History of betablocker treatment breaks and risk of ventricular tachyarrhythmias among patients with heart failure and implantable cardioverter defibrillator: a nationwide cohort study

Background Beta-blockers have in randomized clinical trials been shown to reduce the risk of life-threatening arrhythmias and sudden cardiac death (SCD) in patients with heart failure (HF), and treatment is a class 1A recommendation in current guidelines. Thus, beta-blocker treatment breaks (i.e. planned break, beta-blocker related side-effects, or poor adherence) may increase risk of life-threatening arrhythmias and SCD. Whether patients with HF and a history of beta-blocker treatment breaks before implantable cardioverter defibrillator (ICD) is associated with increased risk of device related therapy and mortality is largely unknown. Aims In patients with HF and an ICD alone or combined with cardiac resynchronization therapy (CRT-D), we examined the association between a history of a beta-blocker treatment breaks prior to device implantation and the risk of appropriate and inappropriate device related therapy (i.e., anti-tachycardia pacing [ATP] or DC shock [DC]), and all-cause mortality. Methods Using the Danish Pacemaker and ICD Registry, we identified all patients with HF receiving a first-time ICD (2000–2018). Beta-blocker treatment breaks >60 consecutive days up to 3 years prior to device implantation were identified using the National Prescription Registry. Patients were able to switch between beta-blockers and were required to be in treatment at the time of implantation. We used multivariable Cox regressions to compare the 1-year risks of device-related therapy and all-cause mortality between patients with and without a history of a beta-blocker treatment break. Results We identified 9,239 patients with HF and an ICD (82.6% male; median age 67 years). A total of 82.5% had ischemic heart disease, 33.9% atrial fibrillation, and 33.1% of ICDs were secondary prophylaxis. During one-year follow-up, 5.7% of all patients died and appropriate DC and appropriate ATP was identified for 3.9% and 6.7% of patients, respectively. Overall, 14.6% of all HF patients had one or more beta-blocker treatment break >60 days. Compared with HF patients with no history of treatment breaks, a history of treatment breaks >60 days were associated with increased risk of appropriate DC (hazard ratio (HR)=1.33; 95% confidence interval [CI], 1.02–1.73) and appropriate ATP (HR 1.30; CI, 1.06–1.59), but also inappropriate DC and ATP therapy (Figure 1). There was no difference between groups with respect to all-cause mortality (HR=0.96; CI: 0.76–1.22). Treatment breaks of >30 or >90 days were also evaluated and yielded similar results as the main analysis. Conclusion Patients with heart failure who had a history of treatment breaks with beta-blockers prior to ICD implantation was associated with a higher 1-year risk of appropriate and inappropriate shocks and anti-tachycardia pacing, but not all-cause mortality.