Meeting NewsPerspective

Dapagliflozin confers consistent benefit in HF without diabetes: DAPA-HF

John J.V. McMurray

PHILADELPHIA — New analyses of the DAPA-HF trial suggest that the benefits of the SGLT2 inhibitor dapagliflozin extend beyond its effects as a type 2 diabetes therapy.

On the heels of the main DAPA-HF results presented at the European Society of Cardiology Congress in September, John J.V. McMurray, MD, professor of cardiology at the Institute of Cardiovascular and Medical Sciences at University of Glasgow, Scotland, presented new data that confirm benefits of treatment with dapagliflozin (Farxiga, AstraZeneca) 10 mg once daily in patients with HF with reduced ejection fraction and no type 2 diabetes.

Over a median follow-up of 18 months, dapagliflozin showed benefit for the primary outcome of CV death or worsening HF, with a 27% relative risk reduction in patients without diabetes (HR = 0.73; 95% CI, 0.6-0.88) compared with 25% in patients with diabetes (HR = 0.75; 95% CI, 0.63-0.9; P for interaction = .8).

“Even in patients without diabetes, you see very early separation [of the primary outcome curves] — a rapidly developing benefit of dapagliflozin compared to placebo,” McMurray said during a press conference.

Additional results presented show similar results for secondary outcomes, including:

  • CV death or HF hospitalization: 27% relative risk reduction in patients without diabetes (HR = 0.73; 95% CI, 0.6-0.89) and 25% relative risk reduction in patients with diabetes (HR = 0.75; 95% CI, 0.63-0.9); P for interaction = .83.
  • Total HF hospitalizations and CV death, including first and repeat hospitalizations: rate ratio = 0.73 (95% CI, 0.59-0.91) in patients without diabetes and 0.77 (95% CI, 0.63-0.94) in patients with diabetes; P for interaction = .74.
  • Clinically meaningful change (at least 5 points) in Kansas City Cardiomyopathy Questionnaire Total Symptom Score: OR for improvement = 1.12 (95% CI, 1.03-1.22) for patients without diabetes and 1.2 (95% CI, 1.09-1.31) for patients with diabetes; P for interaction = .74)
  • Worsening renal function, defined as a sustained 50% reduction in estimated glomerular filtration rate, end-stage renal disease or death from renal causes: HR = 0.67 (95% CI, 0.3-1.49) for patients without diabetes and 0.73 (95% CI, 0.39-1.34) for patients with diabetes; P for interaction = .86.
  • All-cause death: 12% relative reduction in patients without diabetes (HR = 0.88; 95% CI, 0.7-1.12) and 22% relative reduction in patients with diabetes (HR = 0.78; 95% CI, 0.63-0.97); P for interaction = .45.

“The relative and absolute risk reductions in death and hospitalization were substantial, clinically important, and consistent in patients with and without type 2 diabetes,” McMurray said.

In other results, treatment effect did not differ by diabetes status or HbA1c level.

“Even in patients with a completely normal HbA1c, we can see a similar benefit of dapagliflozin over placebo,” he said.

Dapagliflozin was well tolerated and the rate of treatment discontinuation was low in patients with and without diabetes. Hypoglycemia and diabetic ketoacidosis developed only in patients with diabetes, McMurray said.

“We feel that this really is quite strong evidence that dapagliflozin, which was recently introduced as a diabetes drug, clearly is a drug that is beneficial in heart failure, including in patients with heart failure who do not have type 2 diabetes,” he said.

Reference:

McMurray JJV. Late Breaking Science I. Outside the Box: New Approaches to CVD Risk Reduction. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.

Disclosures: The DAPA-HF study was funded by AstraZeneca. McMurray reports his institution has been paid by AstraZeneca for his time spent as principal investigator for DAPA-HF and for advisory boards related to dapagliflozin, diabetes and HF.

John J.V. McMurray

PHILADELPHIA — New analyses of the DAPA-HF trial suggest that the benefits of the SGLT2 inhibitor dapagliflozin extend beyond its effects as a type 2 diabetes therapy.

On the heels of the main DAPA-HF results presented at the European Society of Cardiology Congress in September, John J.V. McMurray, MD, professor of cardiology at the Institute of Cardiovascular and Medical Sciences at University of Glasgow, Scotland, presented new data that confirm benefits of treatment with dapagliflozin (Farxiga, AstraZeneca) 10 mg once daily in patients with HF with reduced ejection fraction and no type 2 diabetes.

