Expert: SGLT2 Inhibitors Show Benefit in Cardiovascular Disease Regardless of Diabetes

In an interview with Pharmacy Times, Anastasia Armbruster, PharmD, FACC, BCCP, discussed her presentation at the American College of Cardiology 2023 Scientific Session. Armbruster’s session focused on SGLT2 inhibitor use in patients with cardiovascular disease and considerations for patients with or without diabetes.

Q: How and when are SGLT2 inhibitors indicated for patients with cardiovascular disease?

Anastasia Armbruster, PharmD, FACC, BCCP: Yeah, great question. And this is certainly something that's been evolving very rapidly over the past few years. So, for patients with diabetes, of course, this is a diabetes treatment, and it has been for several years. But now with added indications for those with atherosclerotic cardiovascular disease (ASCVD) or a high risk of ASCVD; heart failure regardless of ejection fraction, which is a very new addition; and then also those with chronic kidney disease (CKD). So, there's been some really exciting data in that space. And really, the answer is for those patients without diabetes [there are] similar indications to lower their risk of events, as well as heart failure outcomes, and slow the progression of CKD. And interestingly, the ADA guidelines, the most recent addition, recommend these agents much earlier in the course of treatment for diabetes based on all of these benefits that have been documented over the past few years.

Q: Can you review some of the key data supporting their use?

Anastasia Armbruster, PharmD, FACC, BCCP: Yeah, so there were some early trials looking at the ASCVD portion, so cardiovascular risk, and going back further, all of this really came about because of those medications treating diabetes that had poor outcomes in this patient population. So really, this group of medications were just doing their due diligence to make sure that these were not harmful for patients with cardiovascular disease. And there were some early signals like reducing heart failure hospitalizations, even though there were a low percentage of patients with heart failure enrolled in those trials, like DECLARE. So then came DAPA-HF and EMPEROR-Reduced, which both demonstrated a reduction in a composite outcome of [cardiovascular] death and heart failure hospitalizations, for patients with and without diabetes. And so that was really the turning point that maybe these medications aren't just for diabetes anymore, and they're really reducing heart outcomes in patients with heart failure. Really, between both trials, the number needed to treat was around 20, with 12 months of treatment, which is, you know, a great outcome, especially in patients with heart failure, who can be frequently hospitalized. And this is this is now, with the most recent heart failure guidelines, considered one of the 4 pillars of guideline-directed medical therapy for patients with heart failure with reduced ejection fraction.

A little bit about the CKD data. There was demonstrated a sustained decline in GFR of at least 50% reduction in stage progression to end-stage kidney disease or death from renal or cardiovascular causes. So again, showing reduction in that composite endpoint. It’s really an exciting development for in the CKD space as well. If we think about other medications that are beneficial in that population, it's been a number of years since we've seen something to reduce those endpoints for those patients.

Q: What considerations are there for patients before starting treatment with SGLT2 inhibitors?

Anastasia Armbruster, PharmD, FACC, BCCP: Sure, I think that overall, this drug class is very well tolerated. In my practice, I see primarily heart failure patients with reduced ejection fraction, some preserved as well. And overall, it's a very well-tolerated drug class. A couple of things you do need to check—renal function. So right now, as it stands, each drug has EGFR cut-offs of 20 and 25 to consider. And then [they are] currently not indicated in patients on hemodialysis. So, renal function is a consideration. Luckily, those aren't huge limitations, a lot of our patients are still able to receive the medication. There is a small risk for diabetic ketoacidosis, which gets a lot of traction with physicians. I think they worry about causing such a serious adverse event, which is certainly appropriate. So really just looking for patients, maybe, who are uncontrolled, so their A1c is like greater than 10 and their insulin is being titrated and, you know, those many patients where we kind of hold or wait until things have improved. And there's certainly a risk of genital mycotic infections. And so, you know, it really comes down to a hygiene conversation. But the risk is certainly increased with this drug class.

Q: How do these considerations differ for patients with and without diabetes?

