Major cardiovascular events increase in long-term proprotein convertase subtilisin/kexin type 9 inhibitors therapy: the Tuscany cost-effective study.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy.

Methods: During the study period (July 2017 to February 2022) 246 patients (mean age 61 ± 11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study.

Pirfenidone is a cardioprotective drug: Mechanisms of action and preclinical evidence.

Myocardial fibrosis is an endogenous response to different cardiac insults that may become maladaptive over time and contribute to the onset and progression of heart failure (HF). Fibrosis is a direct and indirect target of established HF therapies, namely inhibitors of the renin-angiotensin-aldosterone system, but its resilience to therapy warrants a search for novel, more targeted approaches to myocardial fibrosis. Pirfenidone is a drug approved for idiopathic pulmonary fibrosis, a severe form of idiopathic interstitial pneumonias.

PCSK9 Inhibitors' New Users: Analysis of Prescription Patterns and Patients' Characteristics from an Italian Real-world Study.

Background And Objective: Cardiovascular (CV) diseases represent a major cause of death and severe medical condition worldwide. Different therapeutic options are available to control low-density lipoprotein cholesterol (LDL-C) level in order to prevent CV events. In recent years, two new drugs were approved for patients who are unable to reduce circulating LDL-C with the current therapies: evolocumab and alirocumab (proprotein convertase subtilisin/kexin type nine [PCSK9] inhibitors).

A new potential approach to block HIV-1 replication via protein-protein interaction and strand-transfer inhibition.

Therapeutic treatment of AIDS is recently characterized by a crescent effort towards the identification of multiple ligands able to target different steps of HIV-1 life cycle. Taking into consideration our previously obtained SAR information and combining some important chemical structural features we report herein the synthesis of novel benzyl-indole derivatives as anti-HIV agents. Through this work we identified new dual target small molecules able to inhibit both IN-LEDGF/p75 interaction and the IN strand-transfer step considered as two crucial phases of viral life cycle.

Design and synthesis of N₁-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors.

A series of novel N1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies.