Video
Medical experts discuss benefits of titrating therapies for management of ejection fraction pathologies.
Ryan Haumschild, PharmD, MS, MBA: Dr Anderson, I’d like to start with you. We’ve talked about guideline recommendations. Can you briefly discuss some of the real-world differences in the treatment approaches of heart failure with reduced ejection fraction and preserved ejection fraction? In practice, does the treatment sequencing differ between these patient populations? How do you go about your recommendations and treatment plans for each of these?
John E. Anderson, MD: As all of our panelists have mentioned, people who have reduced ejection fraction tend to have multiple comorbidities, such as type 2 diabetes, obstructive sleep apnea, obesity, COPD [chronic obstructive pulmonary disease], or depression. We’re trying to treat all of these. Frequently, the patients with reduced ejection fraction—at least in my experience—may have already had their first hospitalization, so they’re much more involved with cardiologists. A lot of these patients with markedly reduced ejection fractions have had devices installed. A lot of them have atrial fibrillation. They mostly have an ischemic substrate.
These patients are very sick, and it’s incredibly important that there be communication between the hospitalist, cardiologist, and primary care provider because that handoff is important. I can’t tell you how many times the first person they come to is me—even before the cardiologist—having had a heart failure hospitalization. They bring their discharge summaries and they say, “Why am I not on lisinopril anymore? What is this medication? How come I’m not on metoprolol anymore? Why did they take me off of Lasix?”
In primary care, we have to be good at that handoff and working with colleagues. It’s no longer good enough to only send a message through an electronic medical record. It’s incumbent upon us to pick up the phone and talk to each other when we have those transitions and work actively with cardiologists and hospitalists. As I said before, the patients with preserved ejection fraction tend to be a little older in my practice. They tend to be a little more subtle. We do a poorer job of finding those people early, but they have just as much risk for hospitalization. In the real world, there’s a bit of difference.
As far as sequencing, a lot of times when there’s an ARNI [angiotensin receptor-neprilysin inhibitor], a change in beta blockade, the initiation of an MRA [mineralocorticoid receptor antagonist], a lot of that happens at the hospital. However, what I’ve found is that SGLT2 inhibition tends to fall into the outpatient category, and those of us who treat diabetes and are in primary care tend to be the people starting SGLT2 inhibitors first. I haven’t seen that nearly [as often] incorporated in the discharge summaries as our patients emerge from the hospital. I’d be happy to hear what other people are noticing as well.
Ryan Haumschild, PharmD, MS, MBA: Those are great comments. I like how you talked about the importance of overseeing the patient, the handoff. But also, what’s the most appropriate phase of care? Is it inpatient? What’s the right thing to discharge them on, what can we start in the outpatient [setting] for more long-term control?
Dr Januzzi, Dr Anderson teed you up there. From your perspective, how do you approach sequencing of therapies for your patients? Are you comfortable starting some patients on multiple drugs at once? Talk us through that a little. How do you decide what comes first?
Jim Januzzi, MD: Sure. Thank you for that. There are recent consensus documents from the American College of Cardiology, an expert consensus decision pathway document that discusses this very important topic: how to initiate and how to titrate. I encourage the viewers to look at that. It’s really useful. The simple truth is that every patient is unique, so there’s no cookbook for how to approach this. When I hear colleagues saying to start all 4 drugs at once, that isn’t reality. It isn’t feasible nor is it logical to start all 4 classes of drugs in heart failure at the same time, because if a person has an adverse effect, you don’t know which drug caused the problem. But there are ways to rapidly deploy these therapies so that a person can be on at least low doses of all 4 classes within a week or two.
Everyone is different in how they approach this, but I try not to overlap therapies that have similar adverse effects too closely. For example, I’ll initiate sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, together with a beta blocker. On the other hand, I won’t start sacubitril/valsartan and spironolactone or an SGLT2 inhibitor at the same time because they both might have renal adverse effects. I’ll remind the viewers that through their effects, SGLT2 inhibitors deliver sodium to the distal tubule, which leads to increased afferent arteriolar constriction. This is a pharmacologic effect that reduces GFR [glomerular filtration rate], but it isn’t acute kidney injury. When you start an SGLT2 inhibitor, it’s particularly worthwhile to remember that you may see worsening of the GFR, but that doesn’t mean there has been kidney injury. That’s why if you mix it together with a drug like a RAS [renin-angiotensin system] inhibitor, you might get confused as to which drug is causing dysfunction of the kidneys.
Generally speaking, if I’m going to do more than 1 drug at a time, I avoid the adverse effect profiles as much as possible. I typically lead with sacubitril/valsartan and a beta blocker, followed by a mineralocorticoid blocker. Then like a cherry on the sundae, I finish with an SGLT2 inhibitor. The key isn’t so much to get 1 drug up to whopping doses before we get another started. A bit of everything is far more important than a lot of 1 drug. Then you can focus on titration once you’ve initiated. The good news is that you’re nearly at target dose with MRAs out of the box immediately, and with SGLT2 inhibitors, it’s 1-and-done in terms of dose. It gets easier once you get through the earlier titration steps with beta blockers and sacubitril/valsartan.
Transcript edited for clarity.