SGLT2 Inhibitor Adds Years of Life to Patients With Heart Failure

Patients with heart failure with reduced ejection fraction (HFrEF) may increase their lifespan if they take the SGLT2 inhibitor dapagliflozin (Farxiga) over the long term, a statistical modeling study showed.

Mean event-free survival was an estimated 8.3 years in a patient with HFrEF who started dapagliflozin at age 65. As a similar patient on standard therapy alone would only be expected to live free from heart failure events for another 6.2 years, this represented an event-free survival time gain of 2.1 years (P=0.002).

Gains in event-free survival were an estimated 3.0 years for a patient age 55 and 1.2 years for a patient age 75, reported John McMurray, MD, of the British Heart Foundation Cardiovascular Research Centre at the University of Glasgow, and colleagues in a study published online in JAMA Cardiology.

Ultimately, statistical projections determined that overall life expectancy could be extended by 2.6 years for a person age 45, by 1.7 years for a person age 65, and by 1.1 years for a person age 80 with dapagliflozin therapy.

This study was a post-hoc analysis of the DAPA-HF trial, which found that dapagliflozin reduced worsening heart failure events and cardiovascular deaths in patients with HFrEF, regardless of diabetes status.

“In DAPA-HF, dapagliflozin also improved symptoms and functional limitations due to HF [heart failure], indicating that longer event-free and overall survival would likely be accompanied by improved quality of life,” McMurray’s group noted.

DAPA-HF included 4,744 participants (76.6% men, mean age 66.3 years) who were randomized to dapagliflozin 10 mg once daily or placebo atop standard therapy.

A major limitation of the trial was that HFrEF patients were enrolled in 2017-2018, and mean follow-up was a mere 17.6 months.

Thus, in lieu of long-term follow-up data, the study authors relied on age-specific actuarial methods for long-term extrapolation in an exploratory analysis.

“These findings are consistent with previously reported HRs and have the potential to improve patient-clinician conversations around expected benefits of treatment. If accurate, these findings reinforce the importance of long-term adherence to therapy,” wrote JAMA Cardiology editors led by Laine Thomas, PhD, of Duke University in Durham, North Carolina, in an invited commentary.

Nevertheless, Thomas and co-authors urged caution in interpreting these statistical projections.

“These methods leverage the fact that event rates change over a lifetime, largely due to increasing age, and impose the assumption that other aspects of time (e.g., duration of treatment) do not matter. That is, for any given age, the hazard of an event (i.e., the instantaneous probability of events) is constant regardless of time receiving treatment,” they explained.

McMurray and colleagues acknowledged that they could not account for people developing cancer, diabetes, severe kidney disease, or other long-term changes in health status.

Long-term follow-up therefore remains invaluable and “should be incorporated into clinical trials or assessed in other data sources, such as clinical registries” whenever feasible, Thomas and team concluded.

In 2020, dapagliflozin became the first SGLT2 inhibitor approved for HFrEF treatment. The biological mechanisms that underpin the drug’s cardio-renal benefits remain under investigation.