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Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

ABSTRACT: Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

SUBMITTER: Meizlish ML

PROVIDER: S-EPMC8013588 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAspirin use in COPD has been associated with reduced all-cause mortality in meta-regression analysis with few equivocal studies. However, the effect of aspirin on COPD morbidity is unknown.MethodsSelf-reported daily aspirin use was obtained at baseline from SPIROMICS participants with COPD (FEV1/FVC < 70%). Acute exacerbations of COPD (AECOPD) were prospectively ascertained through quarterly structured telephone questionnaires up to 3 years and categorized as moderate (symptoms treated with antibiotics or oral corticosteroids) or severe (requiring ED visit or hospitalization). Aspirin users were matched one-to-one with nonusers, based on propensity score. The association of aspirin use with total, moderate, and severe AECOPD was investigated using zero-inflated negative binomial models. Linear or logistic regression was used to investigate the association with baseline respiratory symptoms, quality of life, and exercise tolerance.ResultsAmong 1,698 participants, 45% reported daily aspirin use at baseline. Propensity score matching resulted in 503 participant pairs. Aspirin users had a lower incidence rate of total AECOPD (adjusted incidence rate ratio [IRR], 0.78; 95% CI, 0.65-0.94), with similar effect for moderate but not severe AECOPD (IRR, 0.86; 95% CI, 0.63-1.18). Aspirin use was associated with lower total St. George's Respiratory Questionnaire score (β, -2.2; 95% CI, -4.1 to -0.4), reduced odds of moderate-severe dyspnea (modified Medical Research Council questionnaire score ≥ 2; adjusted odds ratio, 0.69; 95% CI, 0.51-0.93), and COPD Assessment Test score (β, -1.1; 95% CI, -1.9 to -0.2) but not 6-min walk distance (β, 0.7 m; 95% CI, -14.3 to 15.6).ConclusionsDaily aspirin use is associated with reduced rate of COPD exacerbations, less dyspnea, and better quality of life. Randomized clinical trials of aspirin use in COPD are warranted to account for unmeasured and residual confounding.Trial registryClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov.

Project description:BackgroundHospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients.MethodsWe retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts.ResultsThe analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345-0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110-1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114-3.729, p = 0.016).ConclusionEmpiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

Project description:Objective: Examine the possible beneficial effects of early, D-dimer driven anticoagulation in preventing thrombotic complications and improving the overall outcomes of COVID-19 intubated patients. Methods: To address COVID-19 hypercoagulability, we developed a clinical protocol to escalate anticoagulation based on serum D-dimer levels. We retrospectively reviewed all our first 240 intubated patients with COVID-19. Of the 240, 195 were stratified into patients treated based on this protocol (ON-protocol, n = 91) and the control group, patients who received standard thromboprophylaxis (OFF-protocol, n = 104). All patients were admitted to the Stony Brook University Hospital intensive care units (ICUs) between February 7th, 2020 and May 17, 2020 and were otherwise treated in the same manner for all aspects of COVID-19 disease. Results: We found that the overall mortality was significantly lower ON-protocol compared to OFF-protocol (27.47 vs. 58.66%, P < 0.001). Average maximum D-dimer levels were significantly lower in the ON-protocol group (7,553 vs. 12,343 ng/mL), as was serum creatinine (2.2 vs. 2.8 mg/dL). Patients with poorly controlled D-dimer levels had higher rates of kidney dysfunction and mortality. Transfusion requirements and serious bleeding events were similar between groups. To address any possible between-group differences, we performed a propensity-matched analysis of 124 of the subjects (62 matched pairs, ON-protocol and OFF-protocol), which showed similar findings (31 vs. 57% overall mortality in the ON-protocol and OFF-protocol group, respectively). Conclusions: D-dimer-driven anticoagulation appears to be safe in patients with COVID-19 infection and is associated with improved survival. What This Paper Adds: It has been shown that hypercoagulability in patients with severe COVID-19 infection leads to thromboembolic complications and organ dysfunction. Anticoagulation has been variably administered to these patients, but it is unknown whether routine or escalated thromboprophylaxis provides a survival benefit. Our data shows that escalated D-dimer driven anticoagulation is associated with improved organ function and overall survival in intubated COVID-19 ICU patients at our institution. Importantly, we found that timely escalation of this anticoagulation is critical in preventing organ dysfunction and mortality in patients with severe COVID-19 infection.

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Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

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