{"id":6274,"date":"2026-10-19T09:48:42","date_gmt":"2026-10-19T09:48:42","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-laeknavisindum-arnar-bragi-ingason\/"},"modified":"2026-10-19T09:48:42","modified_gmt":"2026-10-19T09:48:42","slug":"doktorsvorn-i-laeknavisindum-arnar-bragi-ingason","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-laeknavisindum-arnar-bragi-ingason\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00e6knav\u00edsindum – Arnar Bragi Ingason"},"content":{"rendered":"
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F\u00f6studaginn 27. ma\u00ed ver Arnar Bragi Ingason doktorsritger\u00f0 s\u00edna \u00ed l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Samanbur\u00f0ur \u00e1 virkni, \u00f6ryggi og me\u00f0fer\u00f0arheldni bl\u00f3\u00f0\u00feynningarlyfja um munn. Comparison of the efficacy, safety, and adherence of oral anticoagulants.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Don C. Rockey, pr\u00f3fessor og yfirma\u00f0ur vi\u00f0 Medical University of South Carolina, og dr. Sam Schulman, pr\u00f3fessor vi\u00f0 McMaster University \u00ed Hamilton, Ontario, Kanada.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var Einar Stef\u00e1n Bj\u00f6rnsson pr\u00f3fessor og me\u00f0lei\u00f0beinandi var J\u00f3hann P\u00e1ll Hreinsson. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Ingvar Bjarnason, pr\u00f3fessor, Karl K. Andersen, pr\u00f3fessor, P\u00e1ll Torfi \u00d6nundarson, pr\u00f3fessor og Sigr\u00fan Helga Lund, t\u00f6lfr\u00e6\u00f0ingur.<\/p>\n

\u00de\u00f3rarinn Gu\u00f0j\u00f3nsson, pr\u00f3fessor og deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

V\u00f6rninni ver\u00f0ur streymt:\u00a0\u00a0https:\/\/livestream.com\/hi\/doktorsvornarnarbragiingason<\/a><\/p>\n

\u00c1grip<\/strong><\/p>\n

Bl\u00f3\u00f0\u00feynningarlyf um munn eru me\u00f0al algengustu upp\u00e1skrifu\u00f0u lyfja \u00e1 he\u00edmsv\u00edsu. V\u00edtam\u00edn K-hemlar, eins og warfar\u00edn, voru einu bl\u00f3\u00f0\u00feynningarlyfin um munn \u00ed meira en 60 \u00e1r e\u00f0a \u00fear til beinir storkuhemlar komu \u00e1 marka\u00f0 \u00e1 \u00e1runum 2009-2013. Beinir storkuhemlar hindra bl\u00f3\u00f0storku me\u00f0 \u00fev\u00ed a\u00f0 hemja anna\u00f0hvort bl\u00f3\u00f0storku\u00fe\u00e1tt II (dabigatran) e\u00f0a X (apixaban, edoxaban og rivaroxaban). Ni\u00f0urst\u00f6\u00f0ur upphaflegra slembira\u00f0a\u00f0ra ranns\u00f3kna s\u00fdndu a\u00f0 beinir storkuhemlar voru tengdir vi\u00f0 svipa\u00f0a t\u00ed\u00f0ni bl\u00f3\u00f0sega og l\u00e6gri t\u00ed\u00f0ni st\u00f3rv\u00e6gra bl\u00e6\u00f0inga samanbori\u00f0 vi\u00f0 warfar\u00edn. \u00cd framhaldinu hefur veri\u00f0 m\u00e6lt me\u00f0 notkun beinna storkuhemla sem fyrstu me\u00f0fer\u00f0ar hj\u00e1 sj\u00faklingum me\u00f0 g\u00e1ttatif e\u00f0a bl\u00e1\u00e6\u00f0asega. Engar slembira\u00f0a\u00f0ar ranns\u00f3knir bera \u00fe\u00f3 beina storkuhemla innbyr\u00f0is og fyrri \u00e1horfsranns\u00f3knir hafa haft mikilv\u00e6gar takmarkanir. Auk \u00feess eru til takm\u00f6rku\u00f0 g\u00f6gn um samanbur\u00f0 \u00e1 t\u00ed\u00f0ni efri og ne\u00f0ri meltingarvegsbl\u00e6\u00f0inga og nefbl\u00e6\u00f0inga milli bl\u00f3\u00f0\u00feynningarlyfja um munn. A\u00f0 sama skapi er enn \u00f3lj\u00f3st hvort me\u00f0fer\u00f0arheldni s\u00e9 fr\u00e1brug\u00f0in milli warfar\u00edns og beinna storkuhemla.<\/p>\n

