Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network.

BACKGROUND: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. OBJECTIVE: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. METHODS: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017-2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). RESULTS: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. CONCLUSIONS: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

One-year clinical outcome of patients with left ventricular thrombus after acute myocardial infarction discharged on triple or dual antithrombotic therapy.

In patients with left ventricular thrombus (LVT) after acute myocardial infarction (MI), both anticoagulant and antiplatelet therapies are needed. It is unknown whether dual antithrombotic therapy (DAT) is able to reduce the incidence of bleeding complications without significantly increasing the number of thromboembolic events, compared to triple antithrombotic therapy (TAT). We retrospectively evaluated all post-MI patients with LVT discharged on TAT or DAT from our tertiary hospital in the last decade. The primary outcome was the occurrence of all-cause mortality, thromboembolic events, hospitalizations for re-MI or heart failure and any bleeding at 1 year. A propensity-score matching was performed in order to compare the primary outcome between TAT and DAT. Out of 2564 acute MI patients, 83 (3.2%) had an LVT at echocardiography: 51 (61.4%) discharged on TAT and 32 (38.6%) on DAT. At clinical follow-up, completed in 93% of cases, the incidence of the primary outcome was 18.2% (25.5% in TAT and 6.7% in DAT group; p = 0.04). More than 2/3 of the events included in the primary outcome were related to bleeding complications and occurred during the first month from hospital discharge. In the matched cohort of 42 patients with follow-up data available, the primary outcome occurred in 9 (42.9%) patients in the TAT and 2 (9.5%) in the DAT group (p = 0.03). In post-MI patients with LVT, DAT seems more effective than TAT in reducing clinical outcome, especially early bleeding complications. A randomized study is warranted to confirm this hypothesis.

The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

Is percutaneous coronary intervention safe during uninterrupted direct oral anticoagulant therapy in patients with atrial fibrillation and acute coronary syndromes?

OBJECTIVES: No data on optimal management of patients with acute coronary syndromes (ACS) on long-term direct oral anticoagulants (DOACs) undergoing percutaneous coronary intervention (PCI) are available. Using the data of the Management of Antithrombotic TherApy in Patients with Chronic or DevelOping AtRial Fibrillation During Hospitalization for PCI study, we sought to compare the outcome of patients with ACS and atrial fibrillation (AF) who underwent PCI during uninterrupted DOAC (UDOAC group) and those who interrupted DOAC before PCI (IDOAC group). METHODS: The primary outcomes of our analysis were the incidence of major adverse cardiovascular events (MACEs), a composite of death, cerebrovascular events, recurrent myocardial infarction or revascularisation and net adverse clinical events (NACEs), including major bleeding, at 6 months. RESULTS: Among the 132 patients on long-term DOAC, 72 (54.6%) underwent PCI during UDOAC and 60 (45.4%) after IDOAC. The mean CHA2DS2-VASc score was 3.8±1.7 and 3.9±1.3 (p=0.89), while the HAS-BLED score was 2.5±1.0 and 2.5±0.9 (p=0.96), in UDOAC and IDOAC groups, respectively. The median time from hospital admission to PCI was 9.5 (IQR: 2.0-31.5) hours in UDOAC and 45.5 (IQR: 22-5-92.0) hours in IDOAC group (p<0.0001). A radial approach was used in 92%, and a drug-eluting stent was implanted in 98% of patients. At 6 months, the rates of MACE (13.9% vs 16.7%) and NACE (20.8% vs 21.7%) did not differ between UDOAC and IDOAC groups. At multivariable analysis, increasing CHA2DS2-VASc score (HR: 1.39; 95% CIs 1.05 to 1.83; p=0.02) resulted as the only independent predictor of NACE. CONCLUSIONS: Our study shows that PCI is a safe procedure during UDOAC in patients with concomitant ACS and AF.

A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index.

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

Effectiveness of fondaparinux vs unfractionated heparin following percutaneous coronary intervention in survivors of out-of-hospital cardiac arrest due to acute myocardial infarction.

