01 Apr Benefit in Heart Failure Demonstrates Dapagliflozin – FARXIGA is Not Just a Diabetes Drug
MedicalResearch.com Interview with:
John J. V. McMurray, MD FRCP FESC FACC FAHA FRSE FMedSci
British Heart Foundation Cardiovascular Research Centre
University of Glasgow
Glasgow, United Kingdom
Kieran F Docherty
British Heart Foundation Cardiovascular Research Centre,
University of Glasgow
MedicalResearch.com: What is the background for this study?
Response: DAPA-HF was a double-blind randomized controlled trial comparing dapagliflozin 10 mg once daily with placebo in 4744 patients with heart failure and reduced ejection fraction (HFrEF).
The primary outcome was a composite of time to occurrence of a worsening heart failure event (principally heart failure hospitalization) or cardiovascular death, whichever came first.
Dapagliflozin reduced the primary outcome by 26% and reduced the risk of each of heart failure hospitalization and cardiovascular death individually, as well as overall mortality. Patient symptoms were also improved.
The aim of the present report was to examine the effect of dapagliflozin separately in patients with and without type 2 diabetes at baseline (45/55% split in the trial). The reason for this was that dapagliflozin was originally introduced as a glucose-lowering medication for the treatment of type 2 diabetes. We find that dapagliflozin was equally beneficial in patients with and without diabetes and was as well tolerated in patients without diabetes as in those with diabetes. More remarkably, among the patients without diabetes, dapagliflozin was as effective in participants with a completely normal glycated haemoglobin (HbA1c) as in those with prediabetes. In patients with a normal HbA1c, dapagliflozin did not lead to any reduction in HbA1c, but did improve clinical outcomes.
MedicalResearch.com: What are the main findings?
Response: We find that dapagliflozin was equally beneficial in patients with and without diabetes and was as well tolerated in patients without diabetes as in those with diabetes.
More remarkably, among the patients without diabetes, dapagliflozin was as effective in participants with a completely normal glycated haemoglobin (HbA1c) as in those with prediabetes. In patients with a normal HbA1c, dapagliflozin did not lead to any reduction in HbA1c, but did improve clinical outcomes.
MedicalResearch.com: What should readers take away from your report?
Response: These findings show 2 key things:
1) Dapagliflozin is not just a diabetes drug – it is clearly a treatment for HFrEF too.
2) The beneficial effect of dapagliflozin on cardiovascular outcomes is not explained by glucose lowering.
Therefore, even though dapagliflozin was originally introduced as a glucose-lowering therapy for type 2 diabetes, it clearly has a much broader therapeutic role. Indeed, it is one of the most effective treatments for heart failure that we have seen in many years. The recent news that Data Monitoring Committee recommended stopping DAPA-CKD early for efficacy supports the view that this class of drugs have wider therapeutic benefits.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: These exciting results raise the question of whether dapagliflozin might also be beneficial in the other major type of heart failure, that is heart failure with preserved ejection fraction (HFpEF). There are two large trials currently underway establishing whether SGLT2 inhibitors are effective in this other heart failure phenotype.
Disclosures: DAPA-HF was funded by AstraZeneca ,my employer, Glasgow University, was paid for my time working on the trial.
Petrie MC, Verma S, Docherty KF, et al. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.1906
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