Comparison of the effectiveness and safety of direct oral anticoagulants: nationwide propensity score-weighted study

Peer reviewe

Comparison of medication adherence to different oral anticoagulants : population-based cohort study

Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE: Previous observational studies have yielded conflicting results on whether medication adherence differs between patients receiving warfarin and direct oral anticoagulants (DOACs). Importantly, no study has adequately accounted for warfarin dosing being continuously modified based on INR values while dosing of DOACs is fixed. We aimed to compare non-adherence between new users of apixaban, dabigatran, rivaroxaban and warfarin in a population-based cohort. METHODS: New users of apixaban, dabigatran, rivaroxaban and warfarin from 2014 to 2019 living in the Icelandic capital area were included. Non-adherence was defined as proportion of days covered below 80%. Inverse probability weighting was used to yield balanced study groups and non-adherence was compared using logistic regression. Factors associated with non-adherence were estimated using multivariable logistic regression. RESULTS: Overall, 1266 patients received apixaban, 247 dabigatran, 1566 rivaroxaban and 768 warfarin. The proportion of patients with non-adherence ranged from 10.5% to 16.7%. Dabigatran was associated with significantly higher odds of non-adherence compared with apixaban (OR 1.57, 95% CI 1.21 to 2.04, p<0.001), rivaroxaban (OR 1.45, 95% CI 1.12 to 1.89, p=0.005) and warfarin (OR 1.63, 95% CI 1.23 to 2.15, p<0.001). The odds of non-adherence were similar for apixaban, rivaroxaban and warfarin. Apart from the type of oral anticoagulants (OACs) used, female sex, hypertension, history of cerebrovascular accident and concomitant statin use were all independently associated with lower odds of non-adherence. CONCLUSION: Dabigatran was associated with higher odds of non-adherence compared with other OACs. Non-adherence was similar between apixaban, rivaroxaban and warfarin users. Female sex and higher comorbidity were associated with better medication adherence.Peer reviewe

Samanburður á virkni, öryggi og meðferðarheldni blóðþynningarlyfja um munn

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, rivaroxaban, and edoxaban). 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. The aims of this thesis were to compare the efficacy, safety, and adherence of different oral anticoagulants. Therefore, 5 studies were designed and are presented in 5 distinct papers. 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. 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, Ísafjörður, and Neskaupsstaður; 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. Kaplan-Meier curves were used to visualize the data. 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. 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 patients receiving different DOACs. 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 odds 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 odds of nonadherence. In summary, rivaroxaban was associated with higher rates of bleeding compared to other DOACs but lower rates of any thromboembolism and MI compared to dabigatran. Warfarin was associated with high rates of upper GIB and epistaxis compared to DOACs. Dabigatran was associated with poorer adherence than other oral anticoagulants.RANNÍS (207113-051

Cardiomyocyte Migration in Mammalian Heart Regeneration

Verkefni var unnið við hjartaskurðdeildina í Stanford Unversity School of Medicine.Inngangur: Þrátt fyrir að endurnýjun hjartans í nýfæddum músum hafi verið nýlega rannsakað er enn óljóst hvernig skrið hjartavöðvafruma til blóðtappasvæðis fer fram eftir brottnám hjartabrodds. Sýnt hefur verið að endurnýjun hjartans er háð bæði ígöngu makrófaga og nýæðamyndunar. Enn fremur hefur rannsókn á endurnýjun úttaugar sýnt að eftir að settaug er klippt í tvennt berast makrófagar í bilið og örva nýæðamyndun í bilinu. Schwann frumur skríða svo eftir þessum æðum og brúa bilið milli klipptu endanna. Við settum því fram þá tilgátu að skrið hjartavöðvafruma fylgi svipuðu ferli eftir brottnám hjartabrodds. Aðferðir: Eins dags gamlar mýs voru annað hvort meðhöndlaðar með hjartabroddsbrottnámi eða sham aðgerð. Mótefnalitanir voru síðan gerðar á mismunandi tímapunktum til þess að skoða skrið æðaþels- og hjartavöðvafruma til blóðtappasvæðis. Til þess að meta hvort hjartavöðvafrumur skríða eftir æðaþeli var svokölluð transwell migration assay framkvæmd þar sem hjartavöðvafrumur og mennskar naflastrengsbláæðaþelsfrumur voru ræktaðar saman og myndir teknar á smásjá á tíu mínútna fresti yfir 12 klst tímabil. Niðurstöður: Niðurstöður sýndu að blóðæðar bárust inn í blóðtappasvæði á undan hjartavöðvafrumum. Meirihluti útskota skríðandi hjartavöðvafruma var auk þess í nálægð við blóðæðar í blóðtappasvæði. Loks lágu flestar hjartavöðvafrumur samhliða æðaþelsneti þegar frumutegundirnar tvær voru ræktaðar saman. Ályktanir: Nálægð skríðandi hjartavöðvafruma og blóðæða in vivo og in vitro bendir til þess að sterkt samband sé milli frumutegundanna tveggja. Frekari rannsóknir þarf hins vegar til þess að meta hvort æðaþelsfrumur séu nauðsynlegar og nægjanlegar til þess að stýra skriði hjartavöðvafruma

Opioid overdose following voriconazole treatment - case report

Publisher Copyright: © 2019 Laeknafelag Islands. All rights reserved.67 ára gömul kona, sem tók langverkandi ópíóíðalyf (oxýkódon) vegna langvarandi brjóstverkja, varð fyrir bráðri ópíóíðaeitrun eftir að hafin var meðferð með vórikónazóli. Vórikónazól er sveppalyf sem getur bælt virkni CYP3A4 sem er niðurbrotsensím í lifur og gegnir lykilhlutverki í umbroti ýmissa lyfja. Í þessu tilfelli jókst sermisstyrkur oxýkódons sem olli alvarlegri ópíóíðaeitrun. 67-year-old female who was taking oxycodone due to chronic chest pain suffered from opioid overdose after starting treatment with voriconazole. Voriconazole is an antifungal that inhibits CYP3A4 activity in the liver. In the case reported herein, this led to higher plasma concentration of oxycodone which caused severe opioid overdose.Peer reviewe

Opioid overdose following voriconazole treatment – case report

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download67 ára gömul kona, sem tók langverkandi ópíóíðalyf (oxýkódon) vegna langvarandi brjóstverkja, varð fyrir bráðri ópíóíðaeitrun eftir að hafin var meðferð með vórikónazóli. Vórikónazól er sveppalyf sem getur bælt virkni CYP3A4 sem er niðurbrotsensím í lifur og gegnir lykilhlutverki í umbroti ýmissa lyfja. Í þessu tilfelli jókst sermisstyrkur oxýkódons sem olli alvarlegri ópíóíðaeitrun.67-year-old female who was taking oxycodone due to chronic chest pain suffered from opioid overdose after starting treatment with voriconazole. Voriconazole is an antifungal that inhibits CYP3A4 activity in the liver. In the case reported herein, this led to higher plasma concentration of oxycodone which caused severe opioid overdos