06 Sep Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure

MedicalResearch.com Interview with:

Prof. John McMurray

Prof. John McMurray
Professor of Cardiology
Institute of Cardiovascular & Medical Sciences
University of Glasgow

MedicalResearch.com: What is the background for this study?

Response: SGLT2 inhibitors prevent the development of heart failure (HF) in patients with type 2 diabetes (T2D) – can they be used to treat patients with established heart failure? Also, although introduced as a glucose-lowering treatment for T2D, experimental evidence suggests these drugs may have non-glucose mediated benefits. So, might they be a treatment for HF even in patients without diabetes? 

MedicalResearch.com: What are the main findings?

Response: Over a median follow-up of 18.2 months, the primary outcome occurred in 386 of 2,373 patients (16.3%) in the dapagliflozin group and in 502 of 2,371 patients (21.2%) in the placebo group (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.65–0.85; p<0.00001).The components of the primary outcome were also analysed separately. A total of 237 patients (10.0%) receiving dapagliflozin and 326 patients (13.7%) receiving placebo experienced a first episode of worsening heart failure (HR 0.70; 95% CI 0.59–0.83; p<0.00004) and 227 (9.6%) and 273 (11.5%), respectively, died from cardiovascular causes (HR 0.82; 95% CI 0.69–0.98; p=0.029).

Patients symptoms were improved significantly and all-cause mortality was reduced, significantly, by 17%. Regarding side effects, 178 patients (7.5%) in the dapagliflozin group had an adverse event related to volume depletion compared to 162 (6.8%) in the placebo group, with no significant difference between groups. Adverse events related to renal dysfunction occurred in153 patients (6.5%) in the dapagliflozin group versus 170 patients (7.2%) in the placebo group, with no significant difference between groups. Major hypoglycaemia and lower limb amputation and fracture were infrequent and occurred at similar rates in the two treatment groups.

MedicalResearch.com: How does a SGLT2 inhibitor work in patients without diabetes?

Response: In addition to diuretic and related hemodynamic actions of SGLT2 inhibitors, effects on myocardial metabolism, ion transporters, fibrosis, adipokines and uric acid have also been proposed. Most of these actions, as well as preservation of renal function, would also presumably benefit patients with established heart failure, including those without diabetes, in which SGLT2 inhibitors have not been tested. 

MedicalResearch.com: What should readers take away from your report?

Response: Dapagliflozin represents a completely novel treatment for heart failure, working in a different way than other treatments. It does everything we would like an ideal treatment for heart failure to do – increase survival, reduce hospital admission and improve symptoms. Moreover, it has these benefits in addition to/on top of existing effective therapies

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Does dapagliflozin work in the other principal heart failure phenotype – heart failure with preserved ejection fraction?

Disclosures: The commentator at our presentation suggested this trial is a major breakthrough, heralding a new era in HF therapy. y employer, Glasgow University, was paid for my role as principal investigator in DAPA-HF. 

Citation:

THE DAPAGLIFLOZIN AND PREVENTION OF ADVERSE-OUTCOMES IN HEART FAILURE TRIAL

ESC 2019 presentation

http://www.crtonline.org/presentation-detail/dapa-hf-dapagliflozin-prevention-of-adverse-outcom

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Last Updated on September 6, 2019 by Marie Benz MD FAAD