Based on the results of the DAPA-HF study, Swissmedic has approved dapagliflozin for the treatment of heart failure with reduced ejection fraction (HFrEF), whether or not patients have type 2 diabetes. The SGLT-2 inhibitor significantly reduced the risk of cardiovascular mortality and worsening heart failure in HFrEF patients as an add-on to standard therapy.
The indication extension decided by Swissmedic took place on July 2, 2020 as part of a fast track procedure. Thus, dapagliflozin (Forxiga®), previously used exclusively for the treatment of type 2 diabetes (T2D), has recently become the first and only SGLT-2 inhibitor* to be used in non-diabetics for the treatment of heart failure with reduced ejection fraction (HFrEF, NYHA class II-IV, LVEF ≤40%) [1]. Heart failure affects about 64 million people worldwide, with about half of them having reduced ejection fraction. It is a chronic and degenerative disease that causes half of patients to die within five years of diagnosis [2–4]. In individuals aged 65 years and older, heart failure is the leading cause of hospitalizations [5]. The indication expansion for Forxiga® is based on the positive results from the landmark Phase III DAPA-HF study (box) published in the New England Journal of Medicine.
* SGLT-2 inhibitor = sodium-glucose cotransporter-2 inhibitor
| DAPA-HF Study DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) is an international, multicenter, randomized, double-blind, parallel-group study in 4744 patients with heart failure and reduced ejection fraction (LVEF ≤40%, NYHA II-IV) with and without T2D to assess the effect of Forxiga® 10 mg (administered once daily in addition to standard therapy) compared with placebo. The primary composite end point is time to first worsening of heart failure (ie, hospitalization or a comparable event, such as an urgent visit) or cardiovascular-related death. The median observation period is 18.2 months [6]. |
Milestone for patients with HFrEF
Dapagliflozin (Forxiga®) reduced the risk of the composite endpoint of cardiovascular mortality or worsening heart failure** by 26% in patients HFrEF versus placebo in the DAPA-HF study as an add-on to standard therapy.
#
. Over a relatively short median study duration of 18.2 months, an NNT (number needed to treat) of only 21 was achieved for the primary endpoint. Furthermore, Forxiga® resulted in statistically significant improvements in KCCQ*** total symptom score at 8 months compared to placebo (+6.1 vs. +3.3 points) [6]. The KCCQ score is a patient-completed questionnaire that measures patients’ symptoms and health status and has been validated by the FDA as a reliable measure of health status in patients with heart failure [7]. The safety profile of Forxiga® in the DAPA-HF study was consistent with the previously reported safety profile of the drug [6]. It is important to emphasize that the rates of hypoglycemia and hypotension in the group of patients without type 2 diabetes were at placebo level [8]. With a once-daily dosage of 10 mg, without titration, Forxiga® offers seamless integration into any heart failure treatment regimen to optimize therapy. No change in existing heart failure medication is required [1]. Further empirical findings on the efficacy of Forxiga® in patients with heart failure were provided by the DECLARE cardiovascular outcomes trial, in which the SGLT-2 inhibitor, as an add-on to standard therapy, reduced the risk of the composite endpoint of hospitalization for heart failure or cardiovascular death in adults with T2D compared with placebo [9]. Based on these data, Swissmedic had decided in April 2020 to expand the indication to prevent hospitalizations for heart failure or cardiovascular death in type 2 diabetic patients [1].
Source: AstraZeneca AG
** Worsening heart failure was defined as hospitalizations or emergency medical contact due to heart failure requiring subsequent intervenous therapy.
# absolute risk reduction (ARR) = 4.9% (event rate/100 patient-years: 11.6 vs. 15.6); p<0.0001
*** KCCQ = Kansas City Cardiomyopathy Questionnaire
Literature:
- Technical Information Forxiga®, www.swissmedicinfo.ch, as of July 2020.
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- McMurray JJV, et al: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995-2008.
- Green CP, et al: Development and Evaluation of the Kansas City Cardiomyopathy Questionnaire: A New Health Status Measure for Heart Failure. Journal of the American College of Cardiology 2000; 35(5): 1245-1255.
- Petrie MC, et al: Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA 2020; 323(14): 1353-1368.
- Wiviott SD, et al: Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380(4): 347-357.
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