Markmi\u00f0 verkefnisins var a\u00f0 bera saman virkni, \u00f6ryggi og me\u00f0fer\u00f0arheldni mismunandi bl\u00f3\u00f0\u00feynningarlyfja um munn. Markmi\u00f0 greinar I var a\u00f0 bera saman t\u00ed\u00f0ni bl\u00f3\u00f0sega og st\u00f3rv\u00e6gra bl\u00e6\u00f0inga milli beinna storkuhemla. Markmi\u00f0 greinar II var a\u00f0 bera saman t\u00ed\u00f0ni meltingarv\u00e6gsbl\u00e6\u00f0inga milli beinna storkuhemla. Markmi\u00f0 greinar III var a\u00f0 bera saman t\u00ed\u00f0ni efri og ne\u00f0ri meltingarvegsbl\u00e6\u00f0inga milli warfar\u00edns og beinna storkuhemla. Markmi\u00f0 greinar IV var a\u00f0 bera saman t\u00ed\u00f0ni nefbl\u00e6\u00f0inga milli warfar\u00edns og beinna storkuhemla. A\u00f0 lokum var markmi\u00f0 greinar V a\u00f0 bera saman me\u00f0fer\u00f0arheldni milli mismunandi bl\u00f3\u00f0\u00feynningarlyfja um munn.<\/p>\n

Ranns\u00f3knargagnagrunnur var b\u00fainn til sem innih\u00e9lt uppl\u00fdsingar um alla sj\u00faklinga \u00e1 \u00cdslandi sem fylltu \u00fat bl\u00f3\u00f0\u00feynningarlyf um munn \u00e1 t\u00edmabilinu 1. mars 2014 til 28. febr\u00faar 2019. Gagnagrunnurinn samanst\u00f3\u00f0 af uppl\u00fdsingum fr\u00e1 lyfjagagnagrunni Landl\u00e6knis, d\u00e1narmeinaskr\u00e1, rafr\u00e6num gagnagrunnum Landsp\u00edtalans, fj\u00f3r\u00f0ungssj\u00fakrah\u00fasunum \u00e1 Akranesi, Akureyri, \u00cdsafir\u00f0i, Neskaupsta\u00f0 og heilsug\u00e6slum v\u00ed\u00f0s vegar um landi\u00f0. \u00d6ll bl\u00f3\u00f0sega- og bl\u00e6\u00f0ingartilfelli voru sta\u00f0fest handvirkt me\u00f0 \u00fev\u00ed a\u00f0 fara inn \u00ed sj\u00fakraskr\u00e1r sj\u00faklinga. Ranns\u00f3knar\u00fe\u00fd\u00f0i\u00f0 samanst\u00f3\u00f0 af \u00f6llum sj\u00faklingum sem h\u00f3fu me\u00f0fer\u00f0 me\u00f0 apixaban, dabigatran, rivaroxaban og warfarin \u00e1 ranns\u00f3knart\u00edmabilinu. L\u00edkindaskorsvigtun var notu\u00f0 til a\u00f0 f\u00e1 samanbur\u00f0arh\u00e6fa h\u00f3pa. Bl\u00e6\u00f0ingar- og bl\u00f3\u00f0segat\u00ed\u00f0ni var borin saman me\u00f0 Cox a\u00f0hvarfsgreiningu og Kaplan-Meier lifunarmati. L\u00e9leg me\u00f0fer\u00f0arheldni var skilgreind sem hlutfall daga \u00e1 me\u00f0fer\u00f0 undir 80%. Logist\u00edsk a\u00f0hvarfsgreining var notu\u00f0 til a\u00f0 bera saman hlutfall sj\u00faklinga me\u00f0 l\u00e9lega me\u00f0fer\u00f0arheldni milli lyfja. Logist\u00edsk a\u00f0hvarfsgreining var einnig notu\u00f0 til a\u00f0 meta sj\u00faklinga\u00fe\u00e6tti tengda l\u00e9legri me\u00f0fer\u00f0arheldni.<\/p>\n

Rivaroxaban var tengt vi\u00f0 l\u00e6gri t\u00ed\u00f0ni bl\u00f3\u00f0sega og hjartadreps samanbori\u00f0 vi\u00f0 dabigatran. \u00c1 sama h\u00e1tt var apixaban tengt vi\u00f0 l\u00e6gri t\u00ed\u00f0ni hjartadreps samanbori\u00f0 vi\u00f0 dabigatran en s\u00e1 samanbur\u00f0ur hafna\u00f0i \u00fe\u00f3 ekki n\u00falltilg\u00e1tunni. Rivaroxaban var tengt vi\u00f0 aukna t\u00ed\u00f0ni st\u00f3rv\u00e6gra bl\u00e6\u00f0inga, kl\u00edn\u00edskt mikilv\u00e6gra meltingarvegsbl\u00e6\u00f0inga og kl\u00edn\u00edskt mikilv\u00e6gra nefbl\u00e6\u00f0inga samanbori\u00f0 vi\u00f0 a\u00f0ra beina storkuhemla. T\u00ed\u00f0ni heilabl\u00f3\u00f0falla og heildard\u00e1nart\u00ed\u00f0ni var svipu\u00f0 milli mismunandi beinna storkuhemla. Warfar\u00edn var tengt vi\u00f0 aukna t\u00ed\u00f0ni efri en ekki ne\u00f0ri meltingarvegsbl\u00e6\u00f0inga samanbori\u00f0 vi\u00f0 beina storkuhemla. Warfar\u00edn var einnig tengt vi\u00f0 h\u00e6rri nefbl\u00e6\u00f0ingart\u00ed\u00f0ni en beinir storkuhemlar. Dabigatran var tengt vi\u00f0 auknar l\u00edkur \u00e1 l\u00e9legri me\u00f0fer\u00f0arheldni samanbori\u00f0 vi\u00f0 apixaban, rivaroxaban og warfar\u00edn. Me\u00f0fer\u00f0arheldni var svipu\u00f0 hj\u00e1 sj\u00faklingum \u00e1 apixaban, rivaroxaban og warfar\u00edn. Kvenkyn, h\u00e1\u00fer\u00fdstingur, saga um heilabl\u00f3\u00f0fall\/heilabl\u00e6\u00f0ingu og samhli\u00f0a notkun \u00e1 stat\u00ednum voru \u00f6ll tengd vi\u00f0 aukna h\u00e6ttu \u00e1 l\u00e9legri me\u00f0fer\u00f0arheldni.\u00a0<\/p>\n

English abstract<\/strong><\/p>\n

Oral anticoagulants (OACs) are among the most commonly used medication worldwide. Vitamin K antagonists, such as warfarin, were the only available oral anticoagulants for over 60 years. However, in the 2010s, novel direct oral anticoagulants (DOACs) were approved that act by directly inhibiting either factor II (dabigatran) or factor X (apixaban, edoxaban, and rivaroxaban). The results of the initial randomized controlled trials demonstrated that DOACs were associated with similar thromboembolic rates and lower major bleeding rates compared to warfarin. As a result, DOACs are currently considered first line therapy for patients with atrial fibrillation and venous thromboembolism. However, randomized controlled trials comparing DOACs head-to-head are currently lacking, and previous observational studies have important limitations. Additionally, data are largely lacking on other outcomes such as rates of upper and lower gastrointestinal bleeding (GIB) and epistaxis event rates. Similarly, it is still unknown whether medication adherence differs between warfarin and DOACs.<\/p>\n

The aims of this thesis were to compare the efficacy, safety, and adherence of different oral anticoagulants. Specifically, the aim of paper I was to compare rates of thromboembolism and major bleeding between different DOACs, the aim of paper II was to compare rates of any clinically relevant GIB between DOACs, the aim of paper III was to compare rates of upper and lower GIB between warfarin and DOACs, the aim of paper IV was to compare rates of epistaxis between warfarin and DOACs, and the aims of paper V was to compare the likelihood of nonadherence between different OACs.<\/p>\n

A study outcome database was created that included all patients in Iceland who filled a prescription for an OAC from 1 March 2014 to 28 February 2019. The database combined data from the Icelandic Medicine Registry; the electronic healthcare databases of Landspitali University Hospital and the regional hospitals of Akranes, Akureyri, \u00cdsafj\u00f6r\u00f0ur, and Neskaupsta\u00f0ur; the electronic healthcare databases of the primary healthcare centers around the country; and the Icelandic death registry. All thromboembolic and major bleeding events were manually verified by chart review. The study population included new users of apixaban, dabigatran, rivaroxaban, and warfarin (for papers III-V). Inverse probability weighting was used to yield balanced study groups and bleeding and thromboembolic events were compared using Cox regression and Kaplan-Meier survival estimates. Nonadherence, defined as proportion of days covered below 80%, was compared between groups using logistic regression. Similarly, logistic regression was used to estimate patient characteristics associated with nonadherence.<\/p>\n

Rivaroxaban was associated with lower rates of any thromboembolism and myocardial infarction (MI) compared to dabigatran. Similarly, apixaban was associated with lower rates of MI compared to dabigatran, although this comparison did not reject the null hypothesis. Meanwhile, rivaroxaban was associated with higher rates of any major bleeding, any clinically relevant GIB, and any clinically relevant epistaxis compared to apixaban and dabigatran. Rates of stroke and all-cause mortality were similar between all DOAC users. Warfarin was associated with higher rates of upper but not lower or overall GIB compared to DOACs. Warfarin was also associated with higher epistaxis rates compared to DOACs. Dabigatran was associated with higher nonadherence compared to apixaban, rivaroxaban, and warfarin. Meanwhile, the likelihood of nonadherence was similar between apixaban, rivaroxaban, and warfarin. Apart from OAC type, female gender, hypertension, history of cerebrovascular accident, and concomitant statin use were all associated with lower likelihood of nonadherence.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Arnar Bragi Ingason er f\u00e6ddur \u00e1ri\u00f0 1992 \u00ed Reykjav\u00edk. Hann lauk st\u00fadentspr\u00f3fi af n\u00e1tt\u00farufr\u00e6\u00f0ibraut fr\u00e1 Menntask\u00f3lanum \u00ed Reykjav\u00edk \u00e1ri\u00f0 2013. Hann lauk bakkal\u00e1rsgr\u00e1\u00f0u \u00ed l\u00e6knisfr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands 2016 og emb\u00e6ttispr\u00f3fi \u00ed l\u00e6knisfr\u00e6\u00f0i fr\u00e1 sama sk\u00f3la 2019. Samhli\u00f0a doktorsn\u00e1minu lauk Arnar kand\u00eddats\u00e1ri og vann eitt \u00e1r sem s\u00e9rn\u00e1msl\u00e6knir \u00ed skur\u00f0l\u00e6kningum vi\u00f0 Landsp\u00edtalann. Arnar mun hefja s\u00e9rn\u00e1m \u00ed almennum skur\u00f0l\u00e6kningum vi\u00f0 University of Vermont \u00ed j\u00fan\u00ed n\u00e6stkomandi. Foreldrar Arnars eru Ingi Valt\u00fdsson og Brynd\u00eds Bragad\u00f3ttir. Maki Arnars er Bj\u00f6rk Gu\u00f0mundsd\u00f3ttir leikkona.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5129,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2022-05-27T13:00:00+00:00","_phd_date_end":"2022-05-27T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Samanbur\u00f0ur \u00e1 virkni, \u00f6ryggi og me\u00f0fer\u00f0arheldni bl\u00f3\u00f0\u00feynningarlyfja um munn. 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