Emerging Evidence to Guide Patient-Centric Treatment Selection for Heart Failure - Episode 9

Implementation and Continuation of Guideline-Directed Medical Therapy (GDMT) in Heart Failure

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Javed Butler, MD, MPH, MBA, comments on implementing, continuing or cutting back on quadruple therapy after patient’s cardiac function has improved.

James Januzzi, MD: Muthiah, as a co-director in the Cardiometabolic Implementation Center [Harvard Medical School], implementation, something that a lot of clinical trials don't often think about. We identify these great therapies and it's all about getting them in the right patient at the right time. You said earlier how prevention of hospitalization is so critically important to reduce the future risk. What are your thoughts about this concept of in-hospital initiation, and what can be done to improve it?

Muthiah Vaduganathan, MD, MPH: It's really the million-dollar question. In many ways, across any discipline of medicine, we've seen perhaps the greatest gains in survival if medical therapies are implemented in the space of heart failure. That's a wonderful success story. Unfortunately, it's estimated that it takes up to 17 years for a new drug therapy to be implemented. The heart failure hospitalization is a critical, critical opportunity in which we have a so-called captive audience. We have a patient who is at risk, who's vulnerable, who is meeting a number of clinicians, where the patient can be educated not only about their disease process and their disease trajectory and prognosis, but also about available medical therapy options. Furthermore, those therapies, especially combination medical therapies, can be implemented during even [that] short hospital stay. Initial tolerability, initial hemodynamic assessment, initial electrolyte and kidney function assessment, can be done in the hospital. Furthermore, we can leverage resources that are unique to the hospital setting.

James Januzzi, MD: Like what? I'm curious.

Muthiah Vaduganathan, MD, MPH: We have case managers and clinical pharmacists who can assist patients in gaining access to critical medications because medication use and adherence is not only something that is determined by the patient. We now know that there are a number of societal determinants that critically influence if a patient ultimately can afford access and take long-term medication.

James Januzzi, MD: That's a wonderful point that, again, we learned in medical school how to write a prescription, but we don't sometimes think about the ramifications of what if the drug is high cost or can't be obtained easily. In addition, we have evolving technologies that may help us to identify eligible patients. Can you tell us a little bit about what has been done at the Brigham and Women's Hospital with respect to finding these patients because they're everywhere in the hospital?

Muthiah Vaduganathan, MD, MPH: Absolutely. Heart failure reaches across, again, all medical specialties. While many are under the care of cardiologists and even heart failure specialists, the majority are under the care of primary care doctors and, in the hospital settings, hospitalists and other specialists. At Brigham and Women's Hospital, we've incorporated in our electronic health record system a query system that attempts to actually identify prospectively, on a daily basis, all patients who are admitted to the hospital with a primary or secondary diagnosis of heart failure. This allows us to rapidly implement quality improvement strategies to improve the uptake and adherence of medical therapies.

James Januzzi, MD: It's so very important, as you've heard, that initiation in the hospital really should be a priority, and we now have safety data for all 4 classes of the main therapies for reduced ejection fraction, showing safety, and in many cases, efficacy. More importantly, though, while the drugs clearly are effective, not only in reducing short-term risk after hospitalization, it gets them in place for the longer term. Why is hospitalization-based prescription so important? Two important results to discuss. The first are data from the get-with-the-guidelines. Steve Green from Duke University showed that the best predictor of never receiving guideline-directed medical therapy in somebody who was discharged from the hospital is not having received it in the hospital. Secondly, Tariq Ahmad, MD, MPH, Yale School of Medicine, also a Duke alum, showed some data that in-hospital initiation of quadruple therapy in a modeling analysis was associated with a number needed to treat of only 4 patients to reduce a mortality event. These are just incredibly compelling results that show how important it is, not just from an efficiency perspective, but also for our quality and quantity of life perspective, for our patients. So we have our patients on quadruple therapy. Titration can be done in the office-based setting, and we're going to discuss this maybe. Before we do, let's fast forward to the good news, which is that these therapies help our patients feel better and often improve heart function, quality of life, et cetera. So Javed, you're seeing a patient in the office. They've developed what we call reverse remodeling. Their heart function is improved. They're feeling great, their ejection fraction is normal. They ask you, “Dr Butler, I'm on these 4 pills, can I stop taking them?”

Javed Butler, MD, MPH, MBA: That question is a tough one and requires some individualization. There was this long debate that we had that if somebody's heart function becomes normal, do they not have heart failure? And should we stop the medication? Or is it normal because of the medications? And if you were to stop the medications, that things would go worse. I think there are at least 2 lines of evidence that would suggest that stopping the medication is not a good idea. There was a trial, a smaller trial done called TRED-HF. People got normalized, were doing well, and they started cutting back on the guideline-driven medical therapy. Guess what? People became symptomatic and the EF [ejection fraction] started slipping down. If the EF slips down, this is not a yo-yo that then you restart and it'll come right back up. There are some serious dangers. That's one line of evidence. Second, there was this trial, DELIVER, with dapagliflozin where there was a sizable, about 20% of the population. This was a HFpEF [heart failure with preserved ejection fraction] study, but they included patients with heart failure and improved ejection fraction. Those patients who used to have EF less than 40%, but now, or greater than 40%, were included, a sizable proportion of those patients had actually normalized ejection fractions. So, not mildly reduced, but just normalized. Again, there were substantial benefits with the use of SGLT2 inhibitors. The general answer is that this is lifelong therapy, and that we should think of it like that. Now, the reason why I hesitated giving this answer right away is that at the end of the day, we are clinicians and we need to use our best clinical judgment. If there's a 45-year-old patient who developed ischemic cardiomyopathy, I'm completely comfortable making it a lifelong therapy. Now, if you have a 20-year-old female with postpartum cardiomyopathy or an 18-year-old kid with myocarditis who completely recovers, that's the patient for whom I think we should individualize it and maybe cut back very slowly, monitor their cardiac status very carefully. There are some cases where you might want to individualize, but by and large, please don't stop the therapy.

James Januzzi, MD: It’s so important to emphasize the need for continuation, even in those circumstances where you think you have a reversible cause such as atrial flutter at a high rate for several weeks, peripartum cardiomyopathy, and alcoholic cardiomyopathy. The more you do this, the more you recognize that those people probably have a 2 hit situation where they have an underlying mutation in the sarcomeric gene or something promoting their risk for cardiomyopathy. So, even though, through the wonderful therapies that we have, their heart function improves, I sometimes feel like it's a tightrope act to decide whether or not to stop. In my own clinical practice, regarding peripartum cardiomyopathy, if we see complete recovery and the mother is interested in breastfeeding, for example, I'll make changes if the intent is there and the cardiac function is improved. But in many cases, particularly to the extent that these patients often have risk factors like hypertension, justifying the continuation of these therapies, I'll continue them. In my practice, the one completely reversible cardiomyopathy that I will stop GDMT [guideline-directed medical therapy] on is stress cardiomyopathy like Takotsubo syndrome. Javed, what are your thoughts there, since I gave you that counterpoint?

Javed Butler, MD, MPH, MBA: I completely agree with you. That actually tells us about our own bias, that if we find, or if we assign a cause, that doesn't mean that that's the only cause. You specifically point out peripartum cardiomyopathy, that there are data, that there may be underlying genetic predisposition for those patients. Basically there's maybe a ton of patients, people walking around with those mutations, but they don't go into heart failure till they have something that challenges that reserve. But that underlying abnormality does not go away. So, again, looking at it from a broader perspective is really important.

Transcript edited for clarity