Pedro Monteiro

Background/Objectives: Edoxaban is a non-vitamin K antagonist oral anticoagulant indicated in patients with non-valvular atrial fibrillation to prevent stroke and systemic embolism. The objective was to obtain real-world data on the safety and effectiveness of edoxaban in routine care among patients with atrial fibrillation. Methods: ETNA-AF-Europe was a multinational, multicenter, prospective, post-authorization observational study. Its objectives were to assess the real-world safety of edoxaban (bleeding events and mortality) and its effectiveness by evaluating stroke, systemic embolic events, and cardiovascular events over 4 years. This article presents the results for Spain and Portugal. Results: In Spain and Portugal, 931 patients were included in the full analysis set. At baseline, 75.3% of patients were receiving edoxaban 60 mg, and 23.3% were receiving edoxaban 30 mg. Participants receiving 30 mg were older, more likely to be frail, and had a higher prevalence of comorbidities. The annualized rates of all-cause death (8.1% vs. 2.5%) and CV death (2.9% vs. 1.2%) were higher in patients receiving 30 mg than in patients receiving 60 mg. The annualized rates of bleeding events and stroke were higher in patients receiving edoxaban 30 mg. Conclusions: The results obtained in clinical practice verified the long-term effectiveness and safety of edoxaban, with low annualized event rates. The differences in outcomes according to edoxaban dose may be attributable to the underlying indication associated with each dose level and to clinical differences between patients.

Cardiovascular diseases are characterized by problems affecting the circulatory system, specifically the heart and blood vessels. This study evaluates the relationship between cardiovascular events and pharmacological treatment for Type II Diabetes Mellitus (T2DM). We recruited 227 individuals, 191 with T2DM (EG) and 36 pre-diabetics (CG), with a mean age of 70.3 years (SD=8.3), and 62 years (SD=10.3) respectively. The individuals were distributed into five groups concerning the following variables: body mass index (BMI), age, diagnosis age of T2DM, glycated hemoglobin value (HbA1c), Homeostatic model that estimates the function of β cells value (HOMA2-B), and Homeostatic model that estimates insulin resistance (HOMA-IR) value. At the time of data collection, there were no individuals with T1DM, so it was decided to use prediabetic individuals (with a high risk of developing T2DM). Group 1 had the pre-diabetic patients (15.9%), while diabetic individuals were divided into groups 2 (1.8%), 3 (17.6%), 4 (21.1%) and 5 (43.6%). It was possible to conclude that most of the patients in the different groups had a history of acute myocardial infarction (AMI). Regarding the prevalence of pharmacological treatment, it was possible to conclude that metformin was the most used drug in most of the groups. It was possible to create different groups and to observe the existence of dependency relationships between different cardiovascular events and pharmacological treatment. (www.actabiomedica.it)

Despite being primarily a disease of older patients, acute myocardial infarction (AMI) has been increasingly recognized in young individuals. This study sought to characterize and determine the prognosis of AMI in patients aged ≤ 45 years old. We retrospectively analyzed patients consecutively admitted to the coronary care unit with AMI. Two groups were identified: patients aged ≤ 45 and > 45 years old. A total of 5696 AMI patients were included in the analysis: median age of 70 (IQR 19) years and 68.6% (n = 3906) were male; 5.6% (n = 318) of patients were aged ≤ 45 years old. In contrast to the older patients, those aged ≤ 45 years old were more likely to be male (P < 0.001), presented more often with a history of smoking (P < 0.001), and family history of premature coronary artery disease (P < 0.001), but less often hypertension, hyperlipidemia, and diabetes. In coronary angiography, most younger patients presented a single-vessel disease (57.1%), more commonly affecting the left anterior descending artery (51.7%); left main involvement was rare (0.8%); and 14.2% presented MINOCA (vs. 11.4% of older patients). Regarding prognosis, 6.4% (n = 366) of patients died in the hospital and 24.2% (n = 1380) died during the 5-year follow-up. Younger patients had a lower risk of in-hospital mortality (OR 0.22, 95% CI 0.09–541, P = 0.001) and 5-year mortality (OR 0.12, 95% CI 0.06–0.201, P < 0.001), compared to the older patients. In conclusion, patients with premature AMI have a different proportion of risk factors, less extensive coronary artery disease, and more commonly present MINOCA, compared to the older patients.

