Dapagliflozin Reduces First, Recurrent Event Risk in DAPA-HF

Piotr Ponikowski, MD, PhD

In an additional analysis of the Dapagliflozin in Patients Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial, investigators found the SGLT2 inhibitor reduced treated patients’ likelihood of first and recurrent hospitalizations due to heart failure (HF) over 18 months.

The assessment, in which dapagliflozin (Farxiga) was compared to placebo in composite HF hospitalizations or cardiovascular-related deaths from the DAPA-HF study, was presented virtually at the ACC.20 Together with Word Congress of Cardiology (ACC/WCC) Scientific Sessions.

Led by Piotr Ponikowski, MD, PhD, of the Center for Heart Disease at University Hospital, Medical University in Wroclaw, Poland, investigators conducted the pre-specified secondary analysis to understand the therapy’s benefit for event risk reduction.

Ponikowski, who reports personal and institutional fees from AstraZeneca relevant to the study, explained that patients with HF are likely to experience >1 hospitalization during their disease course. Despite this, conventional analyses generally consider time-to-first event—not overall composite risk of events.

“Time-to-first event may also overestimate treatment benefit if effect wanes over time, or if a subset of patients does not respond to therapy and experiences recurrent events,” investigators wrote. “We assessed the effect of dapagliflozin on total events (first and recurrent) in DAPA-HF.”

The team assessed first and recurrent event data from the 4600-plus patients enrolled to either once-daily dapagliflozin 10 mg (n = 2371) or placebo (n = 2373) in DAPA-HF. In assessing for a primary endpoint of cardiovascular death or worsening HF event (defined as unplanned hospitalization or an urgent HF visit requiring intravenous therapy), they found ≥844 composite endpoint events over a median 18.2-month follow-up.

In their time-to-first event analysis, Ponikowski and colleagues found a 30% risk reduction of first HF hospitalization with dapagliflozin (HR 0.70; 95% CI, 0.59-0.83; P <.0001), and a 28% reduction in cardiovascular death risk (HR, 0.82; 95% CI, 0.69-0.98; P = .029).

Of the 548 patients to be hospitalized due to HF at least once during DAPA-HF, 380 (69.3%) were admitted only once. Another 110 (20.1%) were hospitalized twice, and the remaining 58 (10.6%) were hospitalized ≥3 times.

Patients treated with dapagliflozin made up 41.9% of those hospitalized at least once due to HF, and 42% of total hospitalizations. The therapy associated with a 25% reduced first of time to first HF hospitalization or cardiovascular death (HR, 0.75; 95% CI, 0.65-0.85; P <.0001) versus placebo.

Because of the total rate of events being higher than the time-to-first event rate, the absolute risk reduction for total events was even more pronounced: 5.3 vs 3.9 fewer events per 100 person years of follow-up. Patients treated with dapagliflozin reported a 28% reduced risk of all HF hospitalizations compared to placebo over 18 months (HR, 0.72; 95% CI, 0.59-0.86).

Ponikowski and colleagues noted that conventional time-to-first analysis of DAPA-HF would have not accounted for about 40% of all events to have actually occurred in patients. Even with faring well in time-to-first HF event risk reduction, dapagliflozin was associated an even greater absolute risk reduction when accounting for these supplemental events.

The study, “Benefit of Dapagliflozin on First and Repeat Events in Patients with HFrEF in DAPA-HF,” was presented at ACC 2020.