[ANMCO Position paper: Inclisiran: an innovative therapeutic approach for the clinical management of hypercholesterolemia]. / Position paper ANMCO: Inclisiran: un approccio terapeutico innovativo per la gestione dell'ipercolesterolemia.

Research focused on lipid-lowering treatments has led to the development of new therapeutic options aimed at cardiovascular risk reduction. Gene silencing represents one of the most innovative approaches to reduce low-density lipoprotein cholesterol (LDL-C). Inclisiran is a small interfering RNA that inhibits proprotein convertase subtilisin/kexin type 9 synthesis and promotes LDL-C clearance by enhancing LDL-C receptor expression on hepatocyte cell surface. Several clinical studies have demonstrated inclisiran efficacy in terms of LDL-C reduction (~50%) with a dosage regimen of 300 mg administered twice a year after the first two doses administered at time 0 and after 90 days. Inclisiran use has recently been approved by the European and American drug regulatory agencies as a therapeutic option in addition to the maximum tolerated statin therapy in adults with primary hypercholesterolemia or mixed dyslipidemia who need further LDL-C reduction.

[Cardiovascular prevention in the elderly: limitations and opportunities]. / Prevenzione cardiovascolare negli anziani: limiti e opportunità.

The world's population is ageing; however, the prolonged life expectancy is barely associated with an increase of healthy aging, and an important part of this demographic shift is a rising susceptibility to development and progressive accumulation of multiple chronic illness, challenging healthcare systems. Aging, therefore, represents the major risk factor for multimorbidity, a milestone for progressive loss of resilience and age-related multisystem homeostatic dysregulation. Cardiovascular risk factors, time and comorbidities play a vicious role in the development of heart disease. Among the other comorbidities, age itself is one of the most important risk factors for the development of cardiovascular disease and the prevalence and incidence of cardiovascular disease in the elderly are significantly increased. Elderly subjects, particularly when frail and with comorbidities, however, are scarcely represented in primary and secondary prevention trial aimed to treat hypercholesterolemia, diabetes mellitus and arterial hypertension. In particular, concerns exist about whether treatment should more or less intensive according to tolerability and risk of interactions; as well as there is uncertainty about therapeutic targets at different ages.This article reviews the relationship between ageing and cardiovascular disease, focusing on several issues regarding cardiovascular prevention in the elderly.

[ANMCO statement: Arterial and venous thromboembolism: what implications for clinical practice?] / Statement ANMCO: Tromboembolismo arterioso e venoso: quali implicazioni per la pratica clinica?

Acute myocardial infarction, stroke, peripheral arterial disease and pulmonary embolism share thrombosis as a common mechanism. Some well-known risk factors for arterial thromboembolism are recognized as "weak risk factors" of venous one, too. Arterial and venous thrombosis share also some pathophysiological mechanisms, including inflammation, endothelial damage, and hypercoagulability. It is likely, thus, that any disease related to arterial and venous thrombosis belong to the same "pan-vascular syndrome", that constitutes itself a chronic, recurrent inflammatory disease. According to the available data, there are elements for implementing an omni-comprehensive cardiovascular evaluation after an episode of venous thromboembolism, requiring the investigations, in addition to the known unrecognized prothrombotic conditions, also of indirect signs and risk factors for a possible arterial thromboembolic event. Large, prospective studies are needed to establish the more appropriate therapeutic strategies in this context.The aim of the present statement is to make aware all the physicians involved in the management of arterial and venous diseases and to provide some tools for evaluating the implications of related major risk factors. Thus, it could be possible to lay the foundation for a reduction of total cardiovascular risk, in terms of primary and secondary prevention of arterial and venous thromboembolism.

Direct oral anticoagulants in patients undergoing cardioversion: insight from randomized clinical trials.

Anticoagulation, reducing the risk of thromboembolic events in patients undergoing cardioversion, is a cornerstone of peri-cardioversion management in patients with atrial fibrillation. We aimed to analyse published data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients undergoing cardioversion. We performed a systematic review of randomized prospective clinical trials (RCTs) comparing DOACs with warfarin and reporting data on post-cardioversion outcomes of interest. Outcomes of interest were stroke, systemic thromboembolic events and major bleeding. We reviewed a total of six RCTs including 3900 cardioversions performed using a DOAC for thromboembolic prophylaxis. These studies reported a low incidence overall of adverse outcomes associated with the use of DOACs (around 1% in all studies, except the ROCKET post-hoc study which included ablation procedures). The incidence rate of adverse events during DOAC treatment was found to be very similar to that observed with warfarin anticoagulation. In RCTs DOAC treatment in patients undergoing cardioversion appears to be effective and safe. However, because evidence in this clinical setting is still weak, observational reports could be useful in providing further data about peri-procedural outcomes.

Early invasive versus early conservative strategy in non-ST-elevation acute coronary syndrome: An outcome research study.

