Management of anticoagulation in atrial fibrillation patients in Italy: insight from the <i>Atrial Fibrillation-Survey on Anticoagulated Patients Register</i> (AF-START)

The survey on anticoagulated patients register (START-Register) is an independent, prospective, inception-cohort observational study aimed at providing information on patients on vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) in Italy. In this study, we describe the cohort of atrial fibrillation (AF) patients in the START-Register and report outcomes and changes in anticoagulant prescription from 2011 to 2021. The study included 11,078 AF patients, enrolled in 47 Italian centers distributed all over the Country; the median age was 77 years (range 18-99 years); 6029 (54.3%) were men; 5135 (46.4%) were on VKAs, and 5943 (53.6%) were on DOACs. Warfarin was the most prescribed VKA (98.4%), and apixaban was the most prescribed DOAC (31.6%). Among DOAC users, 4022 (67.7%) patients were naive to anticoagulation, and 2562 (43.1%) patients were treated with a reduced dose. DOAC patients were significantly older than VKA patients (median age 79 years vs 76 years respectively, P<0.001), but no gender difference was detected. The mean CHA2DS2VASc score was higher in DOAC users than in VKA users (3.7 vs 3.6; P=0.03). The mean HAS-BLED score was not different between the two groups. During follow-up, 542 bleeding events were recorded [2.44 per 100 patient-years (pt-yrs)]; 240 were major (1.08 per 100 pt-yrs), and 301 were clinically relevant non-major bleedings (1.34 per 100 pt-yrs). 146 thrombotic events were recorded during follow-up (0.66 per 100 pt-yrs). The total mortality rate was 3.5 per 100 pt-yrs; the mortality rate was 4.54 per 100 pt-yrs among patients on VKAs and 2.31 per 100 pt-yrs among patients on DOACs. During the last 10 years, in Italy, AF patient management has changed with the large spread of DOACs all over the Country. DOAC patients are frequently treated with reduced doses and show a lower mortality rate in comparison to patients on VKAs

Very elderly patients with venous thromboembolism on oral anticoagulation with VKAs or DOACs: Results from the prospective multicenter START2-Register Study

Few data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE).Introduction: Few data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE). Methods: We carried out a prospective cohort study on VTE patients aged 6585 years enrolled in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) on treatment with VKAs or DOACs, with the aim to evaluate mortality, bleeding and thrombotic rates (venous and arterial). Results: We enrolled 272 patients, 58.7% on VKA and 41.3% on DOACs. Baseline characteristics were similar between treatment groups, with a higher prevalence of renal failure in VKAs patients and of a history of bleeding and previous stroke/TIA in DOACs patients. During follow-up of 429 patient-years, 15 major and non-major clinically relevant bleedings were recorded (rate 3.5 7 100 pt-yrs), 5 were major bleeds (rate 1.2 7 100 pt-yrs), 1 in a patient on aspirin (rate 4.3 7 100 pt-yrs). Bleeding rate was higher in patients on DOACs (crude HR 4.7; 95%CI 1.5\u201315.01). Eight thrombotic events were recorded (rate 1.9 7 100 pt-yrs), 3 recurrent VTE and 5 stroke/TIA. Overall, the incidence of thrombotic events was higher in DOACs patients (crude HR 4.5; 95% CI 1.5; 13.3). The rate of recurrent VTE was similar in the two group. Mortality rate was significantly lower in DOACs patients (crude HR 0.30; 95% CI 0.1;0.9). Conclusion: A higher bleeding risk was found in very elderly VTE patients on DOACs despite the wide use of low-dosages. Similarly a higher thrombotic risk was found while the incidence of recurrent VTE was low and similar between the groups. Mortality rate were significantly lower in DOACs patients

<i>MYH9</i> related disease: four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotype

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. All patients present congenital macrothrombocytopenia and inclusion bodies in neutrophils. Some of them can also develop sensorineural deafness, presenile cataract, and ⁄ or progressive nephropathy leading to end-stage renal failure. We report four families, each with a novel mutation: two missense mutations, in exons 31 and 32, and two out of frame deletions in exon 40. They were associated with no bleeding diathesis, normal, or only slightly reduced platelet count and no extra-hematological manifestations, confirming that alterations of the tail domain cause a mild form of MYH9-RD with no clinically relevant defects

Anticoagulation resumption after intracranial hemorrhage in patients treated with VKA and DOACs

Intracranial hemorrhage (ICH) is associated with severe prognosis and recurrent risk. This impacts on the decision to resume anticoagulation in atrial fibrillation (AF) or venous thromboembolism (VTE) patients. Purpose of our study is to evaluate the incidence rate of recurrent ICH in patients with AF or VTE resuming anticoagulation after a first ICH episode

MYH9 related disease: four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotype

Abstract MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. All patients present congenital macrothrombocytopenia and inclusion bodies in neutrophils. Some of them can also develop sensorineural deafness, presenile cataract, and/or progressive nephropathy leading to end-stage renal failure. We report four families, each with a novel mutation: two missense mutations, in exons 31 and 32, and two out of frame deletions in exon 40. They were associated with no bleeding diathesis, normal, or only slightly reduced platelet count and no extra-hematological manifestations, confirming that alterations of the tail domain cause a mild form of MYH9-RD with no clinically relevant defects

CO2 involved synthesis of quinazoline-2,4(1H,3H)-diones in water using melamine as a thermoregulated catalyst

In this study, pharmaceutically relevant quinazoline-2,4(1H, 3H)-diones were synthesized eco-efficiently by cycloaddition of CO2 and 2-aminobenzonitrile in water, catalyzed by melamine as a thermoregulated catalyst. Quinazoline-2,4(1H, 3H)-dione was produced selectively with 92% yield at 120 degrees C, 4.2 MPa, and automatically separated from the hot catalytic aqueous solution, which was reused directly for several runs until its activity decreased in an obvious manner. Then, the catalyst melamine was recrystallized from the spent aqueous solution via simple cooling and reused for another several catalytic runs. The efficient valorization of CO2 and the straightforward stepwise recovery of the products and catalyst were important to save energy and minimize process waste for the practical industrial production

Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes

Background: Venous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population.Objectives: We aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19-associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses.Methods: This is an observational cohort study, with a prospective cohort of 278 patients with COVID-19-associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age &lt;18 years, other indications to anticoagulant treatment, active cancer, recent (&lt;3 months) major surgery, trauma, pregnancy, and participation in interventional studies. All patients were followed up for a minimum of 12 months after treatment discontinuation. Primary end point was the occurrence of venous and arterial thrombotic events.Results: Patients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P &lt;.001), lower prevalence of chronic inflammatory disease (1.4% and 16.3%, P &lt;.001), and history of VTE (5.0% and 19.0%, P &lt;.001). The median duration of anticoagulant treatment (194 and 225 days, P = 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P = 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4). Conclusion: The risk of recurrent thrombotic events in patients with COVID-19- associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases

Thrombophilia testing in the real-world clinical setting of thrombosis centres taking part in the italian start 2-register