Anastasia Armbruster, PharmD, FACC, BCCP: I wouldn't go as far to say that patients without diabetes have no adverse effects, but a lot of the adverse effects I just mentioned really are with those patients with diabetes. There are hardly, if any, case reports of euglycemic DKA in patients without diabetes, of course, just based on the pathophysiology of that and development of that adverse effect. And really, a lot of the considerations that we have, like looking at A1c, the dose of insulin, all would just, of course, be for patients with diabetes. So, in those without [diabetes], there's really not as many considerations to kind of prevent us from treatment. Of course, renal function still matters. And we still talk to patients about mycotic infections, but incidence is much higher in those patients with diabetes. Sometimes patients are concerned, “I don't have diabetes, and you're putting me on a medication for diabetes.” There were little to no reports of hypoglycemia in patients without diabetes in the trials, and really based on the mechanism of action, it's not something we are concerned about, but it's good to talk to patients about and continue to educate providers that, yes, it can lower blood glucose, but less so in patients without diabetes.

Q: How are pharmacists involved in these treatments and considerations?

Anastasia Armbruster, PharmD, FACC, BCCP: At first, I work primarily with cardiologists, and I think they were wanting to stay in their lane. Like, this is a diabetes medicine, should I really be initiating it? There's a lot of other things I'm not used to considering. And so, I think pharmacists had a crucial role in making sure providers were aware of the data supporting them, for maybe adverse effects that they're not used to monitoring for or even treating. Certainly, cardiologists weren't excited about treating genital mycotic infections, but we can get through that together, right? That's a great role for pharmacists to play in the treatment and care of patients. So, there's a lot of opportunity for just education. And for patients, as well, as I mentioned, you're starting on a diabetes medicine, but I don't have diabetes, why is that? And really just outlining the strong clinical benefit to the patient and kind of working through formulary issues. All the usual things that pharmacists are a part of. But really getting over that barrier of “This medicine is for diabetes” has been a big world for pharmacists.

Q: How can pharmacists educate patients about these considerations?

Anastasia Armbruster, PharmD, FACC, BCCP: Sure. I think that in addition to those patients without diabetes, kind of comforting them that they're not going to get low blood sugar, you know, there are a few ways we can reduce the risk of euglycemic DKA, such as holding the medication 3 days before procedure or surgery, I think that's an important education point. A lot of times, if a patient's going for a surgery, you know, providers may be focused on holding blood thinners or baby aspirin, things like that. But it's important for the patient to be involved and be knowledgeable that if you're going to have a procedure or surgery, it's important to hold this medication to reduce that risk. Diabetic patients are familiar with the concept of sick days, but kind of applying those concepts. And again, this is really to prevent euglycemic DKA. And for a lot of patients, it's going to be, you know, a precaution that may not be completely necessary, but it certainly reduces the risk. So that's something we talked to them about. Again, personal hygiene, recognizing the signs and symptoms of a genital mycotic infection so it can be treated quickly and efficiently. These medications can cause volume depletion so again, just things with other heart failure medicines we talk to patients about, anyway. Monitoring your blood pressure, do you feel dizzy when you stand up? Just kind of reinforcing all of those things. And then, not that pharmacists love this conversation, but really talking about costs. I'm always open with patients, either medication we choose, Farxiga or Jardiance, they're both still brand name copays. So, we try to look at the patient's formulary, give them the best chance they can to have an affordable option. But I think it's really important to outline those clinical benefits and share decision making as these medications can be expensive for some patients.

Q: Is there anything you want to add?

Anastasia Armbruster, PharmD, FACC, BCCP: No, I think we covered a lot of the important points. I think overall use is still fairly low. Even though this is now considered a pillar of heart failure therapy based on guideline recommendations, really for multiple disease states now, I focus mostly on heart failure. But the CKD data is quite compelling, as well. And certainly, cost can be prohibitive for many patients but also many patients could benefit from the therapy. So, to me it's kind of a “just do it” situation. And so just kind of advocating for our patients to ensure they're receiving the most up to date guideline directed therapy.