Lower Mortality with Andexanet Alfa vs 4-Factor Prothrombin Complex Concentrate for Factor Xa Inhibitor-Related Major Bleeding in a U.S. Hospital-Based Observational Study

BACKGROUND: Well-designed studies with sufficient sample size comparing andexanet alfa vs 4-factor prothrombin complex concentrate (4F-PCC) in routine clinical practice to evaluate clinical outcomes are limited. OBJECTIVES: To compare in-hospital mortality in patients hospitalized with rivaroxaban- or apixaban-related major bleeding who were treated with andexanet alfa or 4F-PCC. METHODS: An observational cohort study (ClinicalTrials.gov identifier: NCT05548777) was conducted using electronic health records between May 2018 and September 2022 from 354 U.S. hospitals. Inclusion criteria were age ≥18 years, inpatient admission with diagnosis code D68.32 (bleeding due to extrinsic anticoagulation), a record of use of the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa or 4F-PCC treatment during index hospitalization, and a documented discharge disposition. Multivariable logistic regression on in-hospital mortality with andexanet alfa vs 4F-PCC was performed. The robustness of the results was assessed via a supportive propensity score-weighted logistic regression. RESULTS: The analysis included 4395 patients (andexanet alfa, CONCLUSION: In this large observational study, treatment with andexanet alfa in patients hospitalized with rivaroxaban- or apixaban-related major bleeds was associated with 50% lower odds of in-hospital mortality than 4F-PCC. The magnitude of the risk reduction was similar in ICH and GI bleeds

Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA , a multi‐country observational study

Introduction: Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited. Methods: ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included. Discussion: An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization

Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden.</p> <p>Methods</p> <p>All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare.</p> <p>Results</p> <p>Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability.</p> <p>Conclusions</p> <p>There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.</p

Psychotropic drugs among the elderly : Population-based studies on indicators of inappropriate utilisationin relation to socioeconomic determinants and mental disordersEva LesénGothenburg,

