Atrial fibrillation does not reduce the efficacy of dapagliflozin in patients with HF | Latest news for Doctors, Nurses and Pharmacists

Atrial fibrillation does not reduce the efficacy of dapagliflozin in patients with HF |  Latest news for Doctors, Nurses and Pharmacists

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

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

In this trial, 6263 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 B-type natriuretic peptide levels were assigned randomized to treatment with dapagliflozin or placebo.

The investigators evaluated clinical outcomes and the effect of dapagliflozin based on AF status. The primary outcome was a composite of cardiovascular death or worsening HF.

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

Patients with atrial fibrillation, particularly paroxysmal atrial fibrillation, had a higher risk of the primary outcome, and this was due to a higher rate of hospitalization for heart failure: no atrial fibrillation (4.5 per 100 person-years, confidence interval 95 percent [CI]4.0-5.1), paroxysmal AF (7.5 per 100 person-years, 95% CI, 6.4-8.7), and persistent/permanent AF (6.4 per 100 person-years, CI 95%, 5.7-7.1, p<0.001).

In particular, the beneficial effect of dapagliflozin treatment persists in all types of AF: without AF (hazard ratio [HR]0.89, 95% CI, 0.74-1.08), paroxysmal AF (HR, 0.75, 95% CI, 0.58-0.97), persistent/permanent AF (HR, 0, 79, 95% CI, 0.66-0.95, p=0.49 for interaction).

These effects were consistent for hospitalization for heart failure, 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 underlines the importance of measuring 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 demonstrate that the efficacy of dapagliflozin on a variety of clinical outcomes was not modified by AF, regardless of definition or type of AF,” the researchers said.

‚ÄúSpecifically, dapagliflozin reduced the risk of the primary composite outcome of worsening heart failure or cardiovascular death, as well as worsening heart failure events and hospitalization for heart failure (both first and recurrent), to a degree similar in patients with and without AF at baseline, with no suggestion of attenuation of benefit regardless of definition and type of AF,” they added.

In the treatment of patients with HF, reduction of symptoms and improvement of physical function and quality of life are also important. For some patients, improving HF-related health status is as valuable as prolonging 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 mean KSSQ-TSS after 8 months of treatment, regardless of AF status,” the researchers noted.

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

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