AIM: There is no specific evidence on the antithrombotic management of survivors of out-of-hospital cardiac arrest (OHCA) due to acute myocardial infarction (AMI). We sought to compare the short-term outcome of unfractioned heparin (UFH) vs fondaparinux in OHCA survivors due to AMI admitted in our Institution in the last decade. METHODS: We performed a retrospective cohort study on survivors of OHCA due to AMI managed with UFH or fondaparinux during the hospitalization. The primary outcome was the occurrence of any bleeding, all-cause mortality, cerebrovascular accidents, re-MI, and unplanned revascularization at 1 month. A propensity-score matching was performed to compare the outcome between UFH and fondaparinux. RESULTS: Out of 2083 AMI patients undergoing successful PCI, OHCA was present in 94 (4.5%): 41 (43.6%) treated with UFH and 53 (56.4%) with fondaparinux. At clinical follow-up, the incidence of the primary outcome was 65.9% in UFH and 35.8% in fondaparinux group (p = 0.007). More than half of the events included in the primary outcome were related to bleeding complications. In the matched cohort of 56 patients, the primary outcome occurred in 46.4% and 25.0% (p = 0.16), while bleeding was present in 32.1% and 7.1% (p = 0.04), in the UFH and fondaparinux group, respectively. CONCLUSIONS: The present analysis suggests that fondaparinux is safer than UFH in the management of OHCA due to AMI by reducing early bleeding complications at one month.

Fondaparinux During Intra-Aortic Balloon Pump Counterpulsation in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Although anticoagulation with unfractionated heparin (UFH) is commonly used during intra-aortic balloon pump (IABP) counterpulsation to prevent thromboembolic events, no data or guidelines exist to support this strategy, especially in the setting of acute myocardial infarction (AMI). This study sought to compare the short-term outcome of UFH vs fondaparinux in AMI patients who underwent successful percutaneous coronary intervention (PCI) and IABP insertion. METHODS: The anticoagulation therapy of revascularised AMI patients who received IABP counterpulsation and admitted to a tertiary hospital in the last decade was retrospectively evaluated. The primary outcome was the occurrence of all-cause mortality, stroke or transient ischaemic attack, reinfarction, unplanned revascularisation, major or minor limb ischaemia, and any bleeding at 1 month. Propensity score matching was performed to compare the primary outcome between UFH and fondaparinux. RESULTS: Of 1,355 AMI survivors at 2 days after hospital admission and who underwent successful PCI, an IABP was inserted in 197 (14.5%): 72 (36.5%) were treated with UFH and 125 (63.5%) with fondaparinux (2.5 mg o.d.). At clinical follow-up, completed in 98.5% of cases, the incidence of the primary outcome was 22.5% in UFH and 5.7% in fondaparinux groups (p=0.0009). More than two-thirds of the events included in the primary outcome were related to early bleeding complications. In the matched cohort of 62 patients, the primary outcome occurred in 14 (45.2%) patients in the UFH and two (6.5%) in the fondaparinux group (p=0.01). CONCLUSIONS: This study suggested that fondaparinux is safer, by reducing early bleeding complications at one month, than UFH in the management of IABP.

Diagnosis of Primary Cardiac T-cell Lymphoma: Feasibility and Safety of Endomyocardial Biopsy Guided by Pre-acquired Cardiovascular Magnetic Resonance.

BACKGROUND: Multimodality imaging of a cardiac mass lesion may raise suspicion of a primitive cardiac lymphoma (PCL). However, a definitive diagnosis requires histopathological confirmation. METHODS: This report describes the methodology we used to perform biopsy sampling of a cardiac mass lesion affecting a 45-year-old man. In order to increase endomyocardial biopsy diagnostic accuracy, we used pre-acquired cardiac magnetic resonance (CMR) images to guide the bioptome on a cardiac site overtly infiltrated by the suspected tumour. The right ventricular outflow tract was identified as the target site for biopsy sampling. To reduce the risk of the procedure, the biopsy was performed at a safe distance from the tip of a diagnostic quadripolar catheter positioned at the level of the pulmonary valve, previously identified by pacing manoeuvres. The reported approach demonstrated safety and diagnostic accuracy, allowing the identification of an extremely rare PCL subtype of T-cell origin. CONCLUSION: Biopsy sampling of a suspected tumour may be safely and accurately performed using pre-acquired CMR images to guide the bioptome on the target site. LEARNING POINTS: Multimodal imaging techniques capable of tissue characterization may raise suspicion of a primary cardiac lymphoma (PCL).However, the final diagnosis of PCL can be confirmed only by histological examination of a tissue sample.Biopsy sampling of the mass lesion may be accurately guided by previously acquired cardiac magnetic resonance images.

