Publications

Abstract Aims OMERO is a prospective study, aimed to assess the long-term effectiveness, tolerability, and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i), in the real life in Italy. The study is planned to include 800 patients, from 40 Italian sites, treated with alirocumab on top of standard lipid lowering therapy. Methods and results This analysis concerns 699 (out of 800) patients with all data available: 65.5% male; mean age 60.6 ± 11.09 years; 29.6% with HeFH in primary prevention; 70.4% in secondary prevention (with/without HeFH). Before ALI administration, 461 patients (66%) were treated with statins while 231 (33%) reported statin intolerance, that resulted in the statin discontinuation. Mean baseline LDL-C was 161.5 ± (53.07) mg/dl. Based on clinical judgement, ALI was initially prescribed at 75 mg Q2W dosing regimen in 60.80% of participants, whereas the remainder received 150 mg Q2W. At V1 57 patients (89.06%) switch from 75 mg Q2W to 150 mg Q2W and 7 patients (10.94%) from 150 mg Q2W to 75 mg Q2W. LDL-C level reduction from baseline (before ALI administration) to 6 months from the study enrolment (V1), was −45% (V1: mean LDL-C was 73.5 ± 45.70 mg/dl). LDL-C levels at V1 by participant category are shown in Figure 1. The rate of patients with at least one adverse event was 25.6% (of which SAE 7.4%); the rate of patients with at least one related adverse reaction to treatment was 3.8% none of them were serious. Conclusions OMERO confirmed in clinical practice the results observed in trials: a significant reduction of LDL-C was observed with ALI 75/150 mg Q2W in participants at high CV risk with or without HeFH. ALI was generally well tolerated.

Abstract Background The accuracy of the 2014 ESC model to predict 30-day mortality in hemodynamically stable patients with acute pulmonary embolism (PE) is relatively limited. Purpose The aims of this study in hemodynamically stable patients with acute PE were i) to evaluate the prognostic value of a novel respiratory index (RI) (oxygen saturation in air to respiratory rate ratio) and ii) to assess the accuracy of the RI-model (simplified Pulmonary Embolism Severity Index [sPESI] + RI), both in predicting 30-day mortality. Methods A collaborative database of hemodynamically stable patients with PE was divided into two cohorts (derivation and validation) with equal numbers of patients, based on a temporal criterion. Study outcome was 30-day all-cause-death. Discrimination and calibration were assessed in the derivation and validation cohorts by the c-statistics and by the Hosmer-Lemeshow test, respectively. Results 30-day all-cause-death occurred in 7.5% of the 319 patients in the derivation cohort (mean age 72 years, females 53%). The RI was an independent predictor of 30-day mortality (p=0.004). A RI ≤3.8 was associated with an increased death rate compared to higher RI values (15.4% vs 5.0%, OR 3.4, 95% CI 1.5–8.1). When the RI≤3.8 was integrated in the sPESI, the novel RI-model showed a good discriminatory power (c-statistics 0.703, 95% CI 0.603–0.803). In the 319 patients of the validation cohort (30-day mortality 6.9%, mean age 71 years, females 55%) the discriminatory power of the RI-model was confirmed (c-statistics 0.838, 95% CI 0.768–0.907). The RI-model and the 2014 ESC model had a c-statistics of 0.772 (95% CI 0.709–0.834) and of 0.687 (95% CI 0.620–0.753) in the overall population, respectively. Conclusion In this study, the RI independently predicted 30-day mortality in hemodynamically stable patients with acute PE. A clinical model including RI showed a better discriminatory value than 2014 ESC model and could be used for risk stratification in these patients.