Over a median follow-up of 18 months, dapagliflozin showed benefit for the primary outcome of CV death or worsening HF, with a 27% relative risk reduction in patients without diabetes (HR = 0.73; 95% CI, 0.6-0.88) compared with 25% in patients with diabetes (HR = 0.75; 95% CI, 0.63-0.9; P for interaction = .8).

“Even in patients without diabetes, you see very early separation [of the primary outcome curves] — a rapidly developing benefit of dapagliflozin compared to placebo,” McMurray said during a press conference.

Additional results presented show similar results for secondary outcomes, including:

  • CV death or HF hospitalization: 27% relative risk reduction in patients without diabetes (HR = 0.73; 95% CI, 0.6-0.89) and 25% relative risk reduction in patients with diabetes (HR = 0.75; 95% CI, 0.63-0.9); P for interaction = .83.
  • Total HF hospitalizations and CV death, including first and repeat hospitalizations: rate ratio = 0.73 (95% CI, 0.59-0.91) in patients without diabetes and 0.77 (95% CI, 0.63-0.94) in patients with diabetes; P for interaction = .74.
  • Clinically meaningful change (at least 5 points) in Kansas City Cardiomyopathy Questionnaire Total Symptom Score: OR for improvement = 1.12 (95% CI, 1.03-1.22) for patients without diabetes and 1.2 (95% CI, 1.09-1.31) for patients with diabetes; P for interaction = .74)
  • Worsening renal function, defined as a sustained 50% reduction in estimated glomerular filtration rate, end-stage renal disease or death from renal causes: HR = 0.67 (95% CI, 0.3-1.49) for patients without diabetes and 0.73 (95% CI, 0.39-1.34) for patients with diabetes; P for interaction = .86.
  • All-cause death: 12% relative reduction in patients without diabetes (HR = 0.88; 95% CI, 0.7-1.12) and 22% relative reduction in patients with diabetes (HR = 0.78; 95% CI, 0.63-0.97); P for interaction = .45.

“The relative and absolute risk reductions in death and hospitalization were substantial, clinically important, and consistent in patients with and without type 2 diabetes,” McMurray said.

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In other results, treatment effect did not differ by diabetes status or HbA1c level.

“Even in patients with a completely normal HbA1c, we can see a similar benefit of dapagliflozin over placebo,” he said.

Dapagliflozin was well tolerated and the rate of treatment discontinuation was low in patients with and without diabetes. Hypoglycemia and diabetic ketoacidosis developed only in patients with diabetes, McMurray said.

“We feel that this really is quite strong evidence that dapagliflozin, which was recently introduced as a diabetes drug, clearly is a drug that is beneficial in heart failure, including in patients with heart failure who do not have type 2 diabetes,” he said.

Reference:

McMurray JJV. Late Breaking Science I. Outside the Box: New Approaches to CVD Risk Reduction. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.

Disclosures: The DAPA-HF study was funded by AstraZeneca. McMurray reports his institution has been paid by AstraZeneca for his time spent as principal investigator for DAPA-HF and for advisory boards related to dapagliflozin, diabetes and HF.

    Perspective
    Darren K. McGuire

    Darren K. McGuire

    I’ve been working in this intersection of diabetes and heart disease for 25 years. The SGLT2 inhibitors and GLP-1 receptor agonists are really impacting CV outcomes and now we have to figure out how to get them into the hands of the cardiologists. Trials like DAPA-HF are resetting and refining ideas about how these drugs might be effective for CV health. DAPA-HF shows dapagliflozin clearly carries that benefit into the population without diabetes. The learnings from these trials have really focused our attention on HF. DAPA-HF is the first of many ongoing trials in HF patients both with and without diabetes, and with preserved and reduced ejection fraction. Separate to that is the effect on the kidney in patients with and without diabetes.

    The overall message is that although these drugs were initially designed to treat patients with type 2 diabetes, it is clear there are CV benefits unrelated to the glucose effects. These therapies have squarely been placed into the cardiology medical domain. We now have to, as a community, learn to prescribe them and begin applying the data as quick as we can.

    • Darren K. McGuire, MD, MHSc
    • Cardiology Today Editorial Board Member
      University of Texas Southwestern Medical Center

    Disclosures: McGuire reports he has relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Lexicon, Novo Nordisk and Sanofi.

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