Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients

Background Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), warfarin, direct factor Xa inhibitors, clopidogrel, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 209,208 (55.9%) were on at least one study drug. The three most common study drugs were ACEI 97,872 (26.1%), ARB 83,329 (22.3%) and clopidogrel 38,203 (10.2%). Current users of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel were associated with reduced risk of getting COVID-19 (3-13%), and reduced risk of dying after a COVID-19 diagnosis (8-19%). Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. Conclusions Maintenance use of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel was associated with reduction in risk of acquiring COVID-19 and dying from it.

Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers

Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract

Who are studying at International Branch Campuses in China? A case study

International Branch Campuses (IBCs) grow rapidly, and China is the largest host country of IBCs. This article examines the student characteristics at an IBC in China. The student characteristics arise from the literature regarding college choice and the choice of IBC. A documentary study examines the academic performance, represented by gaokao scores, of the students from an IBC with independent legal person status in China. Further, using the data of 798 survey respondents, the student characteristics are analyzed with a descriptive analysis, and the results are compared to the data in existent documents and reports. The results show that the development of IBCs in China favors urban and socioeconomically advantaged students. Family income becomes a stronger and direct factor on the choice of IBC. Chinese middle- and upper-class utilize their capitals to obtain study opportunities at IBCs. This article fills the gap in the student characteristics and identifies the inequalities at an IBC. The implications are discussed.

Laboratory assessment of the compliance to direct oral anticoagulants

Введение. Для пролонгированной профилактики тромбозов после операций, при фибрилляции предсердий, терапии тромбозов глубоких вен и/или тромбоэмболии легочной артерии широко используются прямые пероральные антикоагулянтные препараты (ПОАК). Считается, что ПОАК лишены недостатков, присущих антагонистам витамина К (АВК) и обладают предсказуемыми фармакокинетическими и фармакодинамическими эффектами и следовательно не требуют рутинного лабораторного контроля для коррекции и подбора дозы препарата. Отдельного внимания, на наш взгляд, заслуживает вопрос приверженности к терапии ПОАК. Цель исследования: оценка приверженности к терапии прямыми пероральными ингибиторами фактора Ха путем определения концентрации ПОАК в плазме крови пациентов. Материалы и методы. Выполнено проспективное клинико-лабораторное исследование, включены 50 пациентов с продленной антитромботической терапией ПОАК. Для оценки приверженности к терапии проведено определение пиковой концентрации прямых ингибиторов фактора Ха хромогенным методом. Результаты. До 10% пациентов в реальной клинической практике не принимали назначенную антитромботическую терапию и скрыли этот факт от врача. Таким образом, с помощью определения концентрации прямых ингибиторов фактора Ха хромогенным методом можно выявить отсутствие приверженности к терапии ПОАК. Заключение. Для определения приверженности к антикоагулянтной терапии прямыми ингибиторами фактора Ха возможно использование метода оценки концентрации ПОАК в плазме крови, что позволяет оценить приверженность пациента к данному виду терапии и, как следствие, эффективность и безопасность продленной антитромботической терапии. Background. For prolonged prophylaxis of thrombosis after surgery, of atrial fibrillation, therapy of deep vein thrombosis and/or pulmonary embolism, direct oral anticoagulants (DOACs) are widely used. It is believed that DOACs lack the deficiencies inherent in antagonists of vitamin K (AVK), have predictable pharmacokinetic and pharmacodynamic effects, and therefore do notrequire routine laboratory monitoring to adjust and select the dose of the drug. We pay special attention to the issue of adherence to DOACs therapy. Objectives: to assess compliance to therapy with direct oral factor Xa inhibitors by determining plasma DOACs concentration. Patients/Methods. A prospective clinical and laboratory study was performed, 50 patients with prolonged antithrombotic therapy by DOACs were included. To assess compliance to therapy, the peak concentration of direct factor Xa inhibitors was determined by the chromogenic method. Results. In real clinical practice up to 10% of patients did not take the prescribed antithrombotic therapy and hid this fact from the doctor. Thus, by determining the concentration of direct factor Xa inhibitors by the chromogenic method, it is possible to identify a lack of compliance to therapy. Conclusions. Determination of plasma DOACs concentration allows assessing the patient’s adherence to anticoagulant therapy with direct factor Xa inhibitors and the efficacy and safety of prolonged antithrombotic therapy.