Role of SGLT2 Inhibitor Therapy for HF Treatment

James Januzzi, MD: In the ACC [American College of Cardiology] Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment document, we take the experience from clinical trials in diabetes and heart failure, as well as our own experiences regarding for whom we would prescribe these drugs, in whom we might avoid them, and some important tips about what to expect when you use them. Javed, can you offer some clinical pearls about what to expect when you start an SGLT2 [sodium-glucose cotransporter-2] inhibitor in patients with heart failure?

Javed Butler, MD, MPH, MBA: Yes. There are lessons learned about population, but you have to be very careful not to apply it to every single patient sitting in front of you. We are clinicians, and we should use our best judgment. If you look at the overall population data in the diabetes trial, there was a reduction in systolic blood pressure by about 4 or 5 mm Hg with the SGLT2 inhibitors. That is great because this is not an antihypertensive drug. These patients tend to be hypertensive, so that’s a benefit. Patients with reduced ejection fraction actually tend to have lower blood pressure. We have seen that with other vasoactive agents, as well. They don’t lower blood pressure as much, because by improving hemodynamic vasodilation, you improve cardiac efficiency.

We’re seeing with the SGLT2 inhibitors that the decrease in blood pressure that was seen in diabetes was not replicated. There was no statistically significant difference in blood pressure. Having said that, we shouldn’t be too careless with the person sitting in front of us who’s already orthostatic or may be older. We should take some caution. You already mentioned cutting down the dose of diuretics. Interestingly enough, in the overall population, you do not have to change the diuretic a lot, but I would still use caution when I’m seeing a person in front of me.

James Januzzi, MD: Yes, that’s an important nuance in the differences between SGLT2 inhibitors and sacubitril/valsartan. In our noncongested patients, we routinely will reduce loop diuretics in our patients for whom we initiate sacubitril/valsartan. With SGLT2 inhibitors, we tell them, “This may increase your diuresis. Weigh yourself, as you always should. Let us know if you‘re becoming dehydrated or losing too much weight.” You will see a rather exaggerated diuretic effect in about 1 in 10 patients. I have no idea how to explain that other than to say that SGLT2 inhibitors probably have multiple pathways that they‘re affecting, and in some patients, it’s the diuretic effect that is most obvious early on.

The other thing we warn patients about, and this is in the document as well, is that through their mechanism of action, sodium-glucose cotransporter-2 drugs increase the amount of glucose in the urine, which is particularly an issue for patients with diabetes. In a patient who doesn’t have diabetes, this is not an issue. But in those with higher circulating blood glucose levels, above 160 to 180 mg/dL is when you start seeing glycosuria developing. There is a risk for an increased rate of pelvic yeast infections. That’s typically vaginal yeast infections in women. In men, it is largely related to the lack of circumcision. It may be the one time that a heart failure cardiologist may be asking about circumcision, but it’s an important issue, because self-care and hygiene can help reduce the risk for these complications. A lot was made early on about the risks related to SGLT2 inhibitors in patients with peripheral arterial disease and the risk for amputation. We have discounted that quite heavily now. In fact, the FDA black box warning about risk for amputation on one of the SGLT2 inhibitors has been removed. These are actually a well-tolerated group of medications that should be added early as part of the fundamental therapeutic choice for our patients with heart failure with reduced ejection fraction.

Transcript Edited for Clarity