Dapagliflozin Meets Quality-of-Life Marks, Efficacy Among Seniors, Data Show

Dapagliflozin, the type 2 diabetes (T2D) therapy that recently received an indication in heart failure (HF), meets all 3 criteria for managing the condition outlined in an FDA draft guidance for industry, according to a commentator reviewing data being presented Sunday on the therapy.

Carolyn S.P. Lam, MBBS, PhD, FRCP, FAMS, FESC, FACC, of the National Heart Centre in Singapore and professor, Duke-National University in Singapore, spoke at a press conference ahead of her appearance at a late-breaking session at the 2019 American Heart Association Scientific Sessions in Philadelphia, Pennsylvania, where she was set to comment on 2 additional analyses from DAPA-HF, a trial released in September that found the sodium glucose cotransporter 2 (SGLT2) inhibitor works equally well in patients with and without diabetes in reducing cardiovascular (CV) death and HF events in patients with HF with reduced ejection fraction (HFrEF).

“Dapagliflozin now fulfills all 3 goals of heart failure management,” Lam said. “Patients die less, are hospitalized less, and feel better—regardless of age or diabetes status.”

If these data are confirmed in other ongoing trials, she said, “This really suggests that dapagliflozin may be the next foundational pillar of HFrEF treatment.”

Dapagliflozin, sold as Farxiga by AstraZeneca, received an indication from FDA in October to reduce the risk of hospitalization for HF for patients with type 2 diabetes and established CV disease or multiple CV risk factors.

On Saturday, an analysis from DAPA-HF showed that patients who had received the best medical therapy nonetheless saw substantial benefits from the addition of dapagliflozin, which reduced the risk of CV death and worsening of HF by 27%. This morning, Mikhail Kosiborod, MD, professor of medicine, St. Luke’s Mid-America Heart Institute/University of Missouri at Kansas City, presented data showing that more patients taking dapagliflozin for HF had improved quality of life compared with placebo, and this was true regardless of how serious their symptoms were at baseline.¹

Kosiborod explained that at 4 months and at 8 months, patients answered 23 items from the Kansas City Cardiomyopathy Questionnaire (KCCQ), which he called the “gold standard” for gathering patient-reported outcomes (PROs) across 4 domains: frequency and severity of symptoms, physical limitations, quality of life, and social limitations. Graded on a scale of 0 to 100, a 5-point change in either direction is considered significant.

He explained that researchers first divided a cohort of patients into 3 groups based on the their KCCQ responses at baseline. Across both the primary end point and 5 secondary end points—which included elements of the primary end point and death from any cause — dapagliflozin produced benefits for all 3 groups, regardless of their symptoms and quality of life score before starting the medication.

Next, he showed that more dapagliflozin patients had KCCQ score increases of 5 points, of 10 points, and of 15 points than those taking placebo, and fewer taking dapagliflozin saw their scores go down.

A separate analysis, presented in the late-breaking session by Felipe Martinez, MD, professor of medicine, Cordoba National University in Argentina, found that the HF benefits of the SGLT2 inhibitor were not only consistent when added to background medication taken by adults age 65 and older,² but that “The absolute benefits in older patients were large because they were at higher risk than younger patients.”

Senior author John J.V. McMurray, BSc (Hons), MB ChB (Hons), MD, FRCP, FESC, FACC, FAHA, FRSE, FMedSci, professor of medical cardiology and deputy director of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow, United Kingdom, who outlined the findings in the press conference, said concerns about polypharmacy and tolerability can lead to seniors not receiving novel therapy, despite the benefits it can offer. This is especially true when older patients have HF, he said, because these patients tend to many comorbidities—and thus are on many medications.

First, McMurray presented the primary outcome of older adults by age group:

• The hazard ratio (HR) for adults <55 years of age was 0.87 (0.60, 1.28).
• For those 55-64 years of age, the HR 0.71 (0.55, 0.93).
• For those 65-74 years of age, the HR 0.76 (0.61, 0.95)
• For those ≥75 years of age, the HR was 0.68 (0.53, 0.88).

McMurray noted that going in, there was concern that the mechanism of an SGLT2 inhibitor would cause volume depletion among elderly adults, but among the oldest age groups, there were more of these incidents in the placebo group than those taking dapagliflozin.

Both sets of results were simultaneously published in the journal Circulation, the official publication of the American Heart Association.^1,2

In her comments, Lam discussed the growing importance of PROs and how they will fit into treatment going forward. “Will PRO data help us in treatment selection and sequencing? If so, which PRO tool? Which KCCQ domains?” she asked. “Finally, what are the challenges to implementation?"

1. Kosiborod MN, Jhund P, Docherty KF, et al. Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction [published online November 17, 2019]. Circulation. doi: 10.1161/CIRCULATIONAHA.119.044138.

2. Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and safety of dapagliflozin in HFrEF according to age: insights from DAPA-HF [published online November 17, 2019]. Circulation. doi: 10.1161/CIRCULATIONAHA.119.044133.

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