Impact of history of depression on 1-year outcomes in patients with chronic coronary syndromes: An analysis of a contemporary, prospective, nationwide registry.

BACKGROUND: Depression is common in patients with acute cardiovascular conditions and it is associated with adverse clinical events. METHODS: Using the data from a nationwide, prospective registry on patients with chronic coronary syndromes (CCS), we assessed the impact of depression on major adverse cardiovascular events (MACE), a composite of all-cause death and hospitalization for myocardial infarction, revascularization, heart failure or stroke, and quality of life (QoL) at 1-year follow-up. RESULTS: From the 5070 consecutive CCS patients enrolled in the registry, 531 (10.5%) presented a history of depression and the remaining 4539 (89.5%) did not. At 1 year (median 369; IQR 362-378 days) from enrolment, the incidence of the primary composite outcome was 9.8% for patients with a history of depression and 7.2% for non-depressed patients (p = 0.03). Patients with history of depression had a significantly higher rate of all-cause mortality (3.0% vs 1.4%; p = 0.004) and hospital admission for heart failure (3.4% vs 1.3%; p = 0.0002) compared to the group without depression. However, history of depression did not result as an independent predictor of MACE at multivariable analysis [hazard ratio 1.17, 95% confidence interval (0.87-1.58), p = 0.31]. Depressed patients had worse QoL according to all domains of the EQ. 5D-5L questionnaire as compared to non-depressed patients (all p < 0.001), at both enrolment and follow-up. CONCLUSIONS: In this contemporary, large cohort of consecutive patients with CCS, patients with a history of depression experienced a two-fold rate of mortality, a higher incidence of MACE and a worse QoL at 1-year follow-up, compared to non-depressed patients.

COMPASS criteria applied to a contemporary cohort of unselected patients with stable coronary artery diseases: insights from the START registry.

AIMS: Recently, the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial demonstrated that dual therapy reduced cardiovascular outcomes compared with aspirin alone in patients with stable atherosclerotic disease. METHODS AND RESULTS: We sought to assess the proportion of patients eligible for the COMPASS trial and to compare the epidemiology and outcome of these patients with those without COMPASS inclusion or with any exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease. Among the 4068 patients with detailed information allowing evaluation of eligibility, 1416 (34.8%) did not fulfil the inclusion criteria (COMPASS-Not-Included), 841 (20.7%) had exclusion criteria (COMPASS-Excluded), and the remaining 1811 (44.5%) were classified as COMPASS-Like. At 1 year, the incidence of major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, and stroke, was 0.9% in the COMPASS-Not-Included and 2.0% in the COMPASS-Like (P = 0.01), and 5.0% in the COMPASS-Excluded group (P < 0.0001 for all comparisons). Among the COMPASS-Like population, patients with multiple COMPASS enrichment criteria presented a significant increase in the risk of MACE (from 1.0% to 3.3% in those with 1 and ≥3 criteria, respectively; P = 0.012), and a modest absolute increase in major bleeding risk (from 0.2% to 0.4%, respectively; P = 0.46). CONCLUSION: In a contemporary real-world cohort registry of stable coronary artery disease, most patients resulted as eligible for the COMPASS. These patients presented a considerable annual risk of MACE that consistently increases in the presence of multiple risk factors.

Temporal Trends in Invasive Management and In-Hospital Mortality of Patients With Non-ST Elevation Acute Coronary Syndromes and Chronic Kidney Disease.

