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.
Highlights
Beta-blockade is a crucial pharmacological therapy to improve survival and to reduce morbidity in patients with heart failure and concurrent chronic obstructive pulmonary disease[1]
Despite a clinical and pharmacological rationale suggest the use of beta-blockers in heart failure, reluctance to prescribe beta-blockers in patients with the concurrent chronic obstructive pulmonary disease has been observed in multiple clinical settings
In virtue of the potential negative clinical consequences associated with carvedilol choice in patients with heart failure and chronic obstructive pulmonary disease naïve to beta-blockers, understanding key factors that may lead to a preferential choice of such prescriptions is crucial and, in this regard, the evidence is scarce
Summary
Beta-blockade is a crucial pharmacological therapy to improve survival and to reduce morbidity in patients with heart failure and concurrent chronic obstructive pulmonary disease[1]. Carvedilol is a non- beta-1 adrenoceptor selective beta-blockers with an intrinsic sympathomimetic activity, long half-life (7–10 hours) and additional vasodilatation properties mediated by the alpha-1 adrenoceptor blockade. It has anti-oxidant properties, it mitigates calcium overload by modulating ryanodine channels, and it ameliorates insulin sensitivity[6]. The magnitude of the bronchoconstriction is strongly correlated with beta-1 adrenoceptor selectivity[7] For this reason, current clinical guidelines suggest that for patients with heart failure and concurrent chronic obstructive pulmonary disease, metoprolol, bisoprolol or nebivolol should be preferred[8,9]. The investigated predictors included chronic comorbidities defined in the Elixhauser comorbidity index[14], all hospitalizations and redeemed prescriptions within two and one years prior to the first beta-blocker prescription, respectively
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