The FUNCTION Study: A Randomized Controlled Trial on the Efficacy of Sacubitril/Valsartan on the Success Rate of Catheter Ablation for Nonparoxysmal Atrial Fibrillation.

PURPOSE: The efficacy of radiofrequency catheter ablation (RFCA) alone for nonparoxysmal atrial fibrillation (NPAF) is unsatisfactory. This study investigated the effect of sacubitril/valsartan, a type of angiotensin receptor neprilysin inhibitor (ARNI), on NPAF patients with hypertension who underwent RFCA and analysed the possible influencing factors.

METHODS

In this prospective, randomized clinical trial, 240 NPAF patients were randomly divided into a control group (n = 121) and an ARNI group (n = 119). The primary outcome was freedom from atrial fibrillation (AF) and atrial tachycardia/atrial flutter (AT/AFL) for ≥ 30 s without antiarrhythmic medications at 15 months after the 3-month blanking period. The secondary outcomes included recurrence types, blood pressure, echocardiographic parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.

RESULTS

At 15 months, a higher maintenance rate of sinus rhythm was achieved in the ARNI group compared to the control group (79.8% vs. 69.4%, hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.36-0.98; P = 0.04). Moreover, a smaller left atrial diameter (adjusted mean difference -1.9 mm [95% CI -3.2 to -0.5], P = 0.02) and lower NT-proBNP level (adjusted median difference -34 pg/ml [95% CI -62 to -6], P = 0.03) were observed in the ARNI group than in the control group at 15 months. Among the patients who recurred, a lower incidence of AF (50.0% vs. 62.2%, P = 0.01) was found in the ARNI group, but presented a significantly higher incidence of AT/AFL. In the subgroup analysis, compared with those in the control group, more patients in the ARNI group achieved success in patients with EF < 50% (93.6% vs. 61.1%, P = 0.01) or low-voltage areas (LVAs) (80.0% vs. 61.3%, P = 0.02). Multivariate Cox regression analysis revealed that ARNI was an independent protective factor against AF or AT/AFL recurrence in patients with EF < 50% or LVAs at 15 months.

CONCLUSION

ARNI is effective in NPAF patients with hypertension after RFCA, especially those with EF < 50% or LVAs, which can significantly improve their prognosis.