• Dapagliflozin Benefits HFrEF Outcomes, Even Without Diabetes

    DAPA-HF trial affirms similar benefit to diabetes drug regardless of type 2 diabetes status

    PARIS -- Dapagliflozin (Farxiga) lowered the risk of cardiovascular death and decompensation, and improved symptoms in heart failure (HF) with reduced ejection fraction (HFrEF), the DAPA-HF trial found.

    Dapagliflozin reduced risk of cardiovascular death and worsening HF, as indicated by urgent HF visits or HF hospitalization, by a relative 26% compared with placebo (16.3% vs 21.2%, HR 0.74, 95% CI 0.65-0.85), reported John McMurray, MD, of the University of Glasgow, at the European Society of Cardiology (ESC) congress.

    The effect size was nearly identical between the 45% of patients with type 2 diabetes at baseline and those without (HR 0.75, 95% CI 0.63-0.90, vs HR 0.73, 95% CI 0.60-0.88), the investigators found.

    "The relative and absolute risk reductions in death and hospitalization were substantial, clinically important, and consistent across important subgroups, including patients without type 2 diabetes," McMurray said, adding that the trial included both populations, because "we thought this was a heart failure drug, not a diabetes drug."

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    John McMurray, MD, discusses the DAPA-HF data at a press briefing

     

    "This is the first new class of drug in systolic heart failure for some years, and will undoubtedly lead to a change in guidelines and clinical practice," said Martin Cowie, MD, of the Imperial College London in England, who was not involved in the trial.

    "A new pillar of treatment is exciting, but will require education to ensure doctors understand the benefits and how to discuss this option with their patients. It is also exciting that the tolerability of this drug appears good," he told MedPage Today.

    But "We still do not know the mechanism of action," noted ESC session discussant Marco Metra, MD, of Università degli Studi in Brescia, Italy. Possible mechanisms include a diuretic effect, ion fluxes, adipokines, myocardial metabolism, and fibrosis, he added.

    Metra also pointed out the results of the trial are comparable to those of recent positive trials of pharmacological therapy in HFrEF.

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to prevent cardiovascular disease largely by preventing HF rather than atherosclerotic events, noted Donald Lloyd-Jones, MD, of Northwestern University in Chicago.

    "The reason they prevent heart failure for the most part is that they are good diuretics," Lloyd-Jones told MedPage Today.

    McMurray's group assessed 2,373 patients in the dapagliflozin group and 2,371 in the placebo group. The cohort had a mean age of about 67 and was about 77% male. Median follow-up was 18.2 months. Patients had to have an HF diagnosis for at least 2 months. All participants were in New York Heart Association functional class ≥II, were optimally treated with device and pharmacological therapy for HF, and had a left ventricular ejection fraction (LVEF) recorded to be ≤40% within the last year.

    Along with standard therapy, placebo or 10 mg of dapagliflozin once per day were administered to patients with HFrEF both without and with type 2 diabetes.

    Among the components of the primary endpoint, the findings showed the following for dapagliflozin versus placebo:

    • Occurrence of urgent HF visit or HF hospitalization: 10.0% vs 13.7%
    • Cardiovascular death: 9.6% vs 11.5%
    • HF hospitalization: 9.7% vs 13.4%
    • HF hospitalization or cardiovascular death: 16.1% vs 20.9%
    • Death from any cause: 11.6% vs 13.9%

     

    Other data showed a total symptom score change on the 100-point Kansas City Cardiomyopathy Questionnaire (KCCQ), for which higher values indicate better quality of life, from baseline to 8 months of +6.1 for the dapagliflozin group and +3.3 for placebo (difference 2.8 points, 95% CI 1.6-4.0).

    Key inclusion criteria of the trial were LVEF ≥40%, symptomatic HF, NT-proBNP of at least 600 pg/mL, and if hospitalized for HF within the last year, atrial fibrillation or flutter of at least 900 pg/mL, and NT-proBNP of ≥400 pg/mL.

    Key exclusion criteria were: type 1 diabetes mellitus, estimated glomerular filtration rate under 30 ml/min/1.73 m2, systolic blood pressure <95 mm Hg, and symptomatic hypotension.

     

    McMurray disclosed a relevant relationship (institutional) with AstraZeneca.

    Cowie disclosed relevant relationships with AstraZeneca.

    Lloyd-Jones disclosed no relevant relationships with industry.

    Metra disclosed relevant relationships with Amgen, Bayer, Fresenius, LivaNova, Novartis, Servier, and Vifor, as well as being a member of the executive committee of SOLOIST-HF.

    Source:

    European Society of Cardiology

    Source Reference: McMurray J "Dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF)" ESC 2019.

    European Society of Cardiology

    Source Reference: Metra M, "DAPA-HF: Discussant review" ESC 2019.

    Read the original article on Medpage Today: Dapagliflozin Benefits HFrEF Outcomes, Even Without Diabetes

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