BACKGROUND: An early invasive strategy (EIS) has been shown to yield a better clinical outcome than an early conservative strategy (ECS) in patients with non-ST-elevation acute coronary syndromes (NSTEACSs), particularly in those at higher risk according to the GRACE risk score. However, findings of the clinical trials have not been confirmed in registries. OBJECTIVE: To investigate the outcome of patients with NSTEACS treated according to an EIS or a ECS in a real-world all-comers outcome research study. METHODS: The primary hypothesis of the study was the non-inferiority of an ECS in comparison with an EIS as to a combined primary end-point of death, non-fatal myocardial infarction and hospital readmission for acute coronary syndromes at one year. Participating centres were divided into two groups: those with a pre-specified routine EIS and those with a pre-specified routine ECS. Two statistical analyses were performed: a) an 'intention to treat' analysis: all patients were considered to be treated according to the pre-specified routine strategy of that centre; b) a 'per protocol' analysis: patients were analysed according to the actual treatment applied. Cox model including propensity score correction was applied for all analyses. RESULTS: The intention to treat analysis showed an equivalence between EIS and ECS (11.4% vs. 11.1%) with regard to the primary end-point incidence at one year. In the three subgroups of patients according to the GRACE risk score (⩽ 108, 109-140, > 140), EIS and ECS confirmed their equivalence (5.3% vs. 3.9%, 8.4% vs. 7.6%, and 20.3% vs. 20.9%, respectively). When the per protocol analysis was applied, a reduction of the primary end-point at one year with EIS vs. ECS was demonstrated (6.2% vs. 15.3%, p=0.021); analysis of the subgroups according to the GRACE risk score numerically confirmed these data (3.1% vs. 6.5%, 5.1% vs. 10.0%, and 10.8% vs. 24.5%, respectively). CONCLUSIONS: In a real-life registry of all-comers NSTEACS patients, ECS was non-inferior to EIS; however, when EIS was applied according to clinical judgement, a reduction of clinical events at one year was demonstrated.

Clinical Implications of Switching Lipid Lowering Treatment from Rosuvastatin to Other Agents in Primary Care.

INTRODUCTION: Switching from any statin to another non-equipotent lipid lowering treatment (LLT) may cause a low-density lipoprotein cholesterol increase and has been associated with a higher probability of negative cardiovascular outcomes. The aim of the study was to assess the impact of switching from rosuvastatin to any other LLT on clinical outcomes in primary care. METHODS: This was a retrospective analysis based on data from IMS Health Longitudinal Patient Database, which is a general practice database including information of more than 1.0 million patients representative of the Italian population by age, and medical conditions. Patients that started on rosuvastatin (10-40 mg/day) between January 2011 and December 2013 were considered. The date of the first prescription was defined as the index date (ID). The observation period lasted from the ID to September 2015 or until LLT discontinuation, or the occurrence of an acute myocardial infarction (AMI), or death. RESULTS: The primary end point of the study was the occurrence of an AMI during the observation period. The final study population included 10,368 patients. During the observation period, 2452 (23.6%) patients were switched from rosuvastatin to another LLT. The majority of patients (55.6%) were switched to atorvastatin, followed by simvastatin (24.9%), simvastatin/ezetimibe combination (10.0%) and other statins (9.5%). Female gender (HR, hazard ratio, 1.10, 95% CI, confidence interval, 1.02-1.19, p = 0.04) and the presence of chronic kidney disease (HR 1.47, 95% CI 1.16-1.86, p = 0.05) were associated with a higher probability of switch. During the observation period, 113 patients experienced an AMI (incidence of 6.7 AMI/1000 patient-years). Multivariate analysis with Cox proportional hazards method, including switching as a time-dependent covariate, demonstrated that changing from rosuvastatin to another LLT was an independent predictor of AMI (HR 2.2, 95% CI 1.4-3.5, p = 0.001). CONCLUSION: We conclude that switching from rosuvastatin to another non-equipotent LLT may impart an increased risk of AMI and should be avoided. FUNDING: AstraZeneca SpA.

Effect of smoking relapse on outcome after acute coronary syndromes.

The aim of the present study was to evaluate the smoking relapse rate among smokers who had become abstinent during admission for acute coronary syndromes. The association between smoking relapse and mortality was also analyzed. A cohort of 1,294 consecutive active smokers who had interrupted smoking after admission for acute coronary syndromes (1,018 men and 276 women, mean age 59.7 ± 12.3 years) was followed up for 12 months after the index admission. All patients received a brief in-hospital smoking cessation intervention consisting of repeated counseling sessions. During follow-up, 813 patients (62.8%) resumed regular smoking (median interval to relapse 19 days, interquartile range 9 to 76). Increasing age (hazard ratio [HR] 1.034 per year, 95% confidence interval [CI] 1.028 to 1.039, p = 0.001) and female gender (HR 1.23, 95% CI 1.09 to 1.42, p = 0.03) were independent predictors of smoking relapse. Patients enrolled in a cardiac rehabilitation program (HR 0.74, 95% CI 0.51 to 0.91, p = 0.02) and those with diabetes (HR 0.79, 95% CI 0.68 to 0.94, p = 0.03) were more likely to remain abstinent. During follow-up, 97 patients died (1-year probability of death 0.075, 95% CI 0.061 to 0.090). Multivariate analysis with the Cox proportional hazard regression method, including smoking relapse as a time-dependent covariate, demonstrated that, after adjustment for patient demographics, the clinical history features and variables related to the index event, the resumption of smoking was an independent predictor of total mortality (HR 3.1, 95% CI 1.3 to 5.7, p = 0.004). In conclusion, smoking relapse after acute coronary syndromes is associated with increased mortality, and counseling interventions should be integrated into the postdischarge support to reduce the negative effects of smoking resumption.

[Atrioventricular asynchrony and pacing]. / Asincronie atrioventricolari e pacing.

Atrioventricular dissociation and atrioventricular block are the most common types of atrioventricular asynchrony. Less frequently, atrioventricular asynchrony may occur in the pacemaker syndrome or during sequential pacing with programmed asynchronous atrioventricular delay. A rare type of atrioventricular asynchrony that has relevant hemodynamic effects is observed in first-degree atrioventricular block when associated with mitral stenosis or other conditions characterized by an obstruction of the left atrial outflow. Atrioventricular asynchrony can be defined as systolic when both the atrium and ventricle are contracting simultaneously (pacemaker syndrome, sequential pacing with programmed asynchronous atrioventricular interval), or systo-diastolic when atrial systole occurs at the onset of ventricular diastole as observed in patients with very long PR interval. All described asynchronies can be eliminated by sequential pacing with programmed synchronous atrioventricular delay.