Introduction: The discovery of serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9) has revolutionized pharmacological lipid-lowering treatments. The first PCSK9 antagonists (PCSK9-A), evolocumab and alirocumab, were approved in 2015. Targeting PCSK9 synthesis marked a major advancement in this field, leading to the development of inclisiran, a long-acting siRNA targeting PCSK9 mRNA. However, real-world safety data on this drug are still limited. Therefore, this study aims to provide a real-world safety evaluation of inclisiran, comparing its characteristics to those of PCSK9-As. Methods: A retrospective pharmacovigilance study was conducted using EudraVigilance (EV). Inclisiran-related individual case safety reports (I-ICSRs) from 01/01/2021 to 06/30/2023 were retrieved. ICSRs for evolocumab or alirocumab from 01/01/2015 to 06/30/2023 were collected as a reference group (RG). ADRs were classified using the MedDRA dictionary. Data were evaluated using descriptive and disproportionality analyses. Crude reporting odds ratio (ROR) with 95% confidence intervals (CI) were used as disproportionality measures. Results: Of the 15,236 ICSRs, 3.7% (n = 563) involved inclisiran, with the rest in the RG. Most I-ICSRs involved female patients (51.7%) aged 18 to 64 (52.8%). The most-reported ADRs for inclisiran were “general disorders and administration site conditions” (n = 347) and “investigations” (n = 277). Significant disproportionality was found in I-ICSRs compared to the RG for “Myalgia” (ROR: 2.43; 95% CI: 1.94–3.04), “Low-density lipoprotein increased” (ROR: 11.95; 95% CI: 9.10–15.52), and “Drug ineffective” (ROR: 6.37; 95% CI: 4.64–8.74). Conclusions: The inclisiran safety profile aligns with the existing literature and pre-commercial data. However, further studies are needed to fully understand the observed differences with PCSK9-As.

Chronic venous insufficiency (CVI) represents a risk factor for cardiovascular events. The first-line treatment includes the use of compression stockings and lifestyle changes. Natural products, such as flavonoids, could be used to improve the effects of compression therapy due to their anti-inflammatory and anti-oxidant properties. This study aims to evaluate the effects of a dietary supplement containing baicalin, bromeline and escin in CVI patients. A retrospective cohort study was performed by using the medical records of CVI affected outpatients. Patients treated with the dietary supplement were defined as “users”. A modified Venous Clinical Severity Score (VCSS) was calculated, including pain, inflammation, vessels induration and skin pigmentation. All clinical variables were evaluated at baseline (T0), after 30 (T1) and 90(T2) days in “users” and “non-users”. Out of 62 patients, 30 (48.4%) were “users”. No difference was observed between groups at baseline. A lower VCSS value was recorded in “users” than that observed in “non-users” at T2 (7.0 (4.0–9.0) vs. 9.0 (5.0–10.0); p = 0.025). Vessels’ induration and pain significantly reduced in 53.3% and 43.3% of “users” and in 18.8% and 9.4% of “non-users”. Only “users” (33.3%) showed a reduction of the inflammatory signs as well as a decrease in malleolar circumference, from 29.0 (26.5–30.0) to 27.5 (26.0–28.5) (p < 000.1). A reduction of C-reactive Protein levels was found in “users” compared to “non-users” at T2 (1.0 (0.9–1.2) vs. 1.3 (1.0–1.5); p = 0.006). These findings suggest that implementation of a dietary supplement could improve the clinical outcomes of CVI patients.

Background/Objectives: Ceftazidime/avibactam (CA) and ceftolozane/tazobactam (CT) are WHO Reserve-group antibiotics increasingly used for multidrug-resistant Gram-negative infections. Comparative post-marketing pharmacovigilance data remain limited. Methods: A retrospective pharmacovigilance study was conducted using Individual Case Safety Reports (ICSRs) retrieved from the EudraVigilance database. Reports listing CA or CT as suspected drugs were included. Comparative reporting analyses were performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at System Organ Class (SOC) and Preferred Term (PT) levels. Results: A total of 1414 ICSRs were identified (CA: 967; CT: 447). Serious reports were more frequent for CA than CT (91.0% vs. 78.7%), whereas fatal outcomes were proportionally higher for CT (21.0% vs. 12.8%). At the SOC level, CA showed higher reporting for hepatobiliary disorders (ROR 2.00; 95% CI 1.20–3.35), investigations (ROR 2.67; 95% CI 1.92–3.71), nervous system disorders (ROR 1.51; 95% CI 1.07–2.15), and psychiatric disorders (ROR 3.25; 95% CI 1.37–7.72). At the PT level, CA showed higher reporting for encephalopathy (ROR 4.25; 95% CI 1.28–14.09), blood creatinine increased (ROR 7.37; 95% CI 1.76–30.93), platelet count decreased (ROR 26.9; 95% CI 3.71–195.0), and diarrhoea (ROR 2.83; 95% CI 1.09–7.34). Death was less frequently reported for CA relative to CT (ROR 0.17; 95% CI 0.10–0.29). Conclusions: This EudraVigilance-based analysis identified distinct reporting patterns for CA and CT. CA showed higher reporting for neurological, hepatobiliary, and laboratory-related events, whereas CT reports more frequently involved infection-related contexts. These findings support continued post-marketing surveillance, while clinical monitoring should follow established clinical guidance and product information.