Continuing Vs. Withholding Home Beta-Blockers at Admission for Suspected Infection: A Target Trial Emulation

OBJECTIVE: Beta-blockers are commonly prescribed for chronic cardiovascular diseases. Despite potential benefits in septic shock, beta-blockers are often held at hospital admission for patients with suspected infection and possible sepsis. We compared the effects of chronic beta-blocker continuation vs. discontinuation on 90-day all-cause mortality among patients admitted from the emergency department with suspected infection. DESIGN: Retrospective cohort study using the target trial emulation framework. We used Cox regression to compare 90-day mortality between treatment groups, with inverse probability of treatment weights to account for baseline differences in sex, race, ethnicity, age, body mass index, presence of a "do not resuscitate" order, comorbidities, and acute illness severity. SETTING: A single large, academic, tertiary care emergency department in the Midwest United States. PATIENTS: Patients 18 years or older on beta-blockers prior to admission hospitalized for suspected infection (defined by orders for blood cultures and broad-spectrum antibiotics). Patients with shock, heart rates less than 40 or greater than 120, or who required an IV beta- or calcium channel blocker at a clinician's discretion were excluded. INTERVENTIONS: Continuation of oral beta-blockers within 48 hours of admission vs. no continuation. MEASUREMENTS AND MAIN RESULTS: Of 4635 eligible patients, 1172 (25.3%) received an oral beta-blocker, whereas 3463 (74.7%) did not receive an oral beta-blocker. Beta-blocker continuation was associated with a reduced risk of all-cause mortality within 90 days of hospital admission (hazard ratio 0.77; 95% CI, 0.61-0.98; p = 0.03) and shorter hospital stay (incidence rate ratio 0.39; 95% CI, 0.38-0.41; p < 0.001). There was no significant association between beta-blocker continuation and in-hospital mortality (odds ratio 0.60; 95% CI, 0.30-1.20; p = 0.15). CONCLUSIONS: Continuation of chronic beta-blockers in a broad population of patients admitted with suspected infection was associated with improved clinical outcomes. Our findings support the need for controlled experimental studies evaluating the role of chronic beta-blocker continuation among patients hospitalized with possible sepsis.