The lack of approved treatments for heart failure with preserved ejection fraction has represented a significant unmet need for a condition that affects 50% of patients with heart failure, including large subgroups, such as older women.
At long last, the cardiology world on Friday expects to hear results it has sought for years—a prospective trial with clear results that a therapy offers benefits in heart failure across the full spectrum of ejection fraction, which will be good news for the 64 million people worldwide who have heart failure.
From Friday to Monday, the European Society of Cardiology (ESC) will hold its 2021 Congress in a virtual format for the second year, forgoing London due to COVID-19. The clinical trials scheduled to be presented will pick up where last year’s meeting left off, starting Friday with EMPEROR-Preserved, the long-awaited study of empagliflozin (Jardiance), which topline results show can reduced the risk of hospitalization and cardiovascular death (CV) for patients with heart failure with preserved ejection fraction (HFpEF).
Last year at the ESC Congress, results from EMPEROR-Reduced, involving patients with heart failure with reduced ejection fraction (HFrEF), showed that empagliflozin reduced the risk of CV death or hospitalization for heart failure by 25%, reduced renal events by 50%, and slowed the rate of renal decline.
Just this month, the FDA approved empagliflozin to treat HFrEF whether or not a patient has type 2 diabetes (T2D). The drug class of sodium glucose co-transporter 2 (SGLT2) inhibitors, which includes empagliflozin, was first developed to help patients reduce blood glucose through a unique mechanism of targeting a protein that allows patients to excrete glucose through urine.
But it was empagliflozin that first showed the potential of the class in heart failure in 2015, when the stunning results of the EMPA-REG OUTCOME trial showed a CV benefit from a diabetes drug for the first time, driven largely by the reduction in heart failure hospitalization.
Although there have been other therapies approved to treat HFrEF, until recently HFpEF has not had any approved therapies, and trials have not produced a clear-cut positive end point. Thus, the lack of HFpEF treatments represented a significant unmet need for a condition that affects 50% of patients with heart failure, including large subgroups, such as older women.
Earlier this year, Novartis won FDA approval for sacubitril/valsartan (Entresto) in certain patients with HFpEF, even though the therapy just missed achieving superiority in a critical phase 3 trial; instead, regulators evaluated a body of evidence across several studies and noted that subsets of patients had better outcomes.
HFpEF occurs when the left ventricle is unable to fill properly, causing an inadequate amount of blood to be pumped through the body, depriving the body and organs of adequate oxygen. It is a leading cause of hospitalization, and in the United States, Medicare has pressed health systems to develop ways to better care for these patients, who typically have other comorbidities and are often repeatedly readmitted at great cost to the health system. The risk of death rises each time a person is hospitalized with heart failure.
The release of topline results from drug sponsor Boehringer Ingelheim, which developed empagliflozin with Eli Lilly, suggested the benefit in HFpEF will be substantial.
“We look forward to presenting the EMPEROR-Preserved results at ESC 2021, which should offer a breakthrough in cardiovascular medicine and a new hope for people with HFpEF, which is an increasingly prevalent public health issue. HFpEF has long been the most challenging form of heart failure to treat,” Stefan Anker, MD, PhD, FESC, heart failure cardiologist at Charité Campus Virchow Clinic, Berlin, Germany, and EMPEROR-Preserved principal investigator, said in the statement.
Following Anker’s presentation of EMPEROR-Preserved, Milton Packer, MD, of Baylor College of Medicine, will present results from EMPEROR-Pooled on the effects of empagliflozin on adverse renal outcomes and end-stage kidney disease in patients with chronic heart failure across the heart failure spectrum, regardless of diabetes status.
More Clinical Trials, COVID-19
ESC Guidelines.Throughout the Congress, updated clinical guidelines will be presented in heart failure (Friday), valvular heart disease (Saturday), cardiac pacing (Sunday), and cardiovascular disease (CVD) prevention (Monday).
Finerenone. Saturday’s highlights include FIGARO-DKD, in which Bertram Pitt, MD, of the University of Michigan, will present results investigating the efficacy and safety of finerenone (Kerendia) compared with placebo to reduce CV and kidney outcomes in patients with chronic kidney disease (CKD) and T2D when added to standard of care. Gerasimos Filippatos, MD, of the University of Athens Medical School ,will present results from FIDELITY, involving finerenone in mild to severe CKD and T2D.
COVID-19. Multiple sessions will examine the effect of the pandemic on patients with CVD. Friday will feature both the symposium, “The Collateral Damage of COVID-19 on CVD,” and the abstract session chaired by Mikhail Kosiborod, MD, of St. Luke’s Mid-America Heart Institute, “Consequences of COVID-19 in Heart Failure: One Year On.”
REDUCE-IT vs STRENGTH. One of the more intriguing debates in the cardiology community in the past year involves results from the STRENGTH trial for the omega-3 carboxylic acid, which did not find the same benefits that were seen in the REDUCE-IT trial for the omega-3 icosapent ethyl. On Sunday, Børge Grønne Nordestgaard, MD, DMSc, of the University of Copenhagen, will present results of a paper with a study mimicking trial designs that tries to explain the divide.
STEP Study. Jun Cai, PhD, an actuarial scientist from the Chinese Academy of Medical Sciences of Beijing, will present results examining intensive vs standard blood pressure control among older patients with hypertension.
SGLT2 Inhibitors “Vastly Underutilized”
The Congress promises to further establish the role of SGLT2 inhibitors in treating heart failure, despite the resistance to prescribing by some physicians who still see them only as “diabetes drugs.”
In fact, Rudolf de Boer, MD, PhD, of University Medical Center Groningen, the Netherlands, told The American Journal of Managed Care® that SGLT2 inhibitors should be recognized for their multiple benefits. SGLT2 inhibitors are known to have modest antihypertensive effects and can help patients lose small amounts of weight. In the laboratory setting, they have been shown to normalize metabolic abnormalities common in heart and kidney disease.
“These are very elegant drugs,” he said. “They don't push particularly hard on one disease mechanism going wrong. But what they do is they normalize a number of parameters in a rather subtle manner. And that explains their clear efficacy on one side, but also their very favorable safety profile on the other end.”
Deepak L. Bhatt, MD, MPH, of Brigham & Women’s Hospital and Harvard Medical School, who will present new results during ESC 2021 from SCORED and SOLOIST involving the SGLT1/2 inhibitor sotagliflozin, said SGLT2 inhibitors are “a great class of medicines that are vastly underutilized.”
Bhatt said the latest results for sotagliflozin add weight to the argument that SGLT2 inhibitors should be given to patients with acute heart failure in the hospital before discharge. At this point, he said, there have been enough positive trials that practicing physicians should no longer need convincing about the drug class.
“If you're sitting on the sidelines, being a skeptic, well, then you're just one of those science deniers. The data for SGLT2 inhibitors are incredibly good,” he said. Patients must be well managed, and that’s where some clinical inertia is involved. But with evidence that the drugs work quickly, and the opportunity for hospitals and health systems to avoid 30-day readmissions, Bhatt said health systems and payers should work to improve access.
Last fall, the SCORED and SOLOIST trials had shown a signal for HFpEF, so Bhatt was not surprised by the news of the pending results for EMPEROR-Preserved. There’s a lot of excitement in HFpEF, he said, where the field has gone from having no real treatments other than symptom management to “now, we have evidence-based therapies for a common condition.”
“That’s a really big deal in cardiovascular medicine,” he said.