that may be different from our own. The practitioner always needs to take the time to sit down at eye level and listen to that patient. When you provide instructions, give them an idea of what they think you’ve said versus mumbling something and scribbling it on a prescription pad and say, take this to the pharmacy. Would you agree with that?
Dr. Smart: Absolutely.
Dr. Ferdinand: So let’s go back to Chris. Would you like to add anything?
Dr. Leggett: Yes, it’s an interesting dialogue because there is an automatic assumption that because you are of the same race/ethnicity that there are no communication problems and that you understand each other just because of your genetic racial/ethnic background similarities. There are so many layers to race and/or ethnicity that are economic, social, and environmental, which clearly play a central role in that communication process. So I do agree that taking the extra minute, while challenging, to sit down and maybe put your hand on their back, and look into their eye and connect with them as a human being, often yields more towards compliance than anything that you ever write down on a prescription pad. I believe that the time performance pressures that we all experience in modern-day clinical practice minimizes those important touchy-feely interactions, and the majority of our patient interaction is now becoming computer-based.
Dr. Ferdinand: There have been increasing reports of patient dissatisfaction with clinicians who sit at a computer and type into an electronic health record with their backs to the patient.
Dr. Leggett: Absolutely, and it’s increasingly becoming part of our culture. I was reading in one of the cardiology journals about how handheld devices are going to become such an inseparable dimension of our lives with patient interaction, that we’re going to be constantly entering data. Those data that we’re entering, while useful, are going to take our eyes off the patient.
Dr. Ferdinand: Those are all very good points. I’m going to loop back to the pharmacologic management because we do have some additional outcome data in a self-identified black patient population. That was the African American Heart Failure Trial (A-HeFT) and I was one of the steering committee members and an investigator at two sites.12 But before I give my opinion, Chris, do you want to give us any of your take on the background of A-HeFT and what it was all about?
Dr. Leggett: A-HeFT was an opportunity to examine the therapeutic benefit of a fixed dose combination of hydralazine and isosorbide dinitrate on class 3 and 4 HF patients of a self-identified black population on standard therapy. It also allowed for an increased representation of women in the trial. This trial provided a clinical opportunity to make more specific comments about whether a particular therapy worked or didn’t work and whether there was a survival, hospitalization, or quality of life benefit. I think beforehand, as you stated earlier, that we just simply did not have that sort of representation in many of the older trials that we’ve relied heavily on.
We have slowly learned that all medication therapies for a particular illness do not clinically provide the same benefit across racial/ethnic and gender lines. There are genetic, biologic, and metabolic factors that contribute to how our bodies absorb, metabolize, and utilize medications. The scientific opportunity to increase our clinical understanding and search for added therapeutic survival and quality of life benefit in African American men and women with HF was hugely important.
DR. FERDINAND: Chris, I agree and hold the same opinions regarding the benefits of the A-HeFT trial. The reason for these positive findings are unclear and perhaps, in blacks, less nitric oxide availability and increased endothelial dysfunction. We should note the A-HeFT trial was stopped early because of a significant and clear mortality benefit.
Dr. Piña: The A-HeFT trial did a good job including women, and in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION),13 as many as 35% women in my center, so it can be done. Getting women to consent may take a little bit longer. I don’t have women consent unless either the significant other or the family are in the room, to give the family full understanding of the trial rather than being relayed through the patient, where often the family will say, “Oh no, mom, you’re going to be a guinea pig—don’t get into that trial.” So I think there are different sensitivities to the different gender approaches and care that would help. Providing the appropriate and factual information about the trial to both the woman patient and the family can be rewarding.
Dr. Ferdinand: That brings us to the next point, and I’ll give some of the data as the background. We’ve already introduced A-HeFT.14 This was based on some subgroup analyses in earlier studies, the Vasodilator-Heart Failure Trial I (V-HeFT-I)14 and Vasodilator-Heart Failure Trial II (V-HeFT-II),15 where black patients appeared to have a benefit with the combination of isosorbide dinitrate, a vasodilating drug and a nitric oxide donor, and hydralazine, an arterial vasodilator, which also has antioxidant properties.16 Our purpose was to study a self-identified black population and to see whether there would be a benefit when conventional therapy was added in patients with New York Heart Association class III and IV.
The primary endpoint was a combination of mortality, hospitalization, and quality of life, and 1050 black patients were entered into the study. As I already pointed out, approximately half of them were women and we did, indeed, show an outcome that was beneficial—a survival increase of 43% with the combination of isosorbide dinitrate added to conventional therapy,14 33% reduction in the rate of first hospitalization for HF16 and significant improvement in quality of life, based on the Minnesota Living with HF Questionnaire. The theoretical background was that it may be more than just a hemodynamic effect; it may be related to nitric oxide enhancement therapy by giving the isosorbide dinitrate and an antioxidant effect by giving the hydralazine. That, of course, is unproven.
So we’ll start with Frank, then we’ll go to Chris, and Ileana. What’s your take on A-HeFT and its application to treating HF in black patients?
Dr. Smart: As you described, Keith, it is very challenging to find any fault with the study. It was well done and I think that I certainly believe that in those self-identified blacks the use of hydralazine and isosorbide dinitrate as an adjunct once they’re on the other big three, if you will, is very much indicated. The only problem is in patients with really bad HF where their systolic performance was quite low, it may become challenging from a blood pressure standpoint—in dropping the blood pressure too much. But in those patients who have reasonably good blood pressure, I think it’s very appropriate and I use it routinely.
Dr. Ferdinand: You would suggest that if we use that combination of drugs, we should start slow, especially in patients with low systolic blood pressure, to avoid excessive hypotension and dizziness.