Objective: Cardiovascular disease often coexists with chronic liver disease (CLD). Therefore, beta-blockers are commonly used in patients with underlying metabolic dysfunction-associated steatotic liver disease (MASLD) or liver cirrhosis, which could potentially exacerbate their safety risks. Our population-based cohort study aimed to quantify the excess of beta-blocker related safety risks among patients with MASLD or liver cirrhosis, as compared to patients without CLD. Design and method: We utilized data from a large German claims database (9 million individuals). We included adults initiating an oral beta-blocker between 2017 and 2024 and further classified them according to baseline liver disease status (no CLD, MASLD, cirrhosis). Patients diagnosed with hepatocellular carcinoma or undergoing liver transplantation in the year prior were excluded. Outcomes were (i) a composite cardiovascular endpoint including bradycardia, atrioventricular blockade, hypotension, syncope, fractures, and dislocations and (ii) hyperkalemia, all defined using hospitalization diagnoses. Cox models estimated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the outcomes associated with beta-blocker use among patients with MASLD or cirrhosis, compared to beta-blocker use among non-CLD patients. Propensity score-based inverse-probability-of-treatment weighting controlled for confounding. Secondary analyses stratified by age and sex. Results: The study cohort included overall 738,392 patients who initiated beta-blockers (mean age 59 years; 51% female). At baseline, 675,789 patients did not have CLD, 52,678 were diagnosed with MASLD, and 9,925 were diagnosed with cirrhosis. As compared to beta-blocker use among non-CLD patients, beta-blocker use among patients with MASLD was associated with an increased risk of the cardiovascular endpoint (HR, 1.07; 95% CI, 1.01-1.13) but not hyperkalemia (HR, 1.00; 95% CI, 0.91-1.11), while beta-blocker use among patients with cirrhosis was associated with increased risks of the cardiovascular endpoint (HR, 1.54; 95% CI, 1.41-1.68) and hyperkalemia (HR, 2.56; 95% CI, 2.26-2.89). The increased risk of hyperkalemia was driven by patients <65 years. Conclusions: Our large population-based cohort study showed that among users of beta-blockers, MASLD was associated with a modestly increased cardiovascular risk, while cirrhosis was associated with strongly increased cardiovascular and hyperkalemia risks, as compared to non-CLD. These elevated safety risks should be considered during treatment with beta-blockers.
Josuweit et al. (Fri,) studied this question.