BACKGROUND: Even though it rarely influences venous thromboembolism (VTE) treatment and the fact that it is generally discouraged, thrombophilia testing is still largely prescribed. We assessed: 1) whether/how frequently Italian thrombosis centres requested thrombophilia testing; 2) what results were obtained; and 3) if the results affected treatment and clinical results.MATERIALS AND METHODS: We examined data from 4,826 VTE patients enrolled by 19 clinical centres participating in the START 2-Register.RESULTS: 57.2% of patients were tested. Numbers varied widely among centres (2.9-99.7%). Thrombophilic alterations were recorded in 18.2% of patients and the percentage of positive results was inversely correlated with that of patients tested. Significantly less patients with deep vein thrombosis (DVT) were tested, whereas more were tested when the event was idiopathic, presenting as isolated pulmonary embolism (PE), or in unusual sites. Patients with thrombophilic alterations were younger, more frequently treated with direct oral anticoagulants (DOACs), with lower mortality and less frequently discontinued anticoagulation. DOACs were more frequently prescribed in patients with heterozygous Factor V (FV) Leiden or prothrombin mutations, whereas vitamin K antagonists were preferred in patients with inhibitor deficiencies, combined alterations or antiphospholipid syndrome (APLS). There was no difference in duration of treatment among those with or without alterations, though more APLS patients received an extended treatment course. Bleeding and thrombotic complications occurred with a similar and fairly low incidence in patients with or without thrombophilic alterations.DISCUSSION: Although general testing for thrombophilia in VTE patients is currently discouraged, more than half of the VTE patients included in the START2-Register were tested. However, there were marked differences in practice between Italian thrombosis centres. About 60% of all patients with alterations were treated with DOACs, confirming that DOACs can be a useful option for treatment of thrombophilic VTE patients, with the exclusion of those with APLS

Bleeding and thrombotic complications during treatment with direct oral anticoagulants or vitamin K antagonists in venous thromboembolic patients included in the prospective, observational START2-register

Objective The proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.Design A prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.Setting About 60 Italian anticoagulation and thrombosis centres participated in the observational START2-RegisterParticipants 2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.Interventions Patients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.Outcomes measures Efficacy: rate of VTE recurrence (all thrombotic complications were also recorded). Safety: the rate of major and clinically relevant non-major bleeding events.Results Almost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was &gt;180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14–4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p&lt;0.0001). All-cause mortality was higher in VKA-treated (5.9%) than in DOAC-treated patients (2.6%, p&lt;0.001).Conclusion Italian centres treat most patients with VTE with DOACs and prefer VKA for those with more serious clinical conditions. Recurrences were significantly more frequent in DOAC-treated patients due to increased incidence after 180 days of treatment, probably due to reduced adherence to treatment. These results underline the importance of structured surveillance of DOAC-treated patients with VTE to strengthen treatment adherence during extended therapy

Statins under-treatment and mortality in patients with atrial fibrillation. Insights from the nationwide START registry

Background and aims: Statins are mainstream drugs for cardiovascular (CV) prevention, but under-prescription is an important clinical challenge. Data on the use of single statins and on the rate of under-prescription in atrial fibrillation (AF) are lacking. We evaluated the association of statin underuse with mortality risk in a large AF cohort.Methods and results: As many as 5477 patients from the Italian nationwide START registry were included. The prevalence of different statins was reported and the association of under prescription with all-cause and CV mortality investigated.Mean age was 80.2 years, and 46.4% were women. Among 2899 patients with a clinical indication to statin, only 1578 (54.4%) were on treatment. In a mean follow-up of 22.5 +/- 17.1 months, 491 (4.7%/year) deaths occurred (106 CV deaths, 1.0%/year). Atorvastatin and Simvastatin were inversely associated with all-cause (HR 0.692, 95% CI 0.519-0.923, p = 0.012 and HR 0.598, 95% CI 0.428-0.836, p = 0.003, respectively) and CV death (HR 0.372, 95% CI 0.178-0.776, p = 0.008 and HR 0.306, 95% CI 0.123-0.758, p = 0.010, respectively).The 1321 untreated patients were older, more frequently women and with a higher prevalence of diabetes, previous cerebrovascular disease, peripheral artery disease compared to those on treatment. Statin undertreatment was associated with higher risk of all-cause (HR 1.400, 95% CI 1.078-1.819, p = 0.012) and CV death (HR 2.057, 95% CI 1.188-3.561, p = 0.010).Conclusions: AF patients with an indication to statins but left untreated show a high risk of all-cause and CV mortality. Implementation of statin prescription in the AF population can help reducing the residual mortality risk.(c) 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved