Benefit–Risk of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness: Pooled Analysis From MAGELLAN and MARINER

Background Thromboprophylaxis extended after hospital discharge in medically ill patients currently is not recommended by practice guidelines because of uncertainty about the benefit for preventing major or fatal thromboembolic events, and the risk of bleeding. Methods and Results We assessed the benefit and risk of thromboprophylaxis with rivaroxaban 10 mg once daily extended for 25 to 45 days after hospitalization for preventing major thromboembolism in medically ill patients using the pooled data in 16 496 patients from 2 randomized trials, MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post‐Discharge Venous Thrombo‐Embolism Risk) and MAGELLAN (Multicenter, randomized, parallel‐group efficacy and safety study for the prevention of venous thromboembolism in hospitalized medically ill patients comparing rivaroxaban with enoxaparin). The data from the MARINER trial were pooled with the data from the MAGELLAN trial in patients who were free of thrombotic or bleeding events up to the last dose of enoxaparin/placebo and who continued in the outpatient phase of thromboprophylaxis. The composite outcome of major thromboembolic events (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, myocardial infarction, and nonhemorrhagic stroke) and all‐cause mortality was used to assess benefit and was compared with the risk of the composite of fatal and critical site bleeding. The incidence of the composite efficacy outcome was 1.80% (148 of 8222 patients) in the rivaroxaban group, compared with 2.31% (191 of 8274 patients in the placebo group) (HR, 0.78 [95% CI, 0.63–0.97], P =0.024). Fatal or critical site bleeding events were infrequent and occurred in <0.1% of patients in both groups (rivaroxaban 0.09%; placebo 0.04%; HR, 2.36; P =0.214). Conclusions The results suggest a benefit for reducing major thromboembolic outcomes (number needed to treat: 197), with a favorable trade‐off to fatal or critical site bleeding (number needed to harm: 2045). Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT00571649 and NCT02111564.

Sickle Cell Disease and Cystic Fibrosis Are Associated with Increased Non-Administration of VTE Prophylaxis in Adult Patients

Background: Sickle cell disease (SCD) and cystic fibrosis (CF) are associated with an increased risk of venous thromboembolism (VTE). VTE prophylaxis non-administration is a risk factor for VTE. Since many patients with SCD or CF experience frequent hospitalizations, we hypothesized that missed doses of VTE prophylaxis may be common in these populations. The purpose of this study was to characterize VTE prophylaxis non-administration among patients with SCD or CF compared to medically ill patients without SCD or CF. Methods: We conducted a single-center retrospective cohort study of patient admissions from July 1 st, 2016 to December 31 st, 2019 who were prescribed at least 2 doses of pharmacologic VTE prophylaxis. Three adult inpatient cohorts were defined: patients with SCD, patients with CF, and medically ill patients without SCD or CF. We excluded patients on pediatric and surgical units, and excluded doses received while in intensive care units or prescribed as once doses. The primary outcome was the proportion of missed doses of VTE prophylaxis by cohort. Secondary outcomes included the proportion of patients who missed at least one dose by cohort, the proportion of missed doses by medication and frequency, and the proportion of missed doses in patients with more than one admission during the study period. Multivariable logistic regression was used to identify characteristics associated with non-administration. Results: The 13,316 subjects included 246 with SCD, 89 with CF, and 12,981 medically ill. Subjects with SCD and CF were younger than medically ill patients [median (IQR) age 31 (16) and 30 (11) years, respectively versus 58 (24) years, p&lt;0.01]. A higher number of SCD and CF patients had multiple hospital admissions than medically ill patients (52.5% and 73.0%, respectively vs. 21.8%, p&lt;0.01). VTE prophylaxis dose non-administration overall and by prescribed regimen are shown in Table 1. During the study period, 95,697 doses were prescribed; 32.7% were not administered in the SCD cohort, 61.8% in the CF cohort, and 19.7% in the medically ill cohort (p&lt;0.01). In the multivariable logistic regression, SCD diagnosis [odds ratio (OR) 1.73, 95% confidence interval (CI) 1.29-2.32], CF diagnosis (OR 4.64, 95% CI 2.98-7.21), age &lt; 30 years (OR 2.29, 95% CI 1.98-2.63), and multiple admissions (OR 1.13, 95% CI 1.01-1.26) were associated with non-administration of one or more doses. Black race (OR 0.86, 95% CI 0.78-0.95) and receiving a once daily prophylaxis regimen (OR 0.76, 95% CI 0.69-0.84) were associated with reduced odds of missing a dose. Patients with SCD, patients with CF, and younger patients missed greater proportions of their individually prescribed doses (Table 2). Conclusion: Patients with SCD or CF missed a larger proportion of pharmacologic VTE prophylaxis compared to medically ill patients. Factors independently associated with increased odds of non-administration include age &lt; 30 years and multiple hospital admissions. Black race and once daily administration were associated with decreased odds of non-administration. These findings suggest that targeted education or once-daily dosing may improve VTE prevention in high-risk lifelong disorders such as SCD and CF. Figure 1 Figure 1. Disclosures Naik: Rigel: Research Funding. Lanzkron: GBT: Research Funding; Shire: Research Funding; Novo Nordisk: Consultancy; Teva: Current holder of individual stocks in a privately-held company; Pfizer: Current holder of individual stocks in a privately-held company; Imara: Research Funding; CSL Behring: Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy. Dane: Sanofi Genzyme: Honoraria; Janssen: Honoraria; Alexion: Honoraria.

Multimorbidity, psychoactive substance use and psychological distress among acute medically ill patients: a cross-sectional study

BackgroundIn order to target the complex health needs of patients with multimorbidity using psychoactive substances, knowledge regarding the association between substance use and multimorbidity in an acute setting is needed.AimsExamine psychoactive substance use patterns among acute medically ill patients, and determine the association between multimorbidity and substance use, and psychological distress.DesignCross-sectional study.Setting and participants2874 acute medically ill patients admitted to a medical emergency department in Oslo, Norway.MeasurementsPrimary outcome: multimorbidity recorded by the presence of ≥2 International Classification of Diseases 10th revision—physical and/or mental health conditions per patient, extracted from medical records. Predictor variables: self-reported data on age, sex, occupational status, psychological distress (Hopkins Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4) and results from blood samples on psychoactive medicinal and illicit drugs.FindingsOf all patients, 57.2% had multimorbidity. Of these, 62.6% reported psychological distress, 85.5% consumed either alcohol, medicinal and/or illicit drugs and 64.4% combined alcohol with psychoactive medicinal drugs. Patients with risky alcohol use were more likely to have multimorbidity compared with patients with low-risk alcohol use (OR 1.53; 95% CI 1.05 to 2.24). Patients using psychoactive medicinal drugs were more likely to have multimorbidity compared with non-users (OR 1.34; 95% CI 1.07 to 1.67).ConclusionMultimorbidity was associated with psychoactive medicinal drug and risky alcohol use, and psychological distress. Substance use was widespread, with alcohol and psychoactive medicinal drugs most frequently combined. Monitoring substance use among multimorbid patients is necessary to develop tailored treatments, and reduce burden on the healthcare system.