We analyzed data from 4 nationwide prospective registries of consecutive patients with acute coronary syndromes (ACS) admitted to the Italian Intensive Cardiac Care Unit network between 2005 and 2014. Out of 26 315 patients with ACS enrolled, 13 073 (49.7%) presented a diagnosis of non-ST elevation (NSTE)-ACS and had creatinine levels available at hospital admission: 1207 (9.2%) had severe chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <30), 3803 (29.1%) mild to moderate CKD (eGFR 31-59), and 8063 (61.7%) no CKD (eGFR > 60 mL/min/1.73 m2). Patients with severe CKD had worse clinical characteristics compared with those with mild-moderate or no kidney dysfunction, including all the key predictors of mortality (P < .0001) which became worse over time (all P < .0001). Over the decade of observation, a significant increase in percutaneous coronary intervention rates was observed in patients without CKD (P for trend = .0001), but not in those with any level of CKD. After corrections for significant mortality predictors, severe CKD (odds ratio, OR: 5.49; 95% CI: 3.24-9.29; P < .0001) and mild-moderate CKD (OR: 2.33; 95% CI: 1.52-3.59; P < .0001) remained strongly associated with higher in-hospital mortality. The clinical characteristics of patients with NSTE-ACS and CKD remain challenging and their mortality rate is still higher compared with patients without CKD.

External applicability of the ISCHEMIA trial: an analysis of a prospective, nationwide registry of patients with stable coronary artery disease.

AIMS: We sought to assess the proportion of patients eligible for the ISCHEMIA trial and to compare the characteristics and outcomes of these patients with those without ISCHEMIA inclusion or with ISCHEMIA exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Among the 5,070 consecutive patients enrolled in the START registry, 4,295 (84.7%) did not fulfil the inclusion criteria (ISCHEMIA-Not Included or ISCHEMIA-Unclassifiable), 582 (11.5%) had exclusion criteria (ISCHEMIA-Excluded), and the remaining 193 (3.8%) were classified as ISCHEMIA-Like. At one year, the incidence of the primary outcome, a composite of death from cardiovascular (CV) causes, myocardial infarction (MI), or hospitalisation for unstable angina and heart failure, was 0.5% in the ISCHEMIA-Like versus 3.3% in other patients (p=0.03). The composite secondary outcome of CV mortality and MI occurred in 0.5% of the ISCHEMIA-Like patients and in 1.4% of the remaining patients (p=0.1). CONCLUSIONS: In a contemporary real-world cohort of stable CAD patients, only 4% resulted in being eligible for the ISCHEMIA trial. These patients presented an extremely low annual risk of adverse events, especially when compared with other groups of stable CAD patients.

Statins plus ezetimibe in the era of proprotein convertase subtilisin/ kexin type 9 inhibitors.

Statins are first­line agents used in patients with dyslipidemia, which show established benefits in reducing low­density lipoprotein cholesterol (LDL­C) levels and decreasing the rate of cardiovascular events. However, a considerable number of patients on statins do not achieve target LDL­C levels, even at maximally tolerated statin doses, or are intolerant to intensive statin therapy. These patients can benefit from the addition of a nonstatin lipid­lowering agent, and recent cholesterol guidelines have put greater focus on combination lipid­lowering therapy. In patients who cannot achieve target treatment goals with statin therapy alone, the addition of a cholesterol absorption inhibitor, ezetimibe, leads to further LDL­C reduction with good tolerability and decreases cardiovascular morbidity and mortality. The more recent proprotein convertase subtilisin­like / kexin type 9 (PCSK­9) inhibitors can lower LDL­C by additional 45% to 65% and are also well tolerated. These complementary approaches for LDL­C lowering in patients treated with statins decrease LDL­C levels more effectively than statin monotherapy. As no threshold level has been established below which LDL­C lowering benefits disappear, the early application of a combination treatment strategy may lead to improved cardiovascular outcomes, particularly in high­risk patients. This review examines the rationale, advantages, and potential barriers to combination lipid­lowering therapy with reference to the current guideline recommendations.

Adverse Drug Reactions during Real-Life Use of Direct Oral Anticoagulants in Italy: An Update Based on Data from the Italian National Pharmacovigilance Network.

BACKGROUND: The availability of direct oral anticoagulants (DOAC) in clinical practice has transformed the health care provided to patients for the prevention and treatment of thromboembolism. Safety and efficacy data guide clinicians in the choice of the drug used. To date, no evidence is available from head-to-head trials comparing different DOAC with regard to safety and efficacy; information is mainly derived from several meta-analyses and real-life studies. Conclusions from these studies are inconsistent and unsatisfactory. The evaluation of self-reported adverse drug reactions (ADR) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision-making. OBJECTIVE: To analyze potential suspected ADR of DOAC using a previously described risk index (RI) in daily clinical practice in Italy. METHODS: The National Pharmacovigilance Network database (from the AIFA website) was searched in order to retrieve information on all ADR related to oral anticoagulants occurring from 2013 to 2018. The ADR RI for each drug was calculated, where an RI = 1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (safer DOAC). The following DOAC molecules were considered: dabigatran, rivaroxaban, apixaban, and edoxaban. RESULTS: The results showed that rivaroxaban is the DOAC with the lowest RI among the 4 molecules available today in Italy. CONCLUSIONS: Based on the RI, we identified rivaroxaban as the DOAC having the best safety profile.

