Podcast 2: Heart Failure Management for Non-Specialists: Focus On SGLT2 Inhibitors

00:00:00: You are listening to an ADIS journal podcast.

00:00:06: My name is Nehaar Desai, I'm an associate professor of medicine and vice chief for the section of cardiovascular medicine at The Yale University School Of Medicine in New Haven Connecticut.

00:00:15: Welcome to episode two of this podcast series exploring heart failure And Heart Failure Management For endocrinologists primary care physicians and non-cardiologist clinicians.

00:00:27: In Episode one we gave a pragmatic overview of heart failure focusing on early detection, screening and diagnosis.

00:00:35: Today I'm joined again by Dr.

00:00:37: Enzuki and Dr.

00:00:39: Wright to discuss the treatment options for patients following diagnosis or in patients at risk of heart failure.

00:00:46: Good to talk to you again!

00:00:48: My name is Eugene Wright And i am a consulting associate In The Department Of Medicine At Duke University at the South Piedmont Area Health Education Center here in Charlotte, North Carolina.

00:01:03: And I'm Sylvia Onzuki and I am a clinical chief of this section of endocrinology also at the Yale School of Medicine and medical director of The Yale Diabetes Center at Yale New Haven Hospital.

00:01:13: Thank you both for talking with me again today.

00:01:16: We spoke about screaming an early detection of heart failure in patients with type two diabetes In our first episode as a primary care physician, Eugene.

00:01:28: What's typically done after you've identified the patient at risk of heart failure or once they received a heart-failure diagnosis?

00:01:36: Primary care physicians regularly see patients with type II diabetes at risk for heart failure which is we mentioned in previous episode actually stage A heart failure.

00:01:48: Patients seen in primary clinic are often living and managing comorbidities such high pretension obesity, chronic kidney disease and diabetes that are known to worsen heart failure prognosis.

00:02:02: In fact over eighty-five percent of patients with heart failure have two or more additional chronic conditions.

00:02:09: therefore managing comorbidities is a key element for heart failure treatment and preventing progression of heart failure.

00:02:17: this often includes lifestyle modifications such as getting regular exercise eating healthy diet and smoking cessation to manage blood pressure, control weight and improve cardiovascular health.

00:02:30: In addition there's a direct relationship between dietary sodium intake in blood pressure so reducing salt intake is common self-care behavior that is recommended for patients who have high blood pressure and edema.

00:02:45: Working with patients to improve sleep quality if something clinicians can also consider as sleep deprivation has been associated coronary heart disease and diabetes.

00:02:56: Conditions such as obstructive sleep apnea lead to poor sleep quality, but sleep quality is of prognostic importance for all patients with heart

00:03:06: failure.".

00:03:06: Yeah thanks Eugene.

00:03:07: I very much agree.

00:03:08: i think lifestyle modifications can be vital to preventing the progression of heart failure and are valuable to include in the treatment regimen for patients across the stages.

00:03:18: In your experience, Eugene I'm curious.

00:03:20: what medications are typically prescribed for patients with early stage heart failure in the primary care clinic to manage their comorbidities?

00:03:29: Pharmacological interventions.

00:03:31: In addition to lifestyle modifications is also important to manage comorbidity's and patient at risk of heart failure or with early-stage heart failure.

00:03:40: beta blockers and Winnon angiotensin system modifying drugs are commonly used to reach blood pressure targets.

00:03:51: In addition, hyperlipidemia and high cholesterol require treatment with statins for example To reduce the risk of heart failure progression And atherosclerotic cardiovascular disease.

00:04:03: Because chronic kidney diseases in heart failure Are closely linked pathophysiologically Pharmacological management of renal dysfunction is important And while, as we've already discussed conditions such is obesity may initially be managed with changes in lifestyle, pharmacological intervention might also considered some cases.

00:04:27: In patients with diabetes glycemic control is essential to reduce the risk of heart failure and improve heart failure prognosis.

