SGLT-2 Inhibitors: The New Kid on the CHF Block

We have spent a couple blogs discussing heart failure (CHF)—what it is and how we treat it. As time goes on, our armamentarium has expanded. When I started practicing cardiology over 25 years ago, ACE (angiotensin converting enzyme) inhibitors had recently been found to save lives and prevent progression of CHF in patients with systolic heart failure. They became the first “must use” medication for this condition. At that time, beta blockers—particularly carvedilol—were just being established as the second category of medication all patients should be taking for systolic heart failure. And a few years later, mineralocorticoid receptor antagonists became part of a “triple therapy” regimen.

The category of ACE inhibitors was broadened around that time to include a “cousin”: ARBs (angiotensin receptor blockers). It would be 15-20 years before another medication became part of this triple therapy: Entresto, which is a combination of valsartan and sacubitril.  Entresto, though, includes an ARB (valsartan), so it is used instead of an ACE inhibitor or ARB, not on top of it.

Recently, though, a completely new category of medication—so-called SGLT2 (sodium glucose co-transporter 2) inhibitors have been discovered to reduce CHF hospitalizations and decrease mortality. The story behind this realization is quite interesting. SGLT2 inhibitors were developed to treat diabetes.  Because some of the previous diabetes medications had been shown to worsen cardiovascular outcomes—a critical issue for diabetics, who have a strong tendency to develop cardiovascular disease—the FDA decreed several years ago that all new diabetes medications had to undergo testing to make sure that they were safe for patients with heart disease.

When SGLT2 inhibitors were looked at (this category includes Jardiance®, Farxiga®, and Invokana®), they turned out not only to be safe, but to actually reduce hospitalizations for CHF and diminish cardiovascular mortality. Then further testing revealed that the drugs Jardiance® and Farxiga® had the same benefits in patients who don’t even have diabetes!

The way that SGLT2 inhibitors work in diabetes is by decreasing the kidney’s reabsorption of glucose (sugar). This occurs alongside a decreased reabsorption of sodium, which is clearly of benefit to patients with CHF, where there is a marked tendency to hold on to sodium and—along with that—fluid, which creates lung congestion and swelling.

But the benefits of SGLT2 inhibitors appear to go beyond the effects of removing sodium from the body. Researchers have several theories as to what other benefits these drugs provide that reduce CHF and death. These include lowering blood pressure, decreasing aortic stiffness, improving the efficiency of energy utilization by the heart, and decreasing sympathetic (think adrenaline) drive, amongst other things.

We have now updated our algorithm for CHF management, where SGLT2 inhibitors are now the fourth leg of therapy for systolic heart failure. So, if your cardiologist starts you on one of these medications, don’t be surprised. She’s not trying to become your diabetes doctor—she’s just finding a new way to keep your heart healthy!

Greg Koshkarian, MD, FACC


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Gregory Koshkarian, MD, FACC