CHICAGO, IL—The use sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was more effective than valsartan at preventing the recurrence of atrial arrhythmias following catheter ablation for atrial fibrillation (AF), according to results of the SUPERIOR trial.
The incidence of any ECG-documented AF, atrial flutter, or atrial tachycardia between 3 months and 1 year after catheter ablation was significantly lower with among the ARNI-treated patients than in those treated with the angiotensin receptor blocker (ARB), reported investigators today at the American Heart Association 2026 Scientific Sessions.
“The results suggest that the choice of hypertension medication after atrial fibrillation ablation may influence the likelihood of recurrence,” said lead investigator Wei Zhang, MD (Shanghai Institute of Hypertension, China), during a morning press conference. “What remains uncertain is whether the benefit lasts beyond 1 year and whether similar results may occur in a broader patient population.”
The study was open label and relatively small, with just 320 patients (mean age 68 years, 58.8% men) randomized at 3 hospitals in China. All patients had a diagnosis of paroxysmal or persistent AF.
We tend to ablate and not target these important risk factors that alter the long-term prognosis of these patients.
Ratika Parkash
Ratika Parkash, MD (Dalhousie University/Queen Elizabeth II Health Sciences Center, Halifax, Canada), said there is mechanistic data to support the SUPERIOR findings. Neprilysin is an enzyme that degrades natriuretic peptides, and sacubitril/valsartan, in blocking neprilysin, prevents the breakdown. This leads to several key physiologic effects, including a reduction in fibrosis, oxidative stress, and atrial stretch, as well as a shortening of the atrial effective refractory period.
“So, there may be some benefit for this particular molecule to modify the substrate,” she said. Once the atrium starts to remodel, with myocardial scarring and inflammation, the tissue may be too damaged for pharmacotherapy to the prevent negative processes. “We really need something to target the atrial tissue before it reaches the point of no return and to reverse progression,” said Parkash.
Open-Label Design
The SUPERIOR investigators randomized 161 patients to sacubitril/valsartan 100 mg once daily and 159 patients to valsartan 80 mg once daily, with blood pressure-guided titration up to 200 mg and 160 mg once daily, respectively less. The titration algorithm used a clinic blood pressure threshold of 130/80 mmHg. Scheduled 12-lead and 24-hour Holter monitoring took place at 1, 3, 6, and 12 months and patients were also encouraged to obtain handheld single-lead ECG recordings at least twice weekly (or whenever symptoms occurred).
Two-thirds of patients had paroxysmal AF and the mean duration since AF diagnosis was 3.0 years. Mean BMI was 25.1 kg/m2. In all, 78% were treated with a prior antihypertensive medication, with 55.3% treated with an ACE inhibitor/ARB, 43.8% with beta blockers, 45.4% with calcium-channel blockers, and 6.6% with an ARNI.
After the 3-month blanking period, 29 of 161 patients during 138.5 person-years of follow-up in the ARNI group had a documented atrial tachyarrhythmia lasting at least 30 seconds. Comparatively, 45 of 159 patients during 124.6 person-years of follow-up in the valsartan arm had a documented event. This translated into an incidence rate of 20.9 and 36.1 events per 100 person-years (P = 0.03) in the ARNI and valsartan groups, respectively.
There was a trend toward less AF recurrence with sacubitril/valsartan in the first 90 days, but the difference wasn’t statistically significant. There was no difference in clinic or 24-hour blood pressure between the two treatment arms.
Study Needs Confirmation
To Cardiology Now News, Zhang said they selected an open-label design because the trial included two active drug therapies. He acknowledged this as a limitation, but the ECG assessment of atrial tachyarrhythmia recurrence “compensates for the open-label design.” In terms of clinical implications, Zhang said use of an ARNI after successful catheter ablation isn’t for everybody, but sacubitril/valsartan could be an option, particularly in older patients with hypertension.
For Parkash, the results are exciting, but she noted the study included patients with predominantly paroxysmal AF and with few comorbidities. This is suggestive of a patient group early in the disease course. She also noted there was an imbalance in the prior use of antihypertensive therapy, with more patients in the ARNI group treated with ACE inhibitors/ARBs. This upstream therapy may have contributed to the positive result.
With no difference in blood pressure between treatment groups, Parkash said the results suggest the benefit might be a class effect, but the study needs to be replicated in a blinded, multicenter trial with continuous AF monitoring to better understand the effect of sacubitril/valsartan on AF burden.
In the meantime, “it’s absolutely critical that hypertension, sleep apnea, obesity, diabetes, and alcohol use, they all need to be treated,” Parkash told Cardiology Now News. “They are part and parcel of the cardiometabolic profile of patients with atrial fibrillation…That often is not on the radar. We tend to ablate and not target these important risk factors that alter the long-term prognosis of these patients.
Source:
Zhang W, on behalf of the SUPERIOR investigators. Sacubitril/valsartan versus valsartan after catheter ablation for atrial fibrillation in older patients with hypertension: the SUPERIOR randomized trial. Presented at American Heart Association Scientific Sessions, November 8, 2026.
Disclosures:
Zhang reports no conflicts of interest.
Parkash reports grants from Medtronic and Abbott Laboratories.