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 ±â€Š11 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. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed. RESULTS: PCSK9i therapy allowed a significant improvement in patients' lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases). CONCLUSION: Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research.

Medication Reconciliation During Hospitalization and in Hospital-Home Interface: An Observational Retrospective Study.

OBJECTIVE: Medication errors are one of the leading causes of patient harms. Medication reconciliation is a fundamental process that to be effective, it should be embraced during each single care transition. Our objectives were to investigate current medication reconciliation practices in the 2 Fondazione Toscana Gabriele Monasterio hospitals and comprehensively assess the quality of medication reconciliation practices between inpatient and outpatient care by analyzing the medication patterns 6 months before admission, during hospitalization, and 9 months after discharge for a selected group of patients with cardiovascular diseases. METHODS: A retrospective observational study was conducted in the Cardiothoracic Department of the Fondazione Toscana Gabriele Monasterio hospitals. Medication history was reviewed for all the patients admitted from and discharged to the community, from January to March 2013. Patients were excluded if they had less than 4 drugs or less than 2 drugs for cardiovascular system in their prescription list at admission or if they died during follow-up. We selected 714 patients, and we obtained the clinical charts and all drug prescriptions collected during patients' hospitalization by the electronic clinical recording system. We also analyzed the list of prescriptions of this sample of patients, from 6 months before admission to 9 months after discharge, extracted from the regional prescription registry. In the resulting sample, prescriptions were analyzed to assess unintentional discrepancies. RESULTS: The study included 298 patients (mean age, 71.2 years), according to the inclusion and exclusion criteria. Among 14,573 prescriptions analyzed, we found 4363 discrepancies (14.6 discrepancies per patient). Among these discrepancies, 1310 were classified as unintentional (4.4 discrepancies per patient). Among unintentional discrepancies, only 63 (4.8%) took place during hospitalization. Although at the hospital-home interface, 33.1% of unintentional discrepancies were detected through the comparison between the patients' declared therapy and the previous medication consumption and 62.1% were identified in the comparison between the prescription at the discharge and the following medication pattern at home. CONCLUSIONS: Medication errors have important implications for patient safety, and their identification is a main target for improving clinical practice. The comparison between the medication patterns acquired through the regional prescription registry before and after hospitalization outlined critical touchpoint in the current medication reconciliation process, calling for the definition of shared medication reconciliation standards between hospitals and primary care services to minimize medication discrepancies and enhance patient safety.

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. Pirfenidone is a small synthetic molecule with high oral bioavailability, exerting an antifibrotic activity, but also anti-oxidant and anti-inflammatory effects. These effects have been attributed to the inhibition of several growth factors (in particular transforming growth factor-ß, but also platelet-derived growth factor and beta fibroblast growth factor), matrix metalloproteinases, and pro-inflammatory mediators (such as interleukin-1ß and tumour necrosis factor-α), and possibly also an improvement of mitochondrial function and modulation of lymphocyte activation. Given the activation of similar profibrotic pathways in lung and heart disease, the crucial role of fibrosis in several cardiac disorders, and the wide spectrum of activity of pirfenidone, this drug has been evaluated with interest as a potential treatment for cardiac disorders. In animal studies, pirfenidone has shown cardioprotective effects across different species and in a variety of models of cardiomyopathy. In the present review we summarize the pharmacological characteristics of pirfenidone and the data from animal studies supporting its cardioprotective effects.

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). This study was aimed to characterise patients who started treatment with PCSK9 inhibitors in the Tuscany region of Italy during the first year of public healthcare service reimbursement and to describe the pattern of PCSK9 inhibitor use in the first 6 months of treatment. METHODS: Patients on PCSK9 inhibitor treatment in Tuscany (3.7 million inhabitants) from 07/2017 to 06/2018 were selected from regional healthcare administrative databases. Concomitant use of lipid-lowering therapies (LLTs), adherence and persistence during the 6 months preceding the first PCSK9 inhibitor dispensing, as well as comorbidities since 1996, were described. In the first 6 months of PCSK9 inhibitor treatment, adherence, persistence and concomitant LLTs were assessed. RESULTS: There were 269 (176 evolocumab, 93 alirocumab) new users of PCSK9 inhibitors. Patients (mean age of 59.1 years) were mainly male (71.0%) in secondary prevention (70.2%) and affected by familial hypercholesterolaemia (53.5%). Sixty-six patients (24.5%) had diabetes mellitus and 12 (4.5%) chronic renal failure. In the 6 months prior to the first PCSK9 inhibitor administration, 61.3% of patients received at least one prescription of ezetimibe or high-intensity statins and 45.7% were persistent to these drugs. During follow-up, 79.9% of patients were adherent to PCSK9 inhibitor and 73.3% were persistent. CONCLUSIONS: During the first year of availability, the rate of prescription of PCSK9 inhibitors appears below expectations. Patients were mainly in secondary prevention and had been slightly persistent to previous LLTs. During follow-up, the PCSK9 inhibitor monotherapy showed high levels of adherence and persistence. This real-world study sets the stage for future longer-term investigations useful to improve our knowledge on the appropriateness, drug access and public healthcare sustainability of PCSK9 inhibitors.