Ivabradine and Atrial Fibrillation Incidence: A Nested Matching Study.

BACKGROUND: Ivabradine (IVB) has been utilized for managing hospitalization risk among patients with heart failure (HF). The risk of atrial fibrillation (AF) among IVB patients is poorly understood. OBJECTIVES: The purpose of this study was to assess the risk of developing AF in HF patients receiving IVB. METHODS: A retrospective observational comparative study was performed using a health plan claims database. A new AF diagnosis was compared between adult HF patients receiving IVB vs no-IVB controls (CTRs) over 180-day follow-up period. Eligible IVB subjects were free from AF diagnosis before IVB index date, longer than 6 months. Incidence-density sampling was performed to select matched CTRs based on clinical characteristics and time from the initial HF diagnosis. Cox proportional hazards regression model was used to determine AF risk in patients who did or did not receive IVB. RESULTS: Of the 153 IVB and 4,494,305 CTRs meeting the AF-naive HF status, the analytic cohort of 107 IVB and 321 matched controls were created. The groups were well matched for age: 52.9 ± 11.3 (IVB) vs 53.5 ± 11.8 years, sex: 57% male, heart failure with reduced ejection fraction diagnosis: 66.4%, comorbidities and goal-directed medical therapy: ß-adrenergic blockers 89.7%, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists/sacubitril/valsartan 79.4%, and mineral corticoid antagonists 39.3%. The adjusted HR (95% CI) for developing AF in those receiving IVB was 7.293 (4.985-10.668). CONCLUSIONS: The risk of AF over 180-day period was higher among HF patients who received IVB vs those who did not receive IVB. Further studies are warranted to understand this association, including the impact of unmeasured risk factors and confounding by indication.