Q&A – Heart Failure and SGLT2 Inhibitors
Tune in to hear Andrew Freeman, MD discuss the impact of SGLT2 inhibitors for the treatment of heart failure.
Transcript
Victoria Bradley: Hi everyone, and welcome to today's Q&A session on heart failure and SGLT2 inhibitors. My name is Victoria, and I will be your moderator for today's discussion. I am pleased to introduce our guest, Dr. Andrew Freeman. Dr. Freeman is a board-certified cardiologist who has been practicing in the field for over 20 years. Dr. Freeman, thank you so much for being here with us today.
Dr. Andrew Freeman: Oh, it's my pleasure.
Victoria Bradley: My first question for you is, what is the mechanism of action of SGLT2 inhibitors in the treatment of heart failure?
Dr. Andrew Freeman: Sure. For those who may not be familiar, SGLT2 inhibitors were originally released for diabetic management. It turns out they also address the entire spectrum of cardiometabolic kidney diseases, including heart failure. SGLT2 inhibitors have now become a pillar in the treatment of heart failure. They block SGLT2 proteins in the kidneys, causing the excretion of sugar and salt. This results in reduced plasma volume, decreased blood pressure, and alleviates the workload on the heart. However, there's a risk of infection due to the excretion of sugar, so it's important to ensure excellent pelvic hygiene, especially for older patients. The mechanism induces osmotic diuresis and natriuresis, reducing plasma volume and blood pressure, which lowers the pressure the heart pumps against. These changes improve heart efficiency. Additionally, these drugs have been associated with reductions in serum uric acid levels, which have various cardiovascular benefits. Overall, it's an amazing class of drugs that works through the excretion of urinary glucose and sodium.
Victoria Bradley: Great. Thank you. Can you tell us more about some major clinical trials that have demonstrated the efficacy of SGLT2 inhibitors in heart failure?
Dr. Andrew Freeman: Sure. I'll summarize a few key trials:
- DAPA-HF: This trial looked at dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status. It was a randomized, double-blinded, placebo-controlled trial with 4,744 patients. Participants received either DAPA 10 mg or placebo in addition to standard therapy. There was a significant risk reduction of around 26% for those on DAPA.
- EMPEROR-Reduced: This trial studied empagliflozin in HFrEF patients. It included 3,730 patients and showed a 25% relative risk reduction for those on EMPA.
- EMPEROR-Preserved: This trial focused on empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). It included nearly 6,000 patients and showed a 21% relative risk reduction.
- SOLOIST-WHF: This trial looked at sotagliflozin in type 2 diabetes patients recently hospitalized for worsening heart failure. It involved 1,222 patients and showed a significant reduction in primary endpoints compared to placebo.
- DEFINE-HF: This trial studied dapagliflozin on heart failure symptoms and biomarkers in HFrEF patients. It included 260 patients and showed that a higher proportion of patients in the DAPA group had clinically meaningful improvements in heart failure symptoms or NT-proBNP levels compared to placebo.
Overall, these trials demonstrate significant reductions in heart failure symptoms, biomarkers, and better outcomes, making SGLT2 inhibitors guideline-directed.
Victoria Bradley: Absolutely. Thank you for taking us through those. Can you talk about which patient populations should be considered for SGLT2 inhibitors in heart failure management?
Dr. Andrew Freeman: In general, most heart failure patients should be on an SGLT2 inhibitor unless there's a contraindication like recurrent urinary tract infections. They are effective for both HFrEF and HFpEF. It's lovely to keep people out of the hospital, feeling better, and more functional. The data supports that SGLT2 inhibitors work great for all forms of heart failure.
Victoria Bradley: How do SGLT2 inhibitors compare to other guideline-directed therapies for heart failure?
Dr. Andrew Freeman: They are complementary, not replacing anything. People should be on renin-angiotensin system inhibitors like ACEs, ARBs, or ideally ARNIs (sacubitril/valsartan). These agents reduce mortality and morbidity by interfering in neurohormonal pathways. Beta-blockers decrease sympathetic nervous system activity, improve survival, and reduce hospitalization. Mineralocorticoid antagonists (MRAs) are very effective in improving outcomes, despite requiring additional monitoring. SGLT2 inhibitors offer unique benefits like diuretic effects without significant electrolyte disturbances and positive effects on kidney function. Many heart failure patients have cardiometabolic kidney disease, diabetes, coronary disease, and sleep apnea. Treating these patients with SGLT2 inhibitors has overall benefits. These drugs initially came out for diabetes but affect everything, including heart failure.
Victoria Bradley: How do SGLT2 inhibitors provide cardiovascular benefits in heart failure beyond glycemic control, and what are the key differences in their effects between diabetic and non-diabetic patients?
Dr. Andrew Freeman: They provide glycemic control for diabetic patients but also have other cardiovascular benefits. They induce osmotic diuresis and natriuresis, lowering blood pressure, reducing plasma volume, and decreasing cardiac workload. They promote a shift towards ketone body utilization, enhancing myocardial energy efficiency. There appear to be anti-inflammatory and anti-fibrotic effects, reducing cardiac inflammation and fibrosis, improving cardiac structure and muscle function. These benefits are observed in both diabetic and non-diabetic patients, making SGLT2 inhibitors crucial in heart failure management regardless of glycemic status. Cardiologists need to embrace that these are not just diabetic drugs. Lipids and cholesterol were once the domain of endocrinology but are now squarely in cardiology. This experience can translate into better heart failure outcomes.
Victoria Bradley: Absolutely. Thank you so much for sharing your insights today. I certainly learned a lot, and I hope our audience had a good refresher on these topics. Thank you for your time today, and we hope to see you again soon.
Dr. Andrew Freeman: My pleasure. Thanks for having me.
Transcript Edited for Clarity