Background: Drug utilisation among the elderly is complex due to multiplemorbidities, extensive drug utilisation and an increased sensitivity to drugs. One of the most common drug groups utilised in this population is psychotropic drugs, which include antipsychotics, anxiolytics, hypnotics, and antidepressants. In appropriat eutilisation of drugs among the elderly is an issue of great public health importance. Aims: The overall aim of this thesis is to assess and analyse potentially in appropriat eutilisation of psychotropic drugs among the elderly in Sweden. The specific aims are to assess to what extent the indicator “concurrent use of three or more psychotropic drugs”captures the utilisation of Potentially Inappropriate Psychotropics (PIP) among theelderly, and to analyse potentially inappropriate utilisation of psychotropic drugs inrelation to time, mental disorders, institutionalisation, and socioeconomic determinants among the elderly in Sweden. Methods: Data from individual-based registers on dispensed drugs and socioeconomic determinants in 2006, the Gothenburg 95+ Study (1996-1998), and aggregated drug sales statistics from 2000-2008 were used. The agreement between the two indicators“concurrent use of three or more psychotropic drugs” and PIP was assessed. Utilisationof psychotropic drugs and PIP was assessed in relation to mental disorders and institutionalisation among the 95-year olds, and in relation to socioeconomic determinants among individuals aged 75 years and older. Further, trends over time inutilisation of PIP and recommended drugs were analysed. Results: During 2006, about half of the elderly aged 75 years and older utilised psychotropic drugs and one fifth of all elderly utilised PIP. One fourth of individualsutilising PIP were captured by the indicator “concurrent use of three or morepsychotropic drugs”. In 1996-1998, less than one tenth of the 95-year olds with depression utilised antidepressants, while hypnotics and anxiolytics were more common. Individuals with low income and the non-married were more likely to utilise PIP compared to those with high income and the married, respectively. During 2000-2008, utilisation of PIP decreased and utilisation of recommended psychotropic drugs increased. Conclusions: There are substantial problems in the utilisation of psychotropic drugsamong the elderly. This thesis found that the agreement between two indicators of inappropriate psychotropic drug utilisation was poor, which emphasises the importance of choosing relevant indicators. The findings also show socioeconomic inequities inpsychotropic drug utilisation among the elderly, a low utilisation of antidepressants among 95-year olds diagnosed with depression, and a trend towards the utilisation of recommended rather than inappropriate psychotropic drugs among the elderlyBakgrund: Användning av läkemedel bland äldre är komplicerat på grund avmultisjuklighet, användning av flera läkemedel och en ökad känslighet för läkemedel.En av de vanligaste läkemedelsgrupperna hos äldre är psykofarmaka, som inkluderarantipsykotika, ångestdämpande, sömnmedel och antidepressiva läkemedel. Olämpliganvändning av läkemedel bland äldre är ett betydande folkhälsoproblem. Syfte: Det övergripande syftet med avhandlingen är att beskriva och analyserapotentiellt olämplig användning av psykofarmaka bland äldre i Sverige. De specifikasyftena är att undersöka i vilken utsträckning indikatorn ”samtidig användning av treeller fler psykofarmaka” fångar användningen av potentiellt olämpliga psykofarmaka(PIP) bland äldre och att analysera potentiellt olämplig användning av psykofarmaka irelation till förändring över tid, psykiatriska diagnoser, boendeform och socioekonomiska determinanter bland äldre i Sverige. Metod: Avhandlingen baseras på data från individbaserade register över läkemedelsköp och socioekonomiska determinanter under 2006, Göteborg 95+ studien (1996-1998)samt aggregerade data över läkemedelsförsäljning under 2000-2008. Överensstämmelsen mellan de två indikatorerna ”samtidig användning av tre eller flerpsykofarmaka” och PIP undersöktes. Användning av psykofarmaka och PIP studerades i relation till psykiatriska diagnoser och boendeform hos 95-åringar och i relation till socioekonomiska determinanter hos de som var 75 år och äldre. Vidare analyseradesförändring över tid i användning av PIP och rekommenderade psykofarmaka. Resultat: Hälften av alla äldre som var 75 år och äldre använde psykofarmaka under2006 och en femtedel av alla äldre använde PIP. En fjärdedel av individerna somanvände PIP fångades av indikatorn ”samtidig användning av tre eller flerpsykofarmaka”. Bland 95-åringarna med depression år 1996-1998 använde färre än enav tio antidepressiva läkemedel, medan sömnmedel och ångestdämpande läkemedel varvanligare. PIP var vanligare hos de äldre med låg inkomst och bland de som inte vargifta, jämfört med individer med hög inkomst och de gifta. Under 2000-2008 minskade användningen av PIP medan användningen av rekommenderade psykofarmaka ökade. Slutsatser: Det finns fortfarande stora problem i äldres användning av psykofarmaka.Avhandlingen visar en låg överensstämmelse mellan två indikatorer för olämpliganvändning av psykofarmaka, vilket pekar på betydelsen av att välja relevantaindikatorer. Avhandlingen visar också på socioekonomiska ojämlikheter i användningenav psykofarmaka hos äldre, en låg användning av antidepressiva läkemedel bland 95-åringar med depression och en ökning i användningen av rekommenderade istället förolämpliga psykofarmaka bland äldr

Refill adherence in relation to substitution and the use of multiple medications : A nationwide population based study on new ACE-inhibitor users

Objective: Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. Study Design and Setting: New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. Results: The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. Conclusion: The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications

Age in relation to comorbidity and outcome in patients with high-risk TIA or minor ischemic stroke : A Swedish national observational study

Introduction: Recent trials report positive results for preventing vascular events with dual antiplatelet therapy (DAPT) in patients with high-risk TIA or minor ischemic stroke. We aimed to investigate this population regarding influence of age on vascular risk factors, hospital stay and mortality. Patients and methods: Data on patients aged 40-100 years with TIA or ischemic stroke in the Swedish Stroke Register during 2012-13 were linked with national registers. To identify patients with high-risk TIA (ABCD(2) &gt;= 6) or minor ischemic stroke (NIHSS &lt;= 5) eligible for DAPT, we excluded patients with atrial fibrillation, anticoagulant use, prior major bleeding, or unknown stroke severity. Findings: We identified 10,053 potential DAPT-candidates (mean age 72.6 years, 45.2% female, 16.4% with TIA). With advancing age, most vascular risk factors increased. Antiplatelet treatment increased from 31.9% before the event to 95.5% after discharge. Within 1 year following index event, the proportion of patients with &gt;= 1 re-admission increased with age (29.2% in 40-64 year-olds; 47.2% in 85-100 year-olds). All-cause death per 100 person-years was 6.9 (95% CI 6.4-7.4) within 1 year, and highest in the first 30 days (15.2; 95% CI 12.8-18.2). For each year of increased age, the risk of death increased with 3.5% (p = 0.128) in patients 40-64 years and with 11.8% (p &lt; 0.001) in those &gt;= 85 years. Conclusions: While in theory representing a subset of patients with mild injury, our observational study highlights substantial use of health-care resources and high mortality rates among patients with high-risk TIA or minor ischemic stroke assumed eligible for DAPT