medwireNews: Extrapolation of results from the DAPA-HF trial suggests that lifetime use of dapagliflozin will provide continuing benefits for people with heart failure and reduced ejection fraction (HFrEF).
As reported in JAMA Cardiology, the exploratory analysis included data from 4744 participants of the DAPA-HF trial who were randomly assigned to receive dapagliflozin 10 mg/day or placebo in addition to standard care and were followed up for an average of 17.6 months. The team used actuarial methods to project the long-term treatment outcomes of participants treated with dapagliflozin versus placebo.
“Clinical trials rarely have a duration of follow-up adequate to permit estimation of the extension of event-free survival over a person’s lifetime,” but “[u]sing this approach, it is possible to provide patients in specific age categories with their extrapolated years of life gained and years free of a nonfatal worsening HF event or death from cardiovascular causes,” explain John McMurray (University of Glasgow, UK) and co-investigators.
For the primary composite outcome of cardiovascular death or a worsening HF event, the researchers estimated that a person aged 65 years has an extrapolated average event-free survival time of 8.3 years when treated with dapagliflozin versus 6.2 years when treated with placebo, a significant gain of 2.1 years with the sodium-glucose cotransporter (SGLT)2 inhibitor.
They say that the average event-free survival time was longer with dapagliflozin versus placebo in people of all ages studied, with the extrapolated gain ranging from 3.0 years in someone aged 45 years to 1.6 years for someone aged 80 years.
Similarly, the mean extrapolated life expectancy was longer for people treated with dapagliflozin than those given placebo, with projected survival gains ranging from 2.6 years in those aged 45 years to 1.1 years in those aged 80 years.
“These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival” and this information “may be helpful in communicating the benefits of this treatment to patients with HFrEF,” say McMurray and team.
Writing in an accompanying commentary, Laine Elliott Thomas (Duke University, Durham, North Carolina, USA) and colleagues say that the study results “have the potential to improve patient-clinician conversations around expected benefits of treatment,” and, if accurate, they “reinforce the importance of long-term adherence to therapy.”
The commentators note, however, that the findings should be interpreted with caution because it is not known whether the efficacy of dapagliflozin remains consistent over time. They also point out a number of practical considerations that “must be taken into account when evaluating the potential accuracy of extrapolated event rates and treatment effects,” including long-term treatment adherence and the development of comorbidities that would make people ineligible for dapagliflozin treatment based on trial inclusion criteria.
“Whenever feasible, long-term follow-up should be incorporated into clinical trials or assessed in other data sources, such as clinical registries,” Thomas and co-authors conclude.
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