Early Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure After Acute Decompensation: A Case Series Analysis.

BACKGROUND AND OBJECTIVE: Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. METHODS: Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. RESULTS: In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. CONCLUSIONS: Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers.

[Appropriateness criteria for the management of lipid-lowering therapy with alirocumab in high cardiovascular risk patients. The opinion of a multidisciplinary group of Italian experts]. / Criteri di appropriatezza nella gestione della terapia ipocolesterolemizzante con alirocumab nel paziente ad alto rischio cardiovascolare. L'opinione di un gruppo multidisciplinare di esperti italiani.

High levels of LDL cholesterol (LDL-C) represent a causal factor for cardiovascular diseases on an atherosclerotic basis, with a direct correlation between these and mortality or cardiovascular events, such that the reduction of both is associated proportionally and linearly with the reduction of LDL-C.Statins and ezetimibe are used for LDL-C lowering but may not be sufficient to achieve the targets defined by the ESC/EAS guidelines, which recommend use of PCSK9 inhibitors for further LDL-C reduction in patients not at goal.This project submitted 86 clinical scenarios to a group of experts, cardiologists, internists and lipidologists, collecting their opinion on the appropriateness of different behaviors and decisions. We used the RAND/UCLA method of assessing the appropriateness of clinical interventions, validated to combine the best scientific evidence available with expert judgment. To this end, the benefit-risk ratio was evaluated in the proposed clinical scenarios. Each indication was classified as "appropriate", "uncertain" or "inappropriate" based on the average score given by the participants.This document presents the results of a consensus process that led to the development of recommendations for the management of clinical scenarios on the treatment of patients with dyslipidemia, which cannot always be solved with scientific evidence alone.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and High Thromboembolic Risk. A Systematic Review.

Background: The aim of the study was to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in a subgroup of patients with atrial fibrillation (AF), CHADS2 score ≥3, advanced age, and heart failure (HF) coming from the main DOACs randomized clinical trials. Methods: We searched MEDLINE, MEDLINE In-Process, and Other Non-Indexed Citations, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. English-language articles published from 2002 to March 2019 dealing with DOACs for preventing thrombotic events in AF were considered. We did not conduct any statistical analyses, as indirect comparison between DOACs represents hypothesis generators. Results: This systematic review was restricted to the subgroup of patients with CHADS2 score ≥3 (n = 31,203), elderly (n = 24,788), and with HF (n = 29,297) derived from the pivotal trials. Risk index (RI) was calculated. The RI for stroke/systemic embolism was similar in all of the patients treated with DOACs or warfarin. The lowest RI was in rivaroxaban patients (CHADS2 score ≥3: RI = 0.04; elderly: RI = 0.09; HF: RI = 0.05). The RIs for bleeding were higher in patients treated with dabigatran (CHADS2 score ≥3: RI110 = 0.23; elderly: RI110 = 0.22; HF: RI110 = 0.16; CHADS2score ≥3: RI150 = 0.30; elderly: RI150 = 0.24; HF: RI150 = 0.16). The bleeding RIs were higher with apixaban (CHADS2 score ≥3: RI = 0.23; elderly: RI = 0.25; HF: RI = 0.14) and dabigatran (CHADS2 score ≥3: RI = 0.28; elderly: RI = 0.21; HF: RI = 0.19). Conclusions: The use of DOACs is a reasonable alternative to vitamin K antagonists in AF patients with CHADS2 score ≥3, advanced age, and HF. The RI constitutes a useful, additional tool to facilitate clinicians in choosing DOACs or warfarin in particular category of AF patients.

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study.

BACKGROUND: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). HYPOTHESIS: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. METHODS: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. RESULTS: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. CONCLUSIONS: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI.