Comparison of Long-Term Clinical Implications of Beta-Blockade in Patients With Obstructive Airway Diseases Exposed to Beta-Blockers With Different ß1-Adrenoreceptor Selectivity: An Italian Population-Based Cohort Study.

Rationale: Long-term clinical implications of beta-blockade in obstructive airway diseases remains controversial. We investigated if within the first 5 years of treatment patients with heart failure and obstructive airway diseases using non ß1-adrenoreceptor selective beta-blockers have an increased risk of being hospitalized for all-causes, heart failure, and chronic obstructive pulmonary disease (COPD) when compared to patient using selective beta-blockers. Methods: Carvedilol users were propensity matched 1:1 for co-treatments, age, gender, and year of inclusion in the cohort with metoprolol/bisoprolol/nebivolol users. Cox proportional hazard regression model was used to compare all causes, COPD, and heart failure hospitalization or the beta-blocker discontinuation between cohorts. For statistically significant associations, we computed the rate difference and the attributable risk. Results: Overall, 11,844 patients out of the 51,214 (23.1%) were exposed to carvedilol and 39,370 (76.9%) to metoprolol/bisoprolol/nebivolol. Carvedilol users had a higher hazard for heart failure hospitalization (HR 1.29; 95% Confidence Interval [CI] 1.18-1.40) with 106 (95%CI 76-134; p-value < 0.001) additional cases of heart failure hospitalization per 10000 person-years if compared to metoprolol/bisoprolol/nebivolol users. In all, 26.8% (95%CI 22.5-30.9%; p-value < 0.001) of heart failure hospitalizations in the study population could be attributed to being exposed to carvedilol. Carvedilol users had a higher hazard (HR 1.06; 95%CI 1.02-1.10) of discontinuing the pharmacological treatment with 131 (95%CI 62-201; p-value < 0.001) additional cases of beta-blocker discontinuation per 10000 person-years metoprolol/bisoprolol/nebivolol users. In all, 6.5% (95%CI 3.9-9.0%; p-value < 0.001) of beta-blocker discontinuation could be attributed to being exposed to carvedilol. Conclusion: On long-term follow-up period, carvedilol was associated with a higher risk of heart failure hospitalization and discontinuation if compared to metoprolol/bisoprolol/nebivolol users among patients with heart failure and obstructive airway diseases.

Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system?

BACKGROUND: Statin treatment is often associated with poor adherence, which may be due to the onset of adverse drug reactions (ADRs). We investigated on potential risk factors related to preventable cases of statin-induced ADRs and to the discontinuation of statin therapy. METHODS: We performed a study using the database of Italian spontaneous reporting. The target population for the preventability assessment was all patients with suspected statin-induced ADRs deriving from Campania Region (a territory of Southern Italy) between 2012 and 2017. Additionally, a local sentinel surveillance site involving General Practitioners was selected to countercheck in routine clinical practice the role of ADRs for statin discontinuation. RESULTS: In total, 34 of 655 (5.19%) regional cases were preventable and among detected risk factors 90.0% was related to healthcare professionals' practices and 10.0% to patient behaviour. In 81.4% (533/655) of cases, statin therapy was discontinued due to ADRs, mainly classified as not serious and associated with a positive prognosis. These results were also confirmed in the active sentinel site. CONCLUSIONS: Our findings suggest an inappropriate use of statins among the identified preventable cases and a potential inappropriate statin discontinuation due to ADRs. These factors may be useful for targeting interventions to improve statin adherence.

Hypoglycemia, polycythemia and hyponatremia in a newborn exposed to nebivolol during pregnancy.

Nebivolol is a third-generation beta blocker that exerts selective antagonistic activity on ß1 receptors. It has vasodilating properties that result from direct stimulation of endothelial nitric oxide synthase. Nebivolol is indicated for the treatment of hypertension and heart failure, and is generally well tolerated. In this article, we report a case of an infant who was admitted to the Pediatrics and Neonatology Unit of the Moscati Hospital (Aversa, Italy) about 24 hours after birth. The reason for hospitalization was persistent severe hypoglycemia (blood glucose = 30 mg/dL) and jaundice (total bilirubin = 12.5 mg/dL, indirect bilirubin 11.75 mg/dL). He was born by spontaneous delivery after a normal term pregnancy. Birth weight was 3040 g and the Apgar score was 6-9. The mother reported taking nebivolol 5 mg/day for unspecified tachycardia in the last 4 months of pregnancy. Clinical and instrumental investigations carried out during hospitalization did not reveal any congenital or perinatal abnormalities. After treatment for metabolic and electrolyte imbalance, he was discharged on the 10(th) day of hospitalization, in good clinical condition and with normalization of clinical and laboratory parameters. Currently, there are no specific studies on nebivolol tolerability during pregnancy. Our data suggest that the risk profile of nebivolol during pregnancy is the same as that of other ß-blockers. Therefore, further studies are required to determine the safety of ß-blockers during pregnancy and the risks to the unborn child.