The optimal management of myocardial infarction with nonobstructive coronary arteries (MINOCA) is still uncertain. This study sought to determine the association between pharmacological therapies after hospital discharge and the long-term prognosis of MINOCA patients. We analyzed patients consecutively admitted to the coronary care unit with myocardial infarction (MI). Multivariate analysis was performed to determine which drugs were implicated in the prognosis of MINOCA patients. The primary endpoint was all-cause mortality at 5 years. From a total of 3721 MI patients, MINOCA was identified in 11.6% (n = 430), of whom 56 (13.0%) experienced the primary endpoint. Median age was 66 years (IQR 19), and 51.6% (n = 222) of patients were male. At discharge, 81.2% of MINOCA patients were prescribed aspirin, 87.4% a statin, 78.6% beta-blockers, and 66.7% angiotensin-converting enzyme inhibitors (ACEI). MINOCA patients were less likely to be prescribed these medications compared to patients with obstructive coronary artery disease (all P < 0.001). 1.4% (n = 6) of MINOCA patients died in the hospital, and the 5-year mortality rate was 13.0% (n = 56). In multivariate Cox regression, treatment with ACEI at discharge was found to be independently associated with a 5-year mortality benefit (HR = 0.29, 95% CI 0.12–0.67, adjusted P = 0.004) in MINOCA patients. In conclusion, compared with patients with obstructive CAD, patients with MINOCA are less likely to be treated with secondary prevention drugs and are at lower risk of all-cause mortality during long-term follow-up. Treatment with ACEI seems to provide an additional mortality benefit in MINOCA patients.

Oral anticoagulation is highly effective in preventing ischaemic stroke in patients with atrial fibrillation, but 1–2% of the patients suffer an ischaemic stroke upon anticoagulation. Outcomes are further influenced by various factors, and recent research has focussed on identifying risk factors that could be helpful in predicting stroke outcomes in anticoagulated patients. This could further assist clinicians in timely identification and management of high-risk patients. The present analysis aims to assess the age-adjusted risk predictors of ischaemic stroke and systemic embolic events (SEE) (including transient ischaemic attack [TIA]) during two-year follow-up of unselected European patients with AF in the ETNA-AF-Europe registry. ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study conducted in 825 centres enrolling patients treated with edoxaban once daily in 10 European countries. Wald Chi square tested the association between risk predictors and stroke and SEE after adjusting for age, given that age is a well-known, strong predictor of stroke. A total of 13,417 patients with AF (edoxaban 60 mg: n=10,248; edoxaban 30 mg: n=3169) completed the two-year follow-up. The mean age was 73.6±9.5 years, with ∼84% of the patients aged over 65 years. The mean weight was 81.0±17.3 kg, estimated glomerular filtration rate was 74.4±30.5 ml/min/1.73m² and males were 56.6%. The mean CHA2DS2-VASc and HAS-BLED scores were 3.2 and 2.5, respectively. Univariate analysis demonstrated that history of TIA at baseline was the strongest age-adjusted predictor of stroke and SEE (Wald Chi-square: 77.69; p<0.0001) (Figure 1), followed by CHA2DS2-VASc score (41.09; p<0.0001) (Figure 2), history of ischaemic stroke (29.47; p<0.0001), history of any stroke (all strokes combined including stroke of unknown/unspecified type) (29.18; p<0.0001), subjective frailty as assessed by physician (20.60; p<0.0001), and HAS-BLED score (17.22; p<0.0001). History of TIA, CHA2DS2-VASc score, history of stroke, frailty and HAS-BLED score are independently associated with an increased age-adjusted risk of ischaemic stroke, TIA and SEE in anticoagulated patients with AF. These findings highlight the importance of optimising anticoagulation therapy in secondary prevention of TIA and in patients with high CHA2DS2-VASc scores, ensuring the correct use of NOACs - adherence and correct dosing - in this high-risk population. These findings also suggest that additional therapies could be needed to prevent stroke in this population. Figure 1. History of TIA as a predictor Figure 1. History of TIA as a predictor Figure 2. CHA2DS2-VASc score as a predictor Figure 2. CHA2DS2-VASc score as a predictor

