Safia Chatur, MD: Effect of Dapagliflozin on Worsening Heart Failure

A new analysis of the DELIVER trial indicated hospitalization as a first presentation of worsening heart failure in patients with heart failure with mildly reduced or preserved ejection fraction was significantly associated with subsequent mortality.

Presented at the European Society of Cardiology Congress 2023, results from the secondary analysis of the DELIVER trial showed oral diuretic intensification in ambulatory care was common, adversely prognostic, and ultimately, significantly reduced by treatment with dapagliflozin.

“Importantly, treatment with dapagliflozin significantly reduced the full spectrum of worsening heart failure events, including outpatient oral diuretic intensification,” said presenting author Safia Chatur, MD, an echocardiography fellow, Massachusetts General Hospital, Harvard Medical School, in an interview with HCPLive. “The inclusion of outpatient oral diuretic intensification in a broader composite worsening heart failure endpoint led to an important increment in a number of clinical events. This may have implications for future clinical trial design.”

Hospitalization is a known sentinel event in the disease trajectory of heart failure; however, not all who experience decompensation are hospitalized. The intensification of outpatient diuretic use is common in response to worsening symptoms indicative of heart failure, but its clinical relevance is less understood.

The DELIVER trial was a global, randomized clinical trial of dapagliflozin compared to placebo in 6263 participants with heart failure with mildly reduced or preserved ejection fraction. This analysis, led by Chatur, assessed the association between various non-fatal worsening heart failure events and rates of subsequent mortality.

The analysis defined diuretic intensification as new initiation or dose up-titration sustained for ≥30 days. Investigators also assessed the treatment effect of dapagliflozin on a composite endpoint of cardiovascular death, heart failure hospitalization, urgent heart failure visits, or outpatient oral diuretic intensification.

Upon analysis, a total of 4,532 patients in DELIVER (72%) experienced no worsening heart failure event. The analysis showed 789 (13%) patients had outpatient oral diuretic intensification, 86 (1%) required an urgent heart failure visit, 585 (9%) had a heart failure hospitalization, and 271 (4%) died of cardiovascular causes as a first manifestation of worsening heart failure.

Those with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 per 100 person-years) than those without a worsening event (4 per 100 person-years). Rates were similar to those of subsequent death following an urgent heart failure visit (10 per 100 person-years). Notably, those with a heart failure hospitalization as a first presentation of worsening heart failure had the highest rates of subsequent death (35 per 100 person-years).

The addition of outpatient diuretic intensification to the adjudicated DELIVER primary endpoint increased the overall number of patients experiencing an event (1,122 to 1,731). Analyses showed dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio [HR], 0.72; 95% CI, 0.64 - 0.82; P <.001). Dapagliflozin also reduced the need when analyzed as part of an expanded composite endpoint of worsening heart failure (HR, 0.76; 95% CI, 0.69 - 0.84; P <.001).

For more perspective on these findings, watch the full interview with Dr. Chatur. Dr. Chatur reports no relevant disclosures.