Beta-blocker choice and exchangeability in patients with heart failure and chronic obstructive pulmonary disease: an Italian register-based cohort study

Abstract

Clinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease (COPD), metoprolol/bisoprolol/nebivolol should be preferred over carvedilol. However, studies suggest a high proportion of carvedilol usage that remains unexplained. Therefore, we aimed to investigate the predictors of carvedilol choice in patients with heart failure and COPD that were naïve to carvedilol or metoprolol/bisoprolol/nebivolol. Caserta Local Health Unit databases (Italy) were used as data sources. Age, sex, chronic/acute comorbidities, and co-medications were included in a logistic regression model to assess predictors of carvedilol choice. Chronic comorbidities include those defined in the Elixhauser comorbidity index and all hospitalizations within two years prior to the first beta-blocker prescription. Comedications include all redeemed prescriptions within one year prior to the beta-blocker prescription. Kernel density estimations were used to assess the overlap in propensity and preference scores distributions for receiving carvedilol and thereby potential beta-blocker exchangeability. Totally, 10091 patients composed the study population; 2011 were exposed to carvedilol. The overlapping of propensity scores distributions was 57%. Accordingly, the exchangeability was not reached. Atrioventricular block (Odds Ratio, OR 8.20; 95% Confidence Interval, 95% CI 1.30–51.80), cerebrovascular thrombosis (OR 7.06; 95% CI 1.14–43.68), chronic kidney disease (OR 4.32; 95% CI 1.16–16.02), and acute heart failure (OR 1.97; 95% CI 1.28–3.03) hospitalizations were statistically significantly associated with carvedilol choice. Analogously, human insulin (OR 3.00; 95% CI 1.24–7.24), fondaparinux (OR 2.47; 95% CI 1.17–5.21) or strontium ranelate (OR 2.03; 95% CI 1.06–3.90) redeemed prescriptions. In conclusion, this study suggests the absence of beta-blockers exchangeability and a preferential choice of carvedilol in patients with heart failure, COPD and concurrent chronic kidney disease, atrioventricular block, cerebrovascular thrombosis, acute heart failure or redeeming human insulin, fondaparinux or strontium ranelate prescriptions. Therefore, it suggests that choice of prescribing carvedilol over metoprolol/bisoprolol/nebivolol is driven by differences in comorbidities and co-treatments.

The PHARMACOM‐EPI Framework for Integrating Pharmacometric Modelling Into Pharmacoepidemiological Research Using Real‐World Data: Application to Assess Death Associated With Valproate

“…Sessa et al has proposed the use of artificial intelligence for performing data-driven retrieval of predictors and their nonlinear relationship for the outcome using real-world data. 1,[92][93][94][95][96] Such an approach can potentially lead to the identification of risk factors that can further undergo to pharmacological substantiation using available scientific evidence, clinical reasoning, and, in special circumstances, pharmacokinetic and pharmacodynamic considerations. In fact, it is not unusual to have pharmacometric models lacking risk factors for altered pharmacokinetics/pharmacodynamics.…”

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

“…This could be due to preference for carvedilol in patients affected by HF and milder airflow obstruction ( 70 ). However, this choice should be taking into account other comorbidities and co-medications of each patient that physician of internal medicine and geriatric wards had to be considered for the best management of patients affected by HF and concurrent COPD ( 82 ).…”