Secondary prevention and follow-up of patients with ACS and not-at-target LDL: An Italian real-world retro-prospective analysis by the inertia group.

Background: In patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. Objective: Report a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. Methods: Retrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. Results: Data from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C <55 mg/dL according to ESC 2019 guidelines. Fifty percent of patients achieved the <55 mg/dL target for LDL-C after a mean of 120 days from the ACS event. Conclusions: Our analysis, though numerically and methodologically limited, suggests that management of cholesterolaemia and achievement of LDL-C targets are largely suboptimal and need significant improvement to comply with the lipid-lowering guidelines for very high CV risk patients. Earlier high intensity statin combination therapy should be encouraged in patients with high residual risk.

Persistence on apixaban in atrial fibrillation patients: a retrospective multicentre study.

AIMS: Real-world data on treatment persistence, safety and effectiveness of non-Vitamin K antagonist oral anticoagulants (NOACs) play an important role in the assessment of risks and benefits of these drugs. Our aim was to evaluate persistence on treatment, incidence of major bleeding and incidence of a composite endpoint of major events, including all-cause death, myocardial infarction, stroke and systemic thromboembolism, during treatment with apixaban in a cohort of patients with nonvalvular atrial fibrillation (NVAF). METHODS: In this multicentre retrospective observational study, we retrieved data from medical records of five Italian hospitals on patients with a diagnosis of NVAF who initiated apixaban between 1 January 2014 and 31 March 2016 and had a first subsequent visit at the same hospital. RESULTS: We studied 766 patients with mean age of 74.2 (standard deviation 11.1) years and median CHADS2 and CHA2DS2VASc scores of 2.0 and 4.0, respectively. Over a median follow-up period of 339 days, persistence on treatment was 83.5% [95% confidence interval (95% CI) 75.5-89.1%]. The rate of major bleeding (per 100 person-years) was 1.15 (95% CI 0.39-1.90 per 100 person-years), while the cumulative incidence was 4.4% (95% CI 1.6-12.0). The rate of major events was 1.97 (95% CI 1.08-2.86) per 100 patient-years, with a cumulative incidence over the entire follow-up period of 7.7% (95% CI 4.6-12.8). CONCLUSION: In real-life conditions, NVAF patients treated with apixaban show rates of treatment discontinuation and major bleedings, which are comparable to those found in the ARISTOTLE pivotal study, thus supporting its external validity.

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy.

BACKGROUND: Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. DESIGN: Case-control study. METHODS: Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. RESULTS: 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. CONCLUSION: Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: the impact of late referral.

BACKGROUND: Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS: Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS: Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS: Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.

Venous endotelin-1 (ET-1) and brain natriuretic peptide (BNP) plasma levels during 6-month bosentan treatment for pulmonary arterial hypertension.

OBJECTIVE: Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. SETTING AND PATIENTS: Twenty-five patients with PAH (idiopathic n=16, CTD n=9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1<18.7 pg/ml, Gr.2>18.7 pg/ml). RESULTS: Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435+/-85) m to 467+/-77 m, p>0.001) and an improvement in WHO class (from 2.4+/-0.5 to 2+/-0.6 p>0.01), with a significant decrease in BNP (from 87+/-33 pg/ml to 67+/-41 pg/ml, p=0.006) and a trend towards lower ET-1 plasma levels (from 17.7+/-5 pg/ml to 16+/-6 pg/ml, p=ns). Improvement in effort tolerance (Delta distance) was not correlated to modification in ET-1 (DeltaET-1) and BNP (DeltaBNP) plasma levels, while we found a significant correlation between DeltaET-1 and DeltaBNP (r=0.63, p=0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41+/-10 years vs Gr.2: 50+/-9 years, p=0.04), had less effort capacity (6MWT distance, Gr.1: 469+/-76 m, vs Gr.2: 398+/-82 m, p=0.03), and showed a trend towards higher BNP values (Gr.1: 82+/-41 pg/ml vs Gr.2: 92+/-23 pg/ml, p=0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: +32+/-24 m, Gr.2: +32+/-21 m p=0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: -0.5+/-0.5, Gr.2: -0.3+/-0.4 p=0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: -6+/-41 pg/ml, Gr.2: -34+/-19 pg/ml p=0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2+/-4.6 pg/ml, Gr.2: -3.8+/-6.6 pg/ml p=0.09). CONCLUSIONS: Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy.