Background The IMPROVE score is a validated venous thromboembolism (VTE) assessment tool to risk stratify hospitalized, medically ill patients based on clinical variables. It was hypothesized that addition of D-dimer measurement to derive a new IMPROVEDD score would improve identification of at risk of VTE. Methods The association of the IMPROVE score and D-dimer ≥ 2 × the upper limit of normal (ULN) with the risk of symptomatic deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was evaluated in 7,441 hospitalized, medically ill patients randomized in the APEX trial. Based on the Cox regression analysis, the IMPROVEDD score was derived by adding two points to the IMPROVE score if the D-dimer was ≥ 2 × ULN. Results Baseline D-dimer was independently associated with symptomatic VTE through 77 days (adjusted HR: 2.22 [95% CI: 1.38–1.58], p = 0.001). Incorporation of D-dimer into the IMPROVE score improved VTE risk discrimination (ΔAUC: 0.06 [95% CI: 0.02–0.09], p = 0.0006) and reclassification (continuous NRI: 0.34 [95% CI: 0.17–0.51], p = 0.001; categorical NRI: 0.13 [95% CI: 0.03–0.23], p = 0.0159). Patients with an IMPROVEDD score of ≥2 had a greater VTE risk compared with those with an IMPROVEDD score of 0 to 1 (HR: 2.73 [95% CI: 1.52–4.90], p = 0.0007). Conclusion Incorporation of D-dimer into the IMPROVE VTE risk assessment model further improves risk stratification in hospitalized, medically ill patients who received thromboprophylaxis. An IMPROVEDD score of ≥2 identifies hospitalized, medically ill patients with a heightened risk for VTE through 77 days.

D-Dimer is a biomarker of fibrin formation and degradation. While a d-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated d-dimer with adverse outcomes has received far less emphasis. An elevated d-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated d-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the d-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

Background: Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. Methods: A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. Results: A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I² = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I² = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I² = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I² = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). Conclusions: The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets.

Background: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y ₁₂ inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. Methods: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y ₁₂ inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. Results: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66–0.94; P =0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62–0.90; P =0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [ P =0.032 versus group 3], group 2=8.0% [ P =0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [ P =0.001 versus group 3], group 2=21.7% [ P =0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. Conclusions: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y ₁₂ inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01830543.