Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation: Findings From the ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) Registry

Abstract

BackgroundMineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes.Methods and ResultsIn order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity‐matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow‐up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow‐up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88–1.58; P=0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02–1.23; P=0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers.ConclusionsIn community‐based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF.

Incidence of Atrial Fibrillation and Mineralocorticoid Receptor Activity in Patients With Medically and Surgically Treated Primary Aldosteronism

“…The current study provides clinically relevant evidence from an extreme state of hyperaldosteronism that using MR antagonists to adequately block the MR, or removal of the unilateral source of aldosterone excess via surgical adrenalectomy, may mitigate the excess risk for atrial fibrillation attributed to pathologic MR activation. These findings are in agreement with recent studies in essential hypertension and heart failure, which suggest that blockade of the MR may be a potential target for preventing or delaying the incidence of atrial fibrillation and stroke. Our findings may also help contextualize prior studies in cohorts with PA that did not include an evaluation of physiological biomarkers of MR blockade and observed that lifelong MR antagonist therapy did not lower the risk for atrial fibrillation, whereas surgical adrenalectomy did …”

Heart failure patients with atrial fibrillation benefit from remote patient management: insights from the TIM‐HF2 trial

“…However, up‐titration of guideline‐recommended treatments or dosing of diuretics during the TIM‐HF2 trial were similar in the AF and SR patients, both groups in the RPM trial arm received a similar number of cardiac medication changes by a TMC physician during the trial. Previous subgroup analyses of AF patients showed differences between groups with regard to RAAS inhibitors, neprilysin inhibition, beta blocker therapy, mineraloreceptor antagonists, and SGLT2‐inhibition 25–27 . Differences in the pharmacotherapy therefore appear unlikely to explain the profound benefit for AF patients randomized to RPM.…”

“…Previous subgroup analyses of AF patients showed differences between groups with regard to RAAS inhibitors, neprilysin inhibition, beta blocker therapy, mineraloreceptor antagonists, and SGLT2inhibition. [25][26][27] Differences in the pharmacotherapy therefore appear unlikely to explain the profound benefit for AF patients randomized to RPM.…”

Posttranslational Modifications of the Mineralocorticoid Receptor and Cardiovascular Aging

“…Overall, a reduction in mortality and morbidity was registered. Additional clinical benefits of MR antagonists were reported in patients with left ventricular hypertrophy and hypertension (Pitt et al, 2003) and in patients with atrial fibrillation (Dabrowski et al, 2010;Fudim et al, 2018). For patients with heart failure with preserved ejection fraction, the picture is less clear with no significant reduction in the primary composite outcome of death due to cardiovascular causes or hospitalization (Pitt et al, 2014).…”