The ageing heart: a target for interventions and aggressive pharmacotherapy 441 (MACE) defined as the composite of cardiovascular death, myocardial infarction and stroke was analyzed.Results: Clinically relevant bleedings (Bleeding Academic Research Consortium types 2, 3 or 5) were frequently observed (20.6%, n=181 patients) with one third of bleeding events occurring in the first month.Cutaneous and gastro-intestinal bleedings were the two predominant complications.There was no difference according to the P2Y12 inhibitor used between patients with a bleeding complication (prasugrel 5mg: 77.3%, prasugrel 10mg: 2.8% and clopidogrel 75mg: 19.9%) and those without (prasugrel 5mg: 77.9%, prasugrel 10mg: 2.5%, clopidogrel 75mg: 19.6%) (p=0.91).MACE occurred more frequently at one year in patients with a bleeding complication (16.6% vs 7.6%, adj.HR 2.04 (1.24; 3.38); p=0.005).Rates of myocardial infarction (Fig. 1A) and particularly stroke (Fig. 1B) were higher at one year after bleeding complications (9.9% vs 4.5%, adj.HR (95% CI): 2.40 (1.24; 4.66); p=0.0093 and 6.6% vs 1%, adj.HR (95% CI): 5.55 (2.04; 15.06); p=0.0008 respectively) without significant difference in death (6.6% vs 4.0%; HR (95% CI): 1.20 (0.57; 2.51); p=0.63).Predictive factors of major bleedings in the multivariate model were age >85 years [adj.HR (95% CI): 2.48 (1.25; 4.91); p=0.0093] and hemoglobin level (per gram of decrease) [adj.HR (95% CI): 1.45 (1.18; 1.79); p=0.0004].Conclusions: Clinically relevant bleedings were frequently observed in elderly patients and strongly associated with myocardial infarction and stroke.Age itself remained a predictive factor of bleeding in this population over the age of 75 years.

The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial.In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization.Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42).In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

Abstract Background In the direct oral anticoagulants (DOACs) era, extended anticoagulation after 6–12 months of treatment is an attractive strategy in patients with venous thromboembolism (VTE). Real-life data on the clinical benefit of DOAC over time is lacking. Purpose The aim of this study is to assess the effectiveness and safety of DOACs in patients with acute VTE treated for variable periods. Methods Data on patients with an objective diagnosis of acute VTE treated with DOACs were included in prospective cohort study. Study outcomes were recurrent VTE and major bleeding (ISTH definition). Results Overall, 934 patients were included (mean age 67.0±16.0, male gender 51.4%). Three-hundred and forty-six patients had a deep vein thrombosis (37.0%), 98 (10.5%) had isolated pulmonary embolism and 490 (52.5%) had both. One-hundred and sixty-nine patients (18.1%) had an active cancer, 59 (6.3%) a history of cancer and 365 patients (39.1%) an unprovoked VTE. During DOAC treatment (mean 21.6 months), 7 recurrent VTEs and 25 major bleedings occurred. In 546 and in 98 patients, DOAC was continued with full and reduced doses, respectively. In 290 patients (43.8% unprovoked, 13.8% active cancer, 42.4% associated with non-cancer risk factor), anticoagulants were withdrawn (average treatment duration 8.8 months) and 22 recurrent VTEs occurred over a follow-up off-treatment period of 31.9 months. In these patients, 2 episodes of major bleeding were observed. Overall, 201 patients died; fatal PE occurred in 4 and fatal bleeding in 1 patient. Time course for recurrent VTE according to 2019 ESC risk for recurrence is reported in the Figure. Conclusions In this cohort study, DOACs showed a good risk to benefit profile in the extended phase after an acute VTE event. Funding Acknowledgement Type of funding sources: None. Figure 1. Cumulative incidence of recurrent VTE

Background As mortality from pulmonary embolism (PE) decreases, the personal and societal costs among survivors are receiving increasing attention. Detailing this burden would support an efficient public health resource allocation. We aimed to provide estimates for the economic and disease burden of PE also accounting for long-term health care use and both direct and indirect costs beyond the acute phase. Methods and Results This is a cost-of-illness analysis with a bottom-up approach based on data from the PREFER in VTE registry (Prevention of Thromboembolic Events-European Registry in Venous Thromboembolism). We calculated direct (clinical events and anticoagulation) and indirect costs (loss of productivity) of an acute PE event and its 12-month follow-up in 2020 Euros. We estimated a disability weight for the 12-month post-PE status and corresponding disability adjusted life years presumably owing to PE. Disease-specific costs in the first year of follow-up after an incident PE case ranged between 9135 Euros and 10 620 Euros. The proportion of indirect costs was 42% to 49% of total costs. Costs were lowest in patients with ongoing cancer, mainly because productivity loss was less evident in this already burdened population. The calculated disability weight for survivors who were cancer free 12 months post-PE was 0.017, and the estimated disability adjusted life years per incident case were 1.17. Conclusions The economic burden imposed by PE to society and affected patients is considerable, and productivity loss is its main driver. The disease burden from PE is remarkable and translates to the loss of roughly 1.2 years of healthy life per incident PE case.