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New developments in heart failure research to improve outcomes in diabetes, cardiometabolic conditions
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PHILADELPHIA — New data from the several large cardiovascular outcomes trials, combined with an evolving understanding of the etiology of heart failure, are forcing clinicians and researchers to change the way they typically work with patients and each other, according to an organizer behind the first Heart in Diabetes conference.
Mikhail Kosiborod, MD, FACC, FAHA, professor of medicine at the University of Missouri-Kansas City and a conference co-chair, spoke with Endocrine Today about the importance of sharing research across specialties to improve CV outcomes in diabetes, the latest developments in diabetes-related heart failure research and the latest trials that could potentially change the landscape of heart failure treatment.
Why is it so important to promote a better understanding of heart failure in the setting of diabetes?
Kosiborod: Heart failure is emerging as one of the most important CV complications of type 2 diabetes and the cardiometabolic syndrome. A lot of heart failure has effects at earlier stages of the cardiometabolic syndrome, including prediabetes, and people with pre-existing kidney diseases as well. It has been underappreciated for a long time, but it is the most common CV complication of patients with type 2 diabetes and the complication with the highest morbidity. A better understanding of the ways to both prevent and treat heart failure is critical to improving survival, as well as quality of life, in this patient population.
The Heart in Diabetes conference will focus on the intersection of cardiology, endocrinology and nephrology, among other subspecialties. Why is that intersection important when discussing heart failure in diabetes?
Kosiborod: The [combined] field is really becoming its own. You could call them “cardio-diabetologists” or “endocrine-cardiologists” or “diabetacardiologists” — people are joining this combined field from various specialties. There are also primary care physicians and nephrologists entering the field. It is incredibly important because, of course, what patients with diabetes primarily die from is CV complications, but also renal complications. Between those two causes of morbidity and mortality in this patient population, you are accounting for most of the compilations. We now have several classes of treatments shown to be effective to markedly improve outcomes in this patient population, through the effects on the CV system as well as the kidneys.
What has changed recently in heart failure research related to diabetes ?
Kosiborod: The epidemiology of heart failure is evolving. We used to think of heart failure as a disease of the myocardium; specifically, a weakening of the myocardium, or heart failure with reduced ejection fraction. But if you look at the epidemiology, it is rapidly evolving. A lot of people admitted to the hospital actually have a condition known as heart failure with preserved ejection fraction. Unlike heart failure with reduced ejection fraction, where the myocardium is the main source of trouble, heart failure with preserved ejection fraction is a cardiac manifestation of this cardiometabolic syndrome. It is reacting to all the things that occur in patients with pronounced cardiometabolic syndrome: obesity, a pro-inflammatory state, hypertension, renal-sodium retention, hyperfiltration injury and progression of chronic kidney disease, sleep apnea, atrial fibrillation. This phenotype of heart failure is a cardiac manifestation of that systemic disease.
What are some of the promising new therapies to treat both types of heart failure in the setting of diabetes?
Kosiborod: There are several emerging treatments that are promising. One, clearly, is SGLT2 inhibitors. We now have data from two clinical trials — EMPA-REG Outcome and CANVAS — indicating that both empagliflozin (Jardiance, Boehringer Ingelheim and Eli Lilly) and canagliflozin (Invokana, Janssen) reduce hospitalization for heart failure with a really impressive effect size. In both trials, you see both a clinically meaningful and statistically significant reduction in heart failure hospitalizations, with both compounds. Most patients in those trials did not have heart failure — [the effect] appears to be, primarily, heart failure prevention, which is very important. These agents may also be effective for treatment of people with established heart failure. The CVD-REAL study, a large, real-world evidence study, also indicates that this prevention of heart failure or a heart failure effect, in general, appears to be a class effect. Because these agents appear to be effective in preventing hospitalization for heart failure, they may be effective in treating heart failure as well, regardless of diabetes status.
What resea rch in the pipeline a re you most looking forward to seeing?
There are lots of exciting things. The DECLARE-TIMI 58 trial, which is the third and largest trial of SGLT2 inhibitors in patients with diabetes, is going to include a large population of patients both with and without established CVD. This study will promote a better understanding of whether these agents are primarily effective in patients with diabetes and established disease, or whether they provide similar cardioprotection and nephroprotection in people who have not yet had a cardiac event. There will also be more data to come from CVD REAL, which already made a substantial impact and will continue to do so. And there are ongoing trials in patients with heart failure, including the EMPA-HF program that includes two trials, one with reduced ejection fraction and one with preserved ejection fraction, and the DAPA-HF trial, dapagliflozin (Farxiga, AstraZeneca) in patients with heart failure with reduced ejection fraction. Both programs include people with and without diabetes. There are also several investigator-initiated trials, including DEFINE-HF and PRESERVED-HF, both ongoing, that look at dapagliflozin, specifically in people with both reduced and preserved ejection fraction heart failure, and EMBRACE-HF, looking at empagliflozin in people with heart failure and diabetes. There is a lot going on in the field, which will give us a wealth of data in the coming years, both in patients with and without diabetes. – by Regina Schaffer
Disclosure: Kosiborod is a co-chair of the Heart in Diabetes conference. He reports various financial ties with Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Eisai, Eli Lilly and Company, GlaxoSmithKline, Glytec Systems, Merck & Co., Novo Nordisk, Sanofi, Takeda Pharmaceutical Company and ZS Pharma.