00:04:35: for every one percent increase in A-one C, risk hospitalization for heart failure increases by eight to thirty two per cent.

00:04:44: While metformin is often the preferred initial glucose lowering medication for people with type two diabetes, combination therapy is often required to maintain glycemic control manage risk and treat comorbidities.

00:04:58: Thanks Eugene.

00:04:59: I think it's also worth mentioning that patients with type-two diabetes who have controlled plasma glucose are still at increased risk of cardiovascular events so management is important in this population.

00:05:15: As a substantial proportion of patients with type II diabetes will also have cardiovascular disease or other risk factors for heart failure, SGLT-II inhibitors such as epigliflozin and dapagliflosin should be considered.

00:05:30: This reflected current guidelines which suggest treatment of cardiovascular outcomes in people with type II diabetes.

00:05:46: These SGLT-II inhibitors represent an intersection between cardiologists, endocrinologists and primary care physicians.

00:05:54: Silvio you were involved in the clinical trials for some of these SGL T-II inhibitors which first showed cardiovascular benefits in patients with Type II Diabetes.

00:06:04: can you talk us through the impact that these medications can have?

00:06:08: For patients with heart failure those with and without diabetes?

00:06:12: Well, Nihara as you pointed out the SGLT-II inhibitors were first developed actually as glucose lowering medications for people with type II diabetes.

00:06:21: Now following some controversies about the cardiovascular safety of certain glucose lowering agents in early two thousands The US Food and Drug Administration began to mandate that all new diabetes medications should at the very least demonstrate no increase major adverse cardiovascular events.

00:06:43: So, a series of large CV outcome trials or CVOTs were undertaken for newer drugs for type II diabetes.

00:06:53: Amongst these trials those focused on the SGLT-II inhibitors showed somewhat surprising cardioprotective effects in patients who are at high risk including a reduction in the risk of major adverse cardiovascular events or MACE, and also the really important outcome of hospitalization for heart failure.

00:07:20: The next question was might these medications also be effective for patients with heart failure who did not have diabetes?

00:07:29: Both empirical flowsin' and dapical flowzin' demonstrated reduced risks of cardiovascular death and hospitalization for heart failure in patients with heart failure, and reduced ejection fraction or HEF-REF including those without diabetes.

00:07:45: Very similar risk reduction between those within without diabetes in these trials.

00:07:51: Similar results were then found in Heart Failure With Preserved Ejection Fraction or HEV-PEF.

00:07:58: again both with embigaflozin and dapagoflozin And also regardless of the diabetes status.

00:08:06: Mechanical flows in has also been shown to reduce heart failure events and patients with diabetes.

00:08:12: And there was some initial promise in patients with heart failure who did not have diabetes, however it is not approved for heart failure specifically because large-scale heart failure trials had not been conducted at that

00:08:25: age.".

00:08:26: The same applies More recently, empirical flows has been investigated in the acute heart failure setting.

00:08:37: In patients hospitalized for heart failure and demonstrated reduced mortality in these patients also regardless of diabetes status and interestingly Also regardless of ejection fraction.

00:08:51: So within a very short number of years The SGLT-II inhibitors have now become key part of heart failure treatment and are included in all major guidelines.

00:09:04: So Sylvio, what advice would you give primary care physicians when seeing their patients who were receiving SGLT-II inhibitors?

00:09:13: In terms of precautions and managing adverse events?

00:09:17: Well Eugene patient education is always going to go a long way in managing any adverse event from any medication.

00:09:25: The common adverse events that we see with the SGLT-II inhibitors include genitourinary infections, predominantly gentle yeast infections.

00:09:35: Also volume depletion leading to dehydration and rarely hypoglycemia only when used.

00:09:43: other diabetes medications themselves lower blood glucose into the hypoglycemia range.

00:09:50: this would include sulfonolureas as well insulin.

00:09:54: So patients who are prescribed SGLT-II inhibitors should be advised to keep their hydration levels up, to avoid volume depletion and maintain good gentle hygiene.

00:10:04: To minimize the risk of these infections other meds that our glucose lowering as mentioned like insulin and the cell funderias but also diuretics That can aggravate volume depletion may need to be dose adjusted or discontinued to avoid hypoglycemia and or hypotension respectively.

00:10:28: In the rare event of diabetic ketoacidosis, a rare adverse event in type II diabetes, the SGLT-II inhibitors should be

00:10:38: discontinued.".

00:10:39: Thanks so much Silvio.

00:10:40: I think you know something of interest that you mentioned was.

00:10:44: the use of hospitalizations as an endpoint to hospital admissions is not only terrible for patients with heart failure, but also represents an increased risk of subsequent hospital admissions and death.

00:11:02: With mortality risks increasing progressively...with each hospital admission.

00:11:08: Hospitalizations are the largest component in direct medical costs for heart failure—with estimates ranging from forty-nine percent to seventy three percent total cost…and approximately eighty percent Yep,

00:11:24: as I mentioned before in clinical trials with patients with heart failure both dapagaflowsin and empagaflozin reduced the risk of hospitalization for heart failure.

00:11:33: With empagoflozin also reducing the risk.

00:11:35: all cause hospitalizations.

00:11:38: The majority of cardiovascular outcome trials report reductions in hospitalization For heart failure And all-cause hospitalizations As outcomes mainly In secondary analyses.

00:11:50: A recent meta analysis Of five Pivotal SGLT-II inhibitor trials estimated a twenty nine percent reduction in heart failure hospitalizations and an eleven percent reduction.

00:12:03: In all cause hospitalizations, it's also worth mentioning that many patients in the original diabetes CV outcome trials did not have hard failure at baseline.

00:12:14: they were recruited as you recall due to their high risk for atherosclerotic events.

00:12:20: so A large driver of the reduction of hospitalizations seem to be through the prevention of new heart failure.

00:12:28: That's a really interesting point, Silvio.

00:12:30: I think another class of drugs that have shown promising results in The Reduction Of Heart Failure.

00:12:37: Hospitalizations Are Of Course The Mineral Corticoid Receptor Antagonists So We Know.

00:12:41: Meta-Analyses Of Rals Emphasis HF Topcat And Fine Arts Hf Collectively Investigating Spinal Lactone a plurinone and most recently, phenyrinone showed significant reductions in hospitalization for heart failure.

00:12:57: For patients with heart failure across the left ventricular ejection fraction spectrum.

00:13:02: The same pattern was then observed for total heart failure hospitalizations With or without cardiovascular death.

00:13:10: Slowing and preventing progression of heart failure is key as primary care physicians.

00:13:16: an endocrinologist that typical patient with diabetes did we see is someone with early-stage heart failure and early stage chronic kidney disease.

00:13:25: Who was at risk for developing symptomatic heart failure?

00:13:28: So understanding that diabetes, with heart failure should be treated early and aggressively With the goal being to prevent hospitalization And worsening of heart failure symptoms and not delaying That treatment is essential.

00:13:43: Yeah absolutely Eugene.

00:13:44: I think that's such an important point.

00:13:46: Collaboration between cardiologists, primary care physicians endocrinologist and other healthcare professionals is key to ensuring that patients receive guideline-directed medical therapy.

00:13:57: And support with lifestyle changes ultimately improving outcomes for patients with diabetes in heart failure.

00:14:04: I should also say there's this additional point of discussion around the use of SGLT to inhibitors in combination and in patients without diabetes that we don't have time to discuss today, but I would encourage listeners to explore this further in the scientific literature.

00:14:24: Thank you again Eugene and Silvio for joining me on this discussion of The Treatment Landscape For Patients With Diabetes And Hard Failure.

00:14:31: Please also join us next time for episode three of this podcast series where will talk about coordinated collaborative care.

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