Atrial fibrillation does not reduce dapagliflozin efficacy in HF patients

The presence of atrial fibrillation (AF) at baseline does not appear to modify the benefits of dapagliflozin, compared with placebo, on symptoms and clinical events in patients with heart failure and preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF), according to a study.

“These findings provide further evidence for dapagliflozin as a new treatment option for patients with HFmrEF/HFpEF,” the researchers said.

In this trial, 6,263 HF patients with New York Heart Association functional class II-IV, left ventricular ejection fraction >40 percent, evidence of structural heart disease, and elevated N-terminal pro–B-type natriuretic peptide levels were randomly assigned to treatment with dapagliflozin or placebo.

The researchers assessed the clinical outcomes and effect of dapagliflozin according to AF status. A composite of cardiovascular death or worsening HF was the primary outcome.

A total of 6,261 patients had available data on baseline AF, of whom 43.3 percent had no AF, 18.0 percent had paroxysmal AF, and 38.7 percent had persistent/permanent AF. [J Am Coll Cardiol 2022;80:1705-1717]

Patients with AF, particularly paroxysmal AF, had a higher risk of the primary outcome, and this was driven by an increased rate of HF hospitalization: no AF (4.5 per 100 person-years, 95 percent confidence interval [CI], 4.0‒5.1), paroxysmal AF (7.5 per 100 person-years, 95 percent CI, 6.4‒8.7), and persistent/permanent AF (6.4 per 100 person-years, 95 percent CI, 5.7‒7.1; p<0.001).

Notably, the beneficial effect of dapagliflozin therapy was persistent across the AF types: no AF (hazard ratio [HR], 0.89, 95 percent CI, 0.74‒1.08), paroxysmal AF (HR, 0.75, 95 percent CI, 0.58‒0.97), persistent/permanent AF (HR, 0.79, 95 percent CI, 0.66‒0.95; p=0.49 for interaction).

These effects were consistent for HF hospitalization, cardiovascular death, all-cause mortality, and improvement in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS).

The presence of AF may affect the efficacy of some HFrEF therapies, as seen in trials of beta-blockers, cardiac resynchronization therapy, and omecamtiv mecarbil. This underscores the importance of gauging the efficacy and safety of new therapies in patients with and without AF. [Lancet 2014;384:2235-2243; Circ Heart Fail 2012;5:566-570; Eur Heart J 2022;43:2212-2220]

“In the present report, we demonstrated that the efficacy of dapagliflozin on a range of clinical outcomes was not modified by AF,” the researchers said.

“Specifically, dapagliflozin reduced the risk of the primary composite outcome of worsening HF or cardiovascular death, as well as worsening HF events and HF hospitalizations (both first and recurrent), to a similar extent in patients with and without AF at baseline, without any suggestion of attenuation of benefit regardless of the definition and type of AF,” they added.

In the management of HF patients, reducing symptoms and improving physical function and quality of life are also important. For some patients, improvement in HF-related health status is as valuable as extending life. [Eur Heart J 2021;42:3599-3726; J Am Coll Cardiol 2022;79:17:e263-e421; J Heart Lung Transplant 2001;20:1016-1024]

“Dapagliflozin, compared with placebo, increased the mean KCCQ-TSS after 8 months of treatment, irrespective of AF status,” the researchers noted.

“AF is common in HF, is associated with worse outcomes compared with sinus rhythm, and may modify the effects of therapy,” they said.