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are a preferred treatment option over warfarin for anticoagulation in patients with atrial fibrillation (AF). Management decisions for thromboprophylaxis in AF need to balance the risk of stroke against the risk of bleeding. Various patient characteristics have been identified as independent risk factors for bleeding. A substantial number of bleeding events might be prevented if independent predictors of bleeding were identified. Purpose: The present analysis aims at assessing age-adjusted risk predictors of major bleeding during two-year follow-up of unselected European patients with AF in the ETNA-AF-Europe registry. Methods: ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study conducted in 825 centres enrolling patients treated with edoxaban once daily in 10 European countries. Wald Chi square tested the association between risk predictors and major bleeding after adjusting for age, given that age is a well-known, strong predictor of anticoagulation-related bleeding in patients with AF. Results: Overall, 13,417 patients with AF (edoxaban 60 mg: n=10,248; edoxaban 30 mg: n=3169) completed the two-year follow-up. The mean age was 73.6±9.5 years, with ∼84% of the patients aged over 65 years. Mean CHA2DS2-VASc and HAS-BLED scores were 3.2 and 2.5, respectively. 438 (3.3%) patients had a history of bleeding events at baseline, of which 138 (1.0%) had a history of major bleeding event. Univariate analysis demonstrated that recalculated glomerular filtration rate (Cockcroft-Gault Equation) (GFR-CG) at baseline was the strongest age-adjusted predictor of major bleeding (Wald Chi-Square: 31.84; p<0.0001) (Figures 1 and 2), followed by history of major or clinically relevant non-major (CRNM) bleeding (24.08; p<0.0001), HAS-BLED score (21.10; p<0.0001), history of heart failure (derived) (16.59; p<0.0001), subjective frailty as assessed by physician (17.35; p=0.0002), history of major bleeding (14.14; p=0.0002), chronic obstructive pulmonary disease (COPD) (12.84; p=0.0003), CHA2DS2-VASc (12.14; p=0.0005), history of myocardial infarction (MI) (7.79; p=0.005), and left ventricular ejection fraction (LVEF) categorised by 40% (5.45; p=0.02). Conclusion: Bleeding events on therapy with edoxaban can be predicted by quantifying kidney disease and capturing information on heart failure, frailty, prior bleeding, chronic obstructive lung disease and history of myocardial infarction. These data highlight the need for optimal management of anticoagulation therapy and close follow-up of patients with such risk profiles. Funding Acknowledgement: Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH Figure 1. GFR-CG as a predictor of major bleedingFigure 2. Predictors of major bleeding

Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies. Ibrutinib has an established favorable toxicity profile with up to 8 years...

The risks of cardio-renal complications of diabetes increase with age. In the EMPA-REG OUTCOME® trial, empagliflozin reduced cardiovascular (CV) mortality by 38% in patients with type 2 diabetes (T2D) and CV disease. Here we compare outcomes with empagliflozin in older patients in EMPA-REG OUTCOME. Patients with T2D and CV disease were randomised to empagliflozin 10 or 25 mg, or placebo plus standard of care. In post hoc analyses, risks of 3-point major adverse CV events (3P-MACE: composite of CV death, non-fatal myocardial infarction (MI) or non-fatal stroke), CV death, hospitalisation for heart failure, all-cause mortality, all-cause hospitalisation and incident/worsening nephropathy were evaluated for empagliflozin versus placebo by baseline age (P ≥ 0.05 for interactions) except 3P-MACE. The 3P-MACE hazard ratios (HRs) were 1.04 (95% confidence interval [CI] 0.84, 1.29), 0.74 (0.58, 0.93) and 0.68 (0.46, 1.00) in patients aged P = 0.047 for treatment-by-age group interaction). Corresponding CV death HRs were 0.72 (95% CI 0.52, 1.01), 0.54 (0.37, 0.79) and 0.55 (0.32, 0.94), respectively (P = 0.484 for treatment-by-age group interaction). Across age categories, empagliflozin AEs reflected its known safety profile. Rates of bone fractures, renal AEs and diabetic ketoacidosis were similar between empagliflozin and placebo across age categories. In the EMPA-REG OUTCOME trial, empagliflozin reduced risks of CV mortality, heart failure and renal outcomes, supporting its cardio-renal benefits in older patients.