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

Blæðingar frá meltingarvegi: Nýgengi, orsakir, tengsl lyfja og horfur.

Gastrointestinal bleeding (GIB) is a common reason for hospitalization and referral to endoscopy. Certain drugs seem to be associated with GIB, although their role in specific types of GIB and etiology is unclear. The outcome of patients with GIB seems to be favourable although long-term follow-up data is lacking. The aim of this thesis was to evaluate the incidence of gastrointestinal bleeding as well as to describe its etiology. Furthermore, to study the association of GIB and various drugs potentially associated with GIB and to determine the short- and long-term outcome in GIB patients. Lastly, to examine what proportion of patients with colorectal cancer have bleeding-related symptoms and what characterizes those patients. The total cohort of the thesis included all patients that underwent endoscopy at the National University Hospital of Iceland in 2010 and all of those who underwent colonoscopy in 2013 at the National University Hospital of Iceland. The indications and results of endoscopies were prospectively noted. Endoscopic nurses interviewed patients on drug history prior to endoscopy. Furthermore, drug history was obtained by reviewing medical records and by access to a nationwide pharmaceutical database. Patients were further divided to 4 main cohorts: patients with acute upper gastrointestinal bleeding (AUGIB) in 2010, patients with acute lower gastrointestinal bleeding (ALGIB) in 2010, patients with ALGIB in both 2010 and 2013 and lastly, patients with unexplained GIB in 2010. Patients with unexplained bleeding were further categorized to patients with: unexplained overt GIB, unexplained occult GIB, obscure GIB and clinical suspicion of bleeding. Unexplained bleeders were retrospectively followed-up for at least three years. Controls were selected from patients undergoing endoscopy in the same period and matched for gender and age (±5 years). In addition, all patients diagnosed with colorectal cancer in Iceland from 2008-2011 were identified via the Icelandic Cancer Registry and their medical records retrospectively reviewed with respect to bleeding-related symptoms. The most common etiologies of AUGIB were peptic ulcer (40%), Mallory-Weiss tears (12%) and oesophagitis (10%). The incidence of AUGIB was 87/100,000 inhabitants per year in the greater metropolitan area of Reykjavik, increasing with age. The following drugs were associated with AUGIB, non-steroidal anti-inflammatory drugs (NSAIDs) (p = 0.0002), low-dose aspirin (LDA) (p = 0.0371) and warfarin (p = 0.0069). NSAID use was associated with clinically significant AUGIB (Odds ratio – OR 6.6). The need for acute surgery in AUGIB was low (1.9%) and the rate of AUGIB-related deaths was very low (1.3%). The most common etiologies of ALGIB were diverticulosis (23%), ischemic colitis (16%) and inflammatory-bowel disease (12%). The incidence for ALGIB was also 87/100,000 inhabitants per year in the greater metropolitan area of Reykjavik, increasing with age. The use of NSAIDs, LDA and warfarin as well as concomitant use of LDA and warfarin was associated with ALGIB, odds ratio (OR) 3.5, 1.5, 2.8 and 3.6, respectively. Furthermore, bleeding from diverticulosis was associated with NSAIDs (OR 8.8), LDA (OR 2.0) and warfarin (OR 2.7). Ischemic colitis was associated with LDA (OR 2.3) and IBD with NSAIDs (OR 3.4). Patients with clinically significant ALGIB were more likely than bleeders without clinically significant bleeding to be using NSAIDs, warfarin and combined therapy of LDA and warfarin, OR 2.0, 2.5 and 30.7, respectively. No patient underwent acute surgery for ALGIB and the rate of ALGIB-related deaths was very low (1.2%). Of patients with unexplained bleeding, the incidence of obscure GIB was 10/100,000 inhabitants per year. The use of NSAIDs or warfarin was associated with both unexplained overt GIB and unexplained occult GIB, OR 2.0 and OR 2.0 for NSAID use, respectively, OR 3.9 and OR 4.5 for warfarin use, respectively. Only 1.6% of patients with unexplained occult bleeding were diagnosed with new/missed colorectal cancer in a mean follow-up of 3.0 years. Patients with unexplained overt and unexplained occult GIB were not more likely than controls to have another bleeding episode during a follow-up of at least three years, 5%, 6% and 3.5% respectively. Of patients diagnosed with colorectal cancer, 74% had bleeding-related symptoms, of those 61% had overt symptoms. Patients with bleeding-related symptoms were less likely than non-bleeders to have metastases at diagnosis (OR 0.56). Warfarin was associated with overt bleeding symptoms when compared to controls, OR 3.2. However, LDA use was not associated with bleeding-related symptoms. Acute gastrointestinal bleeding is common, while obscure GIB is rare. The use of NSAIDs, LDA and warfarin seem to play an important role in gastrointestinal bleeding throughout the gastrointestinal tract and may increase risk of clinically significant bleeding. The short-term outcome of patients wi

