Clinical Performance and Persistence on Dual Pathway Inhibition with Rivaroxaban and Aspirin in Real-World Setting.

ABSTRACT: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.

Dual Pathway Inhibition with Rivaroxaban and Aspirin Reduces Inflammatory Biomarkers in Atherosclerosis.

ABSTRACT: Dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) reduces the occurrence of cardiovascular (CV) events; however, the underlying mechanisms explaining these latter CV benefits are not clearly understood. Our explorative observational study aimed to evaluate the effect of dual pathway inhibition on plasma inflammation and coagulation markers among real-world patients with CAD and/or PAD. We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin 100 mg once daily (OD) and rivaroxaban 2.5 mg twice daily (TD). Clinical evaluation and laboratory analyses, including hemoglobin, renal function (creatinine, urea, and cystatin-C), coagulation markers (INR and aPTT), inflammation markers (IL-6, CRP, lipoprotein-associated phospholipase A2, and copeptin), and growth differentiation factor-15 (GDF-15), were conducted at baseline, before starting treatment, and at 4 and 24 weeks after study drug administration. Fifty-four consecutive patients (mean age 66 ± 7 years; male 83%) who completed the 6-month follow-up were included. At 24-week follow-up, a statistically significant reduction in IL-6 serum levels [4.6 (3.5-6.5) vs. 3.4 (2.4-4.3) pg/mL ; P = 0.0001] and fibrinogen [336 (290-390) vs. 310 (275-364) mg/dL; P = 0.04] was shown; moreover, a significant increase in GDF-15 serum level [1309 (974-1961) vs. 1538 (1286-2913) pg/mL; P = 0.002] was observed. Hemoglobin, renal function, and cardiovascular homeostasis biomarkers remain stable over the time. The anti-Xa activity at both [0.005 (0-0.02) vs. 0.2 (0.1-0.34); P < 0.0001) significantly increased. The dual pathway inhibitions with low-dose rivaroxaban and aspirin in patients with CAD and/or PAD were associated with the reduction of inflammation biomarkers.

Oral Anticoagulation for Atrial Fibrillation in Octogenarians Across the Renal Function Spectrum.

PURPOSE: Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. METHODS: Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m2. The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. RESULTS: A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m2, a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m2, DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. CONCLUSION: DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Clinical impact of oral anticoagulation among octogenarians with atrial fibrillation and anaemia.

Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in elderly patients (> or = 80 years-old) with atrial fibrillation (AF) and concomitant anaemia. Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized as anaemic and non-anaemic. The primary outcome was the occurrence of overall bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events (a composite of ischemic stroke, transient ischemic attack and systemic embolism). The secondary safety and effectiveness outcomes were major, minor bleedings and mortality, respectively. A total of 958 patients were included in the study, 120 (12.5%) were anaemic; among them, 93 patients (76.6%) were treated with VKAs and 28 (23.3%) with DOAC. Kaplan-Meier curves for major bleedings showed significant differences between anemic- and non-anemic groups (log-rank p = 0.005). In multivariate analysis, among patients on OAC, anaemia was independently associated with major bleeding (HR 2.36; 95% IC 1.2-4.4; p = 0.006), intracranial hemorrhages (HR 3.81; 95% IC 1.35-10.7; p = 0.01) and minor bleedings (HR 2.40; 95%IC 1.1-5.2; p = 0.02); these associations were not confirmed in the DOACs subgroup. No difference in survival was shown between anaemic- and non-anaemic groups and among anaemic patients, between DOAC and VKAs subgroups. Anaemic octogenarians with AF on OAC therapy showed a significantly increased risk of major bleedings, in particular ICH, and mortality compared to non-anaemic.

Subcutaneous versus transvenous implantable cardioverter-defibrillator among drug-induced type-1 ECG pattern Brugada syndrome: a propensity score matching analysis from IBRYD study.

No real-world data are available about the complications rate in drug-induced type 1 Brugada Syndrome (BrS) patients with an implantable cardioverter-defibrillator (ICD). Aim of our study is to compare the device-related complications, infections, and inappropriate therapies among drug-induced type 1 BrS patients with transvenous- ICD (TV-ICD) versus subcutaneous-ICD (S-ICD). Data for this study were sourced from the IBRYD (Italian BRugada sYnDrome) registry which includes 619 drug-induced type-1 BrS patients followed at 20 Italian tertiary referral hospitals. For the present analysis, we selected 258 consecutive BrS patients implanted with ICD. 198 patients (76.7%) received a TV-ICD, while 60 a S-ICD (23.4%). And were followed-up for a median time of 84.3 [46.5-147] months. ICD inappropriate therapies were experienced by 16 patients (6.2%). 14 patients (7.1%) in the TVICD group and 2 patients (3.3%) in S-ICD group (log-rank P = 0.64). ICD-related complications occurred in 31 patients (12%); 29 (14.6%) in TV-ICD group and 2 (3.3%) in S-ICD group (log-rank P = 0.41). ICD-related infections occurred in 10 patients (3.88%); 9 (4.5%) in TV-ICD group and 1 (1.8%) in S-ICD group (log-rank P = 0.80). After balancing for potential confounders using the propensity score matching technique, no differences were found in terms of clinical outcomes between the two groups. In a real-world setting of drug-induced type-1 BrS patients with ICD, no significant differences in inappropriate ICD therapies, device-related complications, and infections were shown among S-ICD vs TV-ICD. However, a reduction in lead-related complications was observed in the S-ICD group. In conclusion, our evidence suggests that S-ICD is at least non-inferior to TV-ICD in this population and may also reduce the risk of lead-related complications which can expose the patients to the necessity of lead extractions.

The prognostic role of interatrial block among COVID-19 patients hospitalized in medicine wards.

INTRODUCTION: Some abnormal electrocardiographic findings were independently associated with increased mortality in patients admitted for COVID-19; however, no studies have focussed on the prognosis impact of the interatrial block (IAB) in this clinical setting. The aim of our study was to assess the prevalence and clinical implications of IAB, both partial and advanced, in hospitalized COVID-19 patients. MATERIALS: We retrospectively evaluated 300 consecutive COVID-19 patients (63.22 ± 15.16 years; 70% males) admitted to eight Italian Hospitals from February 2020 to April 2020 who underwent twelve lead electrocardiographic recording at admission. The study population has been dichotomized into two groups according to the evidence of IAB at admission, both partial and advanced. The differences in terms of ARDS in need of intubation, in-hospital mortality and thromboembolic events (a composite of myocardial infarction, stroke and transient ischaemic attack) have been evaluated. RESULTS: The presence of IAB was noticed in 64 patients (21%). In the adjusted logistic regression model, the partial interatrial block was found to be an independent predictor of ARDS in need of intubation (HR: 1.92; p: .04) and in-hospital mortality (HR: 2.65; p: .02); moreover, the advanced interatrial block was an independent predictor of thrombotic events (HR: 7.14; p < .001). CONCLUSIONS: Among COVID-19 patients hospitalized in medical wards, the presence of interatrial block is more frequent than in the general population and it might be useful as an early predictor for increased risk of incident thrombotic events, ARDS in need of intubation and in-hospital mortality.

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients.

PURPOSE: The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. METHODS: This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. RESULTS: Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation.

PURPOSE: Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. METHODS: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. RESULTS: A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45-6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45-9.10); p < 0.001] and body mass index [OR = 1.27 (1.14-1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36-96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61-0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62-0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43-28); p = 0.039]. There wasn't significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). CONCLUSION: In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs' overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

CRT implantation after transvenous lead/device extraction (TLE) in a patient with COVID-19: Endocarditis triggered by syndrome coronavirus 2 (SARS-COV-2) infection? A case report.

In the era of coronavirus disease 2019 (COVID-19), the management of cardiac implantable electronic devices infections with concomitant viral infection has not been completely defined yet. In this explorable context, we report the first experience of a Cardiac resynchronization therapy with defibrillator (CRT-D) implantation after transvenous lead extraction for endocarditis in a COVID-19 patient. We describe both the measures and procedures implemented to reduce the cross-infection in the operating room and our clinical practice to improving procedure effectiveness on patient care.