Dapagliflozin Benefits Women and Men With Heart Failure

Women and men with heart failure with reduced ejection fraction (HFrEF)—all participants in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial—similarly benefited from the addition of dapagliflozin to their treatment regimens.

Diabetes status did not affect these results, according to the findings published recently in JAMA Cardiology.

Women with HF generally have a greater disease burden and they have been shown to benefit less from treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors, of which dapagliflozin is one. However, this class has also proven itself in recent years as “a valuable treatment for HFrEF, and it is clearly important to examine the effects of this therapy in women as well as men with HFrEF,” the authors noted.

The 4744 patients included in this analysis (23.4% women), with a primary outcome of worsening HF (eg, hospitalization or urgent visit with intravenous therapy) or cardiovascular death, had New York Heart Association functional class II through IV disease and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. They were randomized to an addition of either 10-mg one-daily dapagliflozin or placebo.

Dapagliflozin was shown to similarly lessen the risk of worsening HF events or CV death in men and women:

• Men gained a 27% lesser risk (HR, 0.73; 95% CI, 0.63-0.85)
• Women gained a 21% lesser risk (HR, 0.79; 95% CI, 0.59-1.06; P _interaction = .67)

The SGLT2 inhibitor also resulted in there being more patients with meaningful symptom improvement and fewer with worsening symptoms vs placebo, respectively, as measured by the Kansas City Cardiomyopathy Questionnaire total symptom score:

• Total symptom score improvement of > 5 points:
  • Women: 57% vs 54%
  • Men 59% vs 50% (P_interaction = .14)
• Symptom score decrease of > 5 points:
  • Women: 27% vs 31%
  • Men: 25% vs 34% (P_interaction = .15)

Treatment discontinuation and the rate of serious adverse events, too, were consistent among the men (mean [SD] age, 65.9 [10.9] years) and women (mean age, 67.6 [10.7] years).

The women in the study tended to be older and Black. They also had a lesser likelihood of atrial fibrillation, chronic obstructive pulmonary disease, and anemia, but a greater chance of having higher systolic blood pressure, heart rate, and baseline NT-proBNP.

Analyses also found:

• 28% lower risk of worsening HF or CV death in women (adjusted HR, 0.72; 95% CI, 0.61-0.85) vs men
• 20% lower risk of HF hospitalization or CV death in women (HR, 0.80; 95% CI, 0.59-1.08)
• 27% lower risk of HF hospitalization or CV death in men (HR, 0.73; 95% CI, 0.63-0.85)
• 31% lower risk of hospitalizations in men (HR, 0.69; 95% CI, 0.57-0.84)
• 27% lower risk of hospitalizations in women (HR, 0.73; 95%, 0.51-1.06)
• 16% lower risk of CV death in men (HR, 0.84; 95% CI, 0.69-1.02)
• 24% lower risk of CV death in women (HR, 0.76; 95% CI, 0.49-1.16)

In addition, systolic blood pressure similarly decreased in both patient groups. At the 4-month mark, this amounted to –1.69 mm Hg (95% CI, –3.37 to –0.02) for the women and –1.88 mm Hg (95% CI, –2.80 to –0.96) for the men.

“Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction,” the authors concluded. “Collectively, these data provide further support for dapagliflozin as a new treatment option for HFrEF.”

Importantly, the authors highlight that their finding should offer reassurance that dapagliflozin is tolerable and safe for use among patients with HFrEF, women and men.

Reference

Butt JH, Docherty KF, Petrie MC, et al. Efficacy and safety of dapagliflozin in men and women with heart failure with reduced ejection fraction: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in heart failure trial. JAMA Cardiol. Published online March 31, 2021. doi:10.1001/jamacardio.2021.0379