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3. Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study.

Author

Lehto, Mika, Luojus, Alex, Halminen, Olli, Haukka, Jari, Putaala, Jukka, Linna, Miika, Mustonen, Pirjo, Kinnunen, Janne, Lehtonen, Ossi, Teppo, Konsta, Tiili, Paula, Kouki, Elis, Itäinen-Strömberg, Saga, Niemi, Mikko, Aro, Aapo L., Hartikainen, Juha, and Juhani Airaksinen, K. E.

Subjects
ORAL medication, ATRIAL fibrillation, ISCHEMIC stroke, WARFARIN, SAFETY standards
Abstract

Background: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Objective: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. Materials and methods: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). Results: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. Conclusions: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

Author

Itäinen-Strömberg, Saga, Lehto, Mika, Halminen, Olli, Putaala, Jukka, Haukka, Jari, Lehtonen, Ossi, Teppo, Konsta, Mustonen, Pirjo, Linna, Miika, Hartikainen, Juha, Airaksinen, Kari Eino Juhani, and Aro, Aapo L

Abstract

Aims Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. Methods and results This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42–1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. Conclusion The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Association of income and educational levels with adherence to direct oral anticoagulant therapy in patients with incident atrial fibrillation

Author

Teppo, Konsta, Jaakkola, Jussi, Biancari, Fausto, Halminen, Olli, Linna, Miika, Haukka, Jari, Putaala, Jukka, Tiili, Paula, Lehtonen, Ossi, Niemi, Mikko, Mustonen, Pirjo, Kinnunen, Janne, Hartikainen, Juha, Airaksinen, K. E.Juhani, Lehto, Mika, University of Turku, University of Helsinki, Department of Industrial Engineering and Management, Dept Signal Process and Acoust, Turku University Hospital, University of Eastern Finland, Aalto-yliopisto, and Aalto University

Subjects
socioeconomic status, educational level, income, atrial fibrillation, adherence, persistence, direct oral anticoagulants
Abstract

Funding Information: Konsta Teppo: none. Jussi Jaakkola: none. Fausto Biancari: none Olli Halminen: none. Jukka Putaala: Dr. Putaala reports personal fees from Boehringer‐Ingelheim, personal fees and other from Bayer, grants and personal fees from BMS‐Pfizer, personal fees from Portola, other from Amgen, personal fees from Herantis Pharma, personal fees from Terve Media, other from Vital Signum, personal fees from Abbott, outside the submitted work. Pirjo Mustonen: Consultant: Roche, BMS‐Pfizer‐alliance, Novartis Finland, Boehringer Ingelheim, MSD Finland. Jari Haukka: Consultant: Research Janssen R&D; Speaker: Bayer Finland. Miika Linna: Speaker: BMSPfizer‐alliance, Bayer, Boehringer‐Ingelheim. Juha Hartikainen: Research grants: The Finnish Foundation for Cardiovascular Research, EU Horizon 2020, EU FP7. Advisory Board Member: BMS‐Pfizer‐alliance, Novo Nordisk, Amgen. Speaker: Cardiome, Bayer. K. E. Juhani Airaksinen: Research grants: The Finnish Foundation for Cardiovascular Research; Speaker: Bayer, Pfizer and Boehringer‐Ingelheim. Member in the advisory boards: Bayer, Pfizer and AstraZeneca. Mika Lehto: Consultant: BMS‐Pfizer‐alliance, Bayer, Boehringer‐Ingelheim, and MSD; Speaker: BMS‐Pfizer‐alliance, Bayer, Boehringer Ingelheim, MSD, Terve Media and Orion Pharma. Research grants: Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund, Boehringer‐Ingelheim. Paula Tiili: none. Mikko Niemi: none: Ossi Lehtonen: none. Funding Information: This work was supported by the Aarne Koskelo Foundation, The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund (TYH2019309). /: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Role of the Funder Sponsor Publisher Copyright: © 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. Low socioeconomic status has been associated with poor outcomes in patients with atrial fibrillation (AF). However, little is known about socioeconomic disparities in adherence to stroke prevention with direct oral anticoagulants (DOACs). We assessed the hypothesis that AF patients with higher income or educational levels have better adherence to DOACs in terms of treatment implementation and persistence. The used nationwide registry-based FinACAF cohort covers all patients with incident AF starting DOACs in Finland during 2011–2018. The implementation analyses included 74 222 (mean age 72.7 ± 10.5 years, 50.8% female) patients, and persistence analyses included 67 503 (mean age 75.3 ± 8.9 years, 53.6% female) patients with indication for permanent anticoagulation (CHA2DS2-VASc score >1 in men and >2 in women). Patients were divided into income quartiles and into three categories based on their educational attainment. Therapy implementation was measured using the medication possession ratio (MPR), and patients with MPR ≥0.90 were defined adherent. Persistence was measured as the incidence of therapy discontinuation, defined as the first 135-day period without DOAC purchases after drug initiation. Patients with higher income or education were consistently more likely adherent to DOACs in the implementation phase (comparing the highest income or educational category to the lowest: adjusted odds ratios 1.18 (1.12–1.25) and 1.21 (1.15–1.27), respectively). No association with income or educational levels was observed on the incidence of therapy discontinuation. In conclusion, we observed that income and educational levels both have independent positive association on the implementation of DOAC therapy but no association on therapy persistence in patients with AF.

