Support for add-on dapagliflozin use in HF patients of all ages
medwireNews: A post-hoc analysis of data from the DAPA-HF trial indicates that the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin has consistent efficacy and safety profiles among people with heart failure and reduced ejection fraction (HFrEF) across a range of age categories.
These findings are in accordance with the main trial findings, reported previously by medwireNews, which demonstrated that the addition of dapagliflozin 10 mg/day to standard drug and device therapy reduced the risk for the composite primary outcome of cardiovascular death, heart failure hospitalization, or an urgent heart failure hospital visit by 26% over a median follow-up of 18.2 months.
Felipe Martinez (Córdoba National University, Argentina), who presented the post-hoc analysis at the American Heart Association Scientific Sessions 2019 conference in Philadelphia, Pennsylvania, USA, said that the latest findings support the use of add-on dapagliflozin as “a new approach to the treatment of HFrEF, irrespective of age.”
As reported by Martinez and published simultaneously in Circulation, dapagliflozin significantly reduced the risk for the composite primary outcome relative to placebo in all age groups studied, with a risk reduction of 13% for the 636 participants aged less than 55 years, 29% for the 1242 patients aged 55–64 years, 24% for the 1717 aged 65–74 years, and 32% for the 1149 aged 75 years or older.
When the components of the endpoint were analyzed separately, Martinez reported that “the relative and absolute risk reductions in death and hospitalization were substantial and clinically important,” with greater absolute benefits in older patients due to them being at higher risk for these outcomes.
For instance, rates of heart failure hospitalization or an urgent heart failure hospital visit were 7.7 and 7.5 per 100 person–years with dapagliflozin and placebo, respectively, for those aged less than 55 years (hazard ratio [HR]=1.05), rising to a corresponding 8.0 and 12.1 per 100 person–years for those aged 75 years and older (HR=0.64).
Martinez said that dapagliflozin was well tolerated in all age groups, which is important because “tolerability is a particular concern in the elderly, not only because of advanced age and comorbidity, but also because of polypharmacy.”
Rates of serious adverse events (AEs; including death) and AEs leading to permanent treatment discontinuation increased with increasing age, but were comparable among patients treated with dapagliflozin versus placebo in all age categories.
For participants aged less than 55 years, 32.7% of those in the dapagliflozin arm and 34.2% of those given placebo experienced serious AEs, while 2.9% and 3.4%, respectively, experienced serious AEs leading to treatment discontinuation. The corresponding rates in people aged 75 years and older were 42.8% versus 49.4% and 5.8% versus 5.9%. Individuals treated with dapagliflozin did not have an elevated risk for renal dysfunction or volume depletion compared with those given placebo, and these findings were consistent across all age categories.
Writing in an editorial accompanying the publication in Circulation, G Michael Felker (Duke University School of Medicine, Durham, North Carolina, USA) says that these safety data “emphasize another potentially attractive feature of SGLT2 [inhibitors] as heart failure therapy—these agents generally ‘play well with others’ when it comes to overlapping intolerances that often limit (either in reality or in perception) optimization of GDMT [guideline-directed medical therapy].”
He adds that SGLT2 inhibitors “generally lack some of the other dose limiting adverse effects (such as renal dysfunction, hyperkalemia, and hypotension) that can make aggressive uptitration of GDMT problematic, particularly in older patients or those with more advanced disease.”
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