Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19.

Importance: Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives: To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants: A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures: Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures: The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results: A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance: In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

COVID-19 and Risk of VTE in Ethnically Diverse Populations.

BACKGROUND: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking. RESEARCH QUESTION: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19? STUDY DESIGN AND METHODS: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19. RESULTS: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/µL. INTERPRETATION: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.