Published
2022

7. Association of income and educational levels with adherence to direct oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study

Author

Teppo, Konsta, primary, Jaakkola, Jussi, additional, Biancari, Fausto, additional, Halminen, Olli, additional, Linna, Miika, additional, Haukka, Jari, additional, Putaala, Jukka, additional, Tiili, Paula, additional, Lehtonen, Ossi, additional, Niemi, Mikko, additional, Mustonen, Pirjo, additional, Kinnunen, Janne, additional, Hartikainen, Juha, additional, Airaksinen, K. E. Juhani, additional, and Lehto, Mika, additional

Published
2022
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8. Medical ultrasound imaging using sparse arrays

Author

Rajamäki, Robin, Perustieteiden korkeakoulu, Koivunen, Visa, Lehtonen, Ossi, Rajamäki, Robin, Perustieteiden korkeakoulu, Koivunen, Visa, and Lehtonen, Ossi

Abstract

Sensor arrays and spatial signal processing are used in a variety of applications ranging from radar and wireless communications to radio astronomy and medical imaging. In order to achieve high spatial resolution, a large number of sensors with a regular geometry is typically needed. The number of sensors and consequently the hardware costs can be significantly reduced while maintaining resolution by using sparse array configurations. In medical ultrasound imaging, the cost of scanners can be reduced by using fewer sensors, or a higher resolution can be achieved with an equal number of sensors. In active sensing, sparse sensor arrays can match the imaging performance of uniform arrays in the far field by utilizing the co-array, a virtual array determined by array geometry and imaging mode. In the near field and with wideband transmission, such as in medical ultrasound, the co-array becomes spatially varying, which needs to be compensated for by the imaging method. Instead of using a large number of sensors with regular geometry, sparse arrays may acquire multiple component images that are combined. The component images are obtained by using and receive element weights calculated for different directions and distances in the near field. In this work, complex image addition in the near field is evaluated in simulated ultrasound imaging implemented with Field II, a program for simulating ultrasound transducer fields using linear acoustics. The near field weights provide a significant improvement over using far field weights in near field imaging. Several linear sparse array configurations are compared, including the Minimum-Redundancy Array. The configurations achieve similar resolution and contrast for array apertures typically used in medical ultrasound, evaluated with the full width of a point target at half of maximum intensity and contras-to-noise ratio respectively. Only small differences were found in the number of component images required by different array ar, Anturiryhmiä ja spatiaalisia signaalinkäsittelymenetelmiä käytetään lukuisissa sovelluskohteissa, aina tutkista ja langattomasta viestinnästä radioastronomiaan ja lääketieteelliseen kuvantamiseen. Tavallisesti korkean paikkaresoluution saavuttamiseen tarvitaan suuri määrä antureita säännöllisessä muodostelmassa. Sensorien määrää ja sitä kautta laitekustannuksia voidaan vähentää käyttämällä harvoja anturiryhmiä ilman että resoluutio kärsii. Lääketieteellisessä kuvantamisessa ultraääniskannerien kustannuksia voidaan laskea käyttämällä vähemmän antureita, tai suurempi resoluutio voidaan saavuttaa samalla anturimäärällä. Aktiivisen kuvantamisen sovelluksissa harvat anturiryhmät voivat kaukokentässä saavuttaa samat kuvantamisominaisuudet kuin vastaava tasavälinen hyödyntäen virtuaalista anturiryhmää. Tämän virtuaalisen anturisarjan määrittää fyysisen anturisarjan geometria ja käytetty kuvantamismuoto. Lähikentässä ja laajakaistaisia signaaleja käytettäessä, kuten esimerkiksi lääketieteellisessä ultraäänikuvantamisessa, virtuaaliryhmä muuttuu paikasta riippuvaksi, mitä kuvantamismenetelmän täytyy kompensoida. Harva anturiryhmä ei voi hyödyntää suurta määrää säännöllisesti sijoitettuja sensoreita, ja sen sijaan kuva voidaan koostaa summaamalla yhteen useampi komponenttikuva. Nämä komponenttikuvat saadaan käyttämällä suunta- ja etäisyyskohtaisesti laskettuja lähetys- ja vastaanottopainokertoimia. Tässä työssä lähikentän komponenttikuvien summausmenetelmää arvioidaan simuloidulla ultraäänikuvantamisella. Simulaatiot toteutettu Field II -ohjelmalla, joka simuloi ultraäänianturien painekenttiä käyttäen lineaarista akustiikkaa. Lähikenttäpainokertoimet tuovat selvän parannuksen verrattuna kaukokenttäkerrointen käyttöön lähikentässä. Työssä vertaillaan useampaa lineaarista harvaa anturimallia, mukaan lukien redundanssin minimoiva anturiryhmä. Ultraäänikuvantamiselle tyypillisillä apertuureilla eri anturiryhmät saavuttivat samankaltaisen resoluution ja kontrastin, joita arvioitii

Published
2021

9. Surface-relief gratings in halogen-bonded polymer-azobenzene complexes

Author

Stumpel, Jelle E., Saccone, Marco, DIchiarante, Valentina, Lehtonen, Ossi, Virkki, Matti, Metrangolo, Pierangelo, Priimagi, Arri, Department of Applied Physics, Tampere University of Technology, Polytechnic University of Milan, Aalto-yliopisto, and Aalto University

Subjects
Azobenzene, Supramolecular, Halogen bonding, Photoresponsive, Surface-relief grating
Abstract

In recent years, supramolecular complexes comprising a poly(4-vinylpyridine) backbone and azobenzene-based halogen bond donors have emerged as a promising class of materials for the inscription of light-induced surface-relief gratings (SRGs). The studies up to date have focused on building supramolecular hierarchies, i.e., optimizing the polymer-azobenzene noncovalent interaction for efficient surface patterning. They have been conducted using systems with relatively low azobenzene content, and little is known about the concentration dependence of SRG formation in halogen-bonded polymer-azobenzene complexes. Herein, we bridge this gap, and study the concentration dependence of SRG formation using two halogen-bond-donating azobenzene derivatives, one functionalized with a tetrafluoroiodophenyl and the other with an iodoethynylphenyl group. Both have been previously identified as efficient molecules in driving the SRG formation. We cover a broad concentration range, starting from 10 mol % azobenzene content andgoing all the way up to equimolar degree of complexation. The complexes are studied as spin-coated thin films, and analyzed by optical microscopy, atomic force microscopy, and optical diffraction arising during the SRG formation. We obtained diffraction efficiencies as high as 35%, and modulation depths close to 400 nm, which are significantly higher than the values previously reported for halogen-bonded polymer-azobenzene complexes.

Published
2017

11. Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

Author

Itäinen-Strömberg S, Lehto M, Halminen O, Putaala J, Haukka J, Lehtonen O, Teppo K, Mustonen P, Linna M, Hartikainen J, Airaksinen KEJ, and Aro AL

Subjects
Humans, Male, Female, Aged, Middle Aged, Finland epidemiology, Risk Factors, Warfarin adverse effects, Warfarin therapeutic use, Risk Assessment, Time Factors, Atrial Fibrillation epidemiology, Atrial Fibrillation drug therapy, Electric Countershock adverse effects, Thromboembolism etiology, Thromboembolism prevention & control, Thromboembolism epidemiology, Anticoagulants therapeutic use, Anticoagulants adverse effects, Hemorrhage epidemiology, Hemorrhage chemically induced, Hemorrhage etiology, Registries
Abstract

Aims: Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population., Methods and Results: This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred., Conclusion: The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications., Competing Interests: Conflict of interest: S.I.-S.: research grants: Finnish Foundation for Cardiovascular Research, Einar och Karin Stroems Foundation, and Otto A. Malmin Foundation. M.Le.: consulting fees: BMS-Pfizer Alliance, Bayer, Boehringer Ingelheim, and MSD; speaker: BMS-Pfizer Alliance, Bayer, Boehringer Ingelheim, MSD; supporting of meetings and/or travel: BMS-Pfizer Alliance, Bayer, Boehringer Ingelheim, and MSD; and advisory board: BMS-Pfizer Alliance, Bayer, Boehringer Ingelheim, and MSD. J.P.: research grants: Helsinki and Uusimaa Hospital District, Academy of Finland, The Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation, Bayer, and Amgen; speaker: Bayer, Boehringer Ingelheim, BMS-Pfizer, and Abbott; advisory board: Novo Nordisk and Herantis Pharma; visiting editor: Terve Media; and stock ownership: Vital Signum. Ju.H.: research grants: The Finnish Foundation for Cardiovascular Research and EU Horizon 2020, EU FP7; advisory board member: BMS-Pfizer Alliance and Novo Nordisk; and speaker: Novo Nordisk. K.E.J.A.: research grants: The Finnish Foundation for Cardiovascular Research; and speaker: Bayer, Pfizer, and Boehringer Ingelheim. A.L.A.: research grants: Finnish Foundation for Cardiovascular Research and Sigrid Juselius Foundation. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2024
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