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Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.
Goette, A, Eckardt, L, Valgimigli, M, Lewalter, T, Laeis, P, Reimitz, PE, Smolnik, R, Zierhut, W, Tijssen, JG, Vranckx, P
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(6):831-840
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AIMS: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome. METHODS Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis. RESULTS Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024). CONCLUSION After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
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Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation.
Mostaza, JM, Suarez, C, Cepeda, JM, Manzano, L, Sánchez, D, ,
BMC cardiovascular disorders. 2021;(1):384
Abstract
BACKGROUND This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. METHODS A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). RESULTS A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. CONCLUSIONS This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation.
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Comparison of Anticoagulation Quality between Acenocoumarol and Warfarin in Patients with Mechanical Prosthetic Heart Valves: Insights from the Nationwide PLECTRUM Study.
Menichelli, D, Poli, D, Antonucci, E, Cammisotto, V, Testa, S, Pignatelli, P, Palareti, G, Pastori, D, The Italian Federation Of Anticoagulation Clinics Fcsa,
Molecules (Basel, Switzerland). 2021;(5)
Abstract
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
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Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial.
Engelter, ST, Traenka, C, Gensicke, H, Schaedelin, SA, Luft, AR, Simonetti, BG, Fischer, U, Michel, P, Sirimarco, G, Kägi, G, et al
The Lancet. Neurology. 2021;(5):341-350
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BACKGROUND Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. METHODS We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. FINDINGS Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. INTERPRETATION Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
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Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs.
Turcato, G, Zaboli, A, Pfeifer, N, Maccagnani, A, Tenci, A, Giudiceandrea, A, Zannoni, M, Ricci, G, Bonora, A, Brigo, F
The American journal of emergency medicine. 2021;:388-393
Abstract
BACKGROUND Although the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED). AIM: To determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI. METHODS Patients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables. RESULTS Among the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery. CONCLUSIONS The machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.
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Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants.
Capiau, A, Mehuys, E, Van Tongelen, I, Christiaens, T, De Sutter, A, Steurbaut, S, Moudallel, S, Rydant, S, Vrijens, B, de Backer, TLM, et al
Heart (British Cardiac Society). 2020;(22):1740-1746
Abstract
OBJECTIVE This study aimed to assess implementation adherence (how well the patient's actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users. METHODS A cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ). RESULTS A total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3-4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8-99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns. CONCLUSIONS Our data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients' thromboembolic risk and NOACs' short half-lives, further optimisation of NOAC use seems warranted in this population.
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Health-related quality of life in nonvalvular atrial fibrillation patients with controlled or uncontrolled anticoagulation status.
Varona, JF, Seguí-Ripoll, JM, Lozano-Duran, C, Cuadrado-Gómez, LM, Montagud-Moncho, JB, Ramos-Guerrero, A, Mirete-Ferrer, JC, Donado, E, García-Alegría, J, ,
Health and quality of life outcomes. 2020;(1):383
Abstract
BACKGROUND There is a dearth of evidence regarding Health-Related Quality of Life (HRQoL) in nonvalvular atrial fibrillation (NVAF) patients undergoing oral anticoagulation therapy. Our objective was to describe HRQoL in NVAF patients on oral anticoagulation, focusing on uncontrolled patients on vitamin K antagonists (VKAs) versus controlled patients on VKAs or non-vitamin K antagonist oral anticoagulants (NOACs), in a real-world setting. Additionally, we assessed the clinical characteristics of patients with uncontrolled anticoagulation. METHODS An observational, multicentre, and cross-sectional study, enrolling 38 Spanish Hospitals' Internal Medicine Departments. HRQoL was assessed using the validated Spanish version of the Sawicki questionnaire. High self-perceived HRQoL was indicated by high scores in the general treatment satisfaction and self-efficacy dimensions, and by low scores in the strained social network, daily hassles and distress dimensions. RESULTS Five hundred and one patients were included for assessment. Mean scores ± SD were closer to a high perceived HRQoL in controlled than uncontrolled patients for the five dimensions of the questionnaire: 4.9 ± 1.0 versus 3.6 ± 1.3 for general treatment satisfaction; 4.3 ± 1.0 versus 3.6 ± 1.0 for self-efficacy, 3.1 ± 0.9 versus 3.9 ± 1.1 for strained social network, 2.1 ± 0.8 versus 3.0 ± 1.0 for daily hassles and 1.8 ± 0.9 versus 2.6 ± 1.2 for distress. CONCLUSIONS HRQoL in patients with controlled anticoagulant status treated with NOACs or VKAs was better than in patients with uncontrolled anticoagulant status. This seems to indicate that anticoagulation control status influences perception of HRQoL, highlighting the importance of its evaluation when assessing HRQoL in NVAF patients.
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Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.
Male, C, Lensing, AWA, Palumbo, JS, Kumar, R, Nurmeev, I, Hege, K, Bonnet, D, Connor, P, Hooimeijer, HL, Torres, M, et al
The Lancet. Haematology. 2020;(1):e18-e27
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BACKGROUND Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING Bayer AG and Janssen Research & Development.
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Extent of arterial calcification by conventional vitamin K antagonist treatment.
Hasific, S, Øvrehus, KA, Gerke, O, Hallas, J, Busk, M, Lambrechtsen, J, Urbonaviciene, G, Sand, NPR, Nielsen, JS, Diederichsen, L, et al
PloS one. 2020;(10):e0241450
Abstract
BACKGROUND AND AIMS Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). METHODS We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates. RESULTS The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category. CONCLUSIONS Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category.
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Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study.
Anguita Sánchez, M, Bertomeu Martínez, V, Ruiz Ortiz, M, Cequier Fillat, Á, Roldán Rabadán, I, Muñiz García, J, Badimón Maestro, L, Esteve Pastor, MA, Marín Ortuño, F, ,
Revista espanola de cardiologia (English ed.). 2020;(1):14-20
Abstract
INTRODUCTION AND OBJECTIVES To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. METHODS The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. RESULTS A total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. CONCLUSIONS Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.