Samanburður spágetu lógistískrar aðhvarfsgreiningar og stigulmögnunar fyrir útkomu einstaklinga með blæðingu frá neðri hluta meltingarvegar

Inngangur: Skortur er á spálíkönum sem spá fyrir um hvaða sjúklingar með blæðingu frá neðri hluta meltingarvegar munu ekki þurfa meðferð á spítala. Markmið: Að þróa slíkt spálíkan með lógistískri aðhvarfsgreiningu og stigulmögnun, einnig að bera saman þessar tvær tölfræðiaðferðir. Aðferðir: Aftursýn, þýðisbundin rannsókn sem tók til þeirra sem komu á bráðamóttöku vegna blæðingar frá neðri hluta meltingarvegar 2010-2013. Meðferð á spítala var skilgreind sem blóðgjöf, meðferð með speglunartæki, stíflun á slagæð eða skurðaðgerð. Þýði var skipt upp í þjálfunargögn (70%) og prófgögn (30%). Þjálfunargögnin voru notuð til þess að þjálfa líkönin, prófgögnin til þess að gilda líkönin og kanna mátgæði þeirra. Niðurstöður: Í heildina voru 581 sjúklingur sem kom á bráðamóttöku í 625 skipti vegna blæðingar, meðalaldur 61 ár (±22), karlar 49%. Af sjúklingum í þjálfunargögnum voru 72% sem þurftu ekki á meðferð á spítala að halda. Marktækir spáþættir lógistískrar aðhvarfsgreiningar voru slagbilsþrýstingur ≥100mmHg (líkindahlutfall [LH] 4,9; 95% öryggisbil [ÖB] 1,2-21), blóðrauði >120g/L (LH 103; 95%ÖB 42-385), blóðrauði 105-120g/L (LH 19; 95%ÖB 7.4-53), engin blóðflöguhamlandi lyf (LH 3,7; 95%ÖB 2,0-7,1), engin blóðþynningarlyf (LH 2,2; 95%ÖB 0,96-5,1), púls ≤100 (LH 2,9; 95%ÖB 1,3-6,7), og engin blæðing á bráðamóttöku (LH 3,8; 95%ÖB 2,0-7,3). Mikilvægustu breytur stigulmögnunar voru blóðrauði, slagbilsþrýstingur, púls og blæðing á bráðamóttöku. Gilding líkana á prófgögnum: Neikvætt forspárgildi 96% (95%ÖB 91-99%) fyrir lógistíska aðhvarfsgreiningu og flatarmál undir ferli 0,83, sömu gildi fyrir stigulmögnun voru 97% (92-99%) og 0,82. Ályktun: Við höfum hannað nýtt spálíkan fyrir sjúklinga með blæðingu frá neðri hluta meltingarvegar, spágeta lógistískrar aðhvarfsgreiningar og stigulmögnunar var svipuð.Background: Risk scores that identify which patients with lower gastrointestinal bleeding (LGIB) do not require hospital-based intervention are lacking. Aims: To develop such a score with logistic regression (LR) and gradient boosting (GB), furthermore, to compare the two methods. Methods: A retrospective, population-based study including patients presenting to the emergency room (ER) with LGIB from 2010-2013. Hospital-based intervention was defined as blood transfusion, endoscopic hemostasis, arterial embolization or surgery. The cohort was split into train (70%) and test (30%) data. Train data were used to train the models and the test data used to validate them. Results: Overall, 581 patients presented 625 times to the ER, mean age 61 (±22), males 49%. Of train data patients, 72% did not require hospital-based intervention. Independent predictors of no hospital-based intervention in LR were systolic pressure ≥100mmHg (Odds ratio [OR] 4.9; 95% confidence interval [CI] 1.2-21), hemoglobin >12g/dL (OR 103; 95%CI 42-285), hemoglobin 10.5-12.0g/dL (OR 19; 7.4-53), no antiplatelets (OR 3.7; 95%CI 2.0-7.1), no anticoagulants (OR 2.2; 95%CI 0.96-5.1), pulse ≤100 (OR 2.9; 95%CI 1.3-6.7), and no visible bleeding in ER (OR 3.8; 95%CI 2,0-7,3). The most important predictors in GB were hemoglobin, systolic pressure, pulse and no visible bleeding in ER. Validation on the test data showed a negative predictive value and area-under-curve of 96% (95%CI 91-99%) and 0,83 for LR compared to 97% (92-99%) and 0,82 for GB, respectively. Conclusions: A new risk score has been developed for LGIB, the predictive ability of LR and GB were similar in this context

Blæðingar frá meltingarvegi á Landspítala 2010. Orsakir og horfur

Inngangur: Bráðar blæðingar frá efri og neðri hluta meltingarvegar eru algeng ástæða innlagna á Landspítala en hingað til hafa ekki verið til neinar tölur hér á landi um tíðni og orsakir blæðinga frá meltingarvegi á ári. Markmið verkefnisins voru að kanna orsakir blæðinga og hversu stór hluti þessara sjúklinga eru meðhöndlaðir gegnum maga- eða ristilspeglun og hve árangursrík sú meðferð er. Að sama skapi kanna hversu margir þurfa að gangast undir skurðaðgerð til að stoppa blæðingar af þessu tagi. Einnig að kanna þátt blóðþynnandi lyfja sem og NSAID (bólgueyðandi lyf sem ekki eru sterar) í blæðingu og/eða meinmyndun. Efni og aðferðir: Rannsóknin er framsýn og úrtakið telur allar maga- eða ristilspeglanir sem framkvæmdar voru á LSH frá 1. janúar 2010 til 31. desember 2010. Ábendingar og niðurstöður speglunar voru skráðar niður af viðkomandi meltingarlækni og hjúkrunarfræðingar á speglunardeild tóku niður lyfjasögu sjúklings. Farið var í gegnum sjúkraskrá þeirra sjúklinga sem greindir voru með blæðingu eða grun um hana. Ábendingar, lyf og niðurstöður voru svo sannreyndar. Niðurstöður: Speglanir á LSH voru 3347 og einstaklingar sem fóru í speglun töldu 2481. Af þeim voru 559 (22,5%) með blæðingu frá meltingarvegi og þar af 234 (41,9%) frá efri hluta meltingarvegar og 325 (58,1%) frá neðri hluta meltingarvegar. Af þessum 2481 voru 350 (14,1%) tilfelli þar sem að óljóst var um hvort blæðingu var að ræða eður ei. Nýgengi blæðingar frá efri hluta meltingarvegar var 155/100.000 og nýgengi blæðinga frá neðri hluta meltingarvegar var 189/100.000. Einstaklingar á aldrinum 18-59 töldu um 45% blæðinga á meðan sjúklingar 60 ára og eldri töldu 55%. Kynjahlutfall var 53,5% karlar og 46,5% konur. Helstu niðurstöður magaspeglunar voru skeifugarnarsár, 17,1%, og magasár, 16,2%. Helstu niðurstöður ristilspeglunar voru krabbamein, 15,1%, og ristilpokar (diverticulosa) 13,5%. Af öllum 234 tilfellum blæðingar frá efri hluta meltingarvegar var skurðaðgerð framkvæmd vegna blæðingar þrisvar sinnum (1,3%). Dauðsföll af völdum blæðingar frá efri meltingarvegi voru tvö (0,36%), annað vegna nekrótískrar magaslímhúðar og afbrigðileika í blóðstorknun, hitt vegna samspil blæðandi magasárs og hjartaáfalls. Af öllum 325 blæðingum frá neðri hluta meltingarvegar var eitt dauðsfall, þá hafði krabbamein í blöðruhálskirtli vaxið inn í ristil sem orsakaði blæðingu sem ekki var hægt að stöðva. Fleiri sjúklingar voru meðhöndlaðir með NSAID (p=0,006), hjartamagnýl (p=0,0007), kóvar (p=0,034) og NSAID + hjartamagnýl (p=0,0001) á meðal þeirra sem voru með blæðandi maga- og eða skeifugarnarsár (n=93) miðað við samanburðarhóp (n=186). Ályktun: Nýgengi blæðinga frá meltingarvegi er hátt á Íslandi. Langflesta sjúklinga er hægt að meðhöndla með lyfjum eða með speglunartæki á framgangsríkan hátt. Horfur eru almennt góðar og skurðaðgerðir og dauðsföll vegna blæðingar eru fátíð. NSAID og blóðþynnandi lyf virðast eiga þátt í blæðandi maga-og skeifugarnarsárum

Hepatitis due to Epstein-Barr virus and cytomegalovirus: clinical features and outcomes.

To access publisher's full text version of this article click on the hyperlink belowTo determine the frequency of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes.A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006-2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records.Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain-Barré syndrome following the infection.A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis

Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

To access publisher's full text version of this article click on the hyperlink belowBackground: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited. Objective: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban. Design: Nationwide population-based cohort study. Setting: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland. Patients: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Measurements: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression. Results: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses. Limitations: Unmeasured confounding and small subgroup analyses. Conclusion: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.Icelandic Centre for Research Landspitali University Hospital Research Fun