Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis

Jiang, Luojia; Li, Yupei; Du, Hao; Zheng, Qin; Su, Baihai

doi:10.3389/fmed.2021.698935

Cited by 11 publications

(8 citation statements)

References 42 publications

(83 reference statements)

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“…Antithrombotics in context. Our findings are consistent with a subset of twelve previous meta-analyses (Abrahams 2022a 2 , Table 8) investigating the clinical utility of antithrombotics 10,16,17,18,19,20,21,22,23,24,25,26 and are discordant with a second subset of nine previous meta-analyses 27, 28, 29, 30, 31, 32, 33, 34, 35. The reason for the observed discrepancies in overall conclusion are unknown, however may be due to differences in eligibility criteria for included studies, alternative choice of sources for literature search or timing of the evidence synthesis.…”

Section: Discussionsupporting

confidence: 90%

Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis

Abrahams¹

2022

Preprint

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Aims: Covid-19 hematology is hallmarked by porphyrin dysmetabolism, altered hemostasis and erythropoietic distress. We hypothesize that antiporphyrics, antithrombotics and erythropoiesis stimulating agents (ESAs) may prove beneficial in the treatment of severe Covid-19. The objective of the current study was to systematically review and meta-analyse the mortality risk profile of hospitalized Covid-19 patients, when treated with each of the three interventions of interest - versus placebo, standard of care or non-intervention.Methods: Eligible studies were identified from: biorxiv and medrxiv, clinical trials govR4, covid19 trials tracker netR5, DISCOVERR2 (Ebsco), ICTRPR7, PubMedR1 and Google ScholarR3 during search period 27 May-07 June 2022. Risk of bias was assessed with SIGN, NIH and JBI checklists and results quantitatively synthesised for antiporphyrics plus antithrombotics studies. Quantitative synthesis was performed in RevMan 5.4R9 with random effects model meta-analysis. Publication bias was assessed in R by funnel plot, Egger’s regression and trimfill analysis (metafor).Results: Number and type of studies included was 6 RCTs for antiporphyrics, 16 cohort for antithrombotics, and 3 case report/series for ESAs. Both unadjusted and adjusted analyses suggested that hydroxychloroquine treatment was not significantly associated with mortality risk in hospitalised Covid-19 patients (RR 0.95 [0.71, 1.29], P=0.76; aHR 0.78 [0.51, 1.22], P=0.28). Interestingly, the direction of effect shifted further towards favoring intervention when only high quality studies were included in the analysis (unadjusted RR 0.80 [0.42, 1.55]) compared with low quality studies (unadjusted RR 1.59 [0.71, 3.53]) although neither were statistically significant (P=0.51 and P=0.26, respectively). Exposure to antithrombotics was associated with reduced in-hospital mortality risk in adjusted analysis (aOR 0.54 [0.33, 0.86], P=0.01; aHR 0.65 [0.52, 0.82], P=0.0003). Subgroup analysis of adjusted estimates showed that exposure to aspirin (aHR 0.62 [0.50, 0.77], P<0.00001) and heparin (aOR 0.35 [0.14, 0.90], P=0.03) individually were associated with reduced mortality risk. The finding was robust to type of regimen, with pre-admission exposure to antithrombotics (aHR 0.79 [0.67, 0.93], P=0.005) and aspirin (aHR 0.66 [0.52, 0.84], P=0.0009] both showing reduced mortality risk. Additionally, prophylactic dose antithrombotics were associated with reduced mortality (aHR 0.44 [0.32, 0.60], P<0.00001). Publication bias was negative by Egger’s regression test (P=0.95). The direction of effect remained significantly in favor of intervention after trim-and-fill analysis (P=0.0034). Discussion: We make an interim recommendation in favor of antithrombotics, with very low certainty of evidence. We make an interim recommendation in favor of either intervention or non-intervention for both antiporphyrics and ESAs, with low and very low certainty of evidence.

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Section: Discussionsupporting

confidence: 90%

Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis

Abrahams¹

2022

Preprint

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“…A meta-analysis of 4421 potentially relevant studies (of which only 2107 were identified as relevant) including 11 studies on the impact of anticoagulant treatment on COVID-19 mortality and bleeding events, indicates a reduction in the risk of mortality through anticoagulant therapy, even in critically ill patients admitted to intensive care. 63 The results of another prospective cohort study conducted on 6195 patients in 14 hospitals and 60 clinics in the United States show that SARS-CoV-2 is associated with a state of hypercoagulability and that the presence of cardiovascular, immunological and coagulatory comorbidities has been associated with a higher risk of death, especially for inpatients, ICUs and mechanically ventilated and non-ventilated patients. 64–66 …”

Section: Discussionmentioning

confidence: 99%

Analysis of Deaths and Favorable Developments of Patients with SARS-CoV-2 Hospitalized in the Largest Hospital for Infectious Diseases and Pneumo-Phthisiology in the West of the Country

Laza¹,

Dragomir²,

Musta³

et al. 2022

IJGM

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Purpose Romania is one of the European countries that has been hit the hardest by the severe acute respiratory syndrome caused by the new coronavirus SARS-CoV-2, with over 1.91 million reported cases and over 59,257 deaths. The aim of this study was to identify the main predictors of death in hospitalized patients. Patients and Methods In the period from 1 March 2020 to 30 June 2021, an observational, retrospective, randomized, case-control study was conducted, which included a sample of 139 patients who died in hospital and another sample of 275 patients who had been discharged in an improved or healed condition. Confirmation of COVID-19 cases was performed by RT-PCR from nasopharyngeal and oropharyngeal exudates. Statistical data were analyzed by logistic regression, Cox regression and a comparison of survival curves by the log-rank (Mantel-Cox) test. Results The most powerful logistic regression model identified the following independent predictors of death: history of coagulopathy HR = 30.73 [1.94–487.09], p = 0.015; high percentage of neutrophils HR = 1.09 [1.01–1.19], p = 0.027; and decreased blood-oxygenation HR = 53881.97 [1762.24–1647489.44], p < 0.001. Cox regression identified the following factors that influenced the evolution of cases: history of coagulopathy HR = 2.44 [1.38–4.35], p = 0.000; O 2 saturation HR = 0.98 [0.96–0.99], p = 0.043; serum creatinine HR = 1.23 [1.08–1.39], p = 0.001; dyspnea on admission HR = 2.99 [1.42–6.30], p = 0.004; hospitalization directly in the ICU HR = 3.803 [1.97–7.33], p < 0.001; heart damage HR = 16.76 [1.49–188.56], p = 0.022; and decreased blood-oxygenation HR = 35.12 [5.92–208.19], p < 0.001. Conclusion Knowledge of the predictors of death in hospitalized patients allows for the future optimization of triage and therapeutic case management for COVID-19.

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“…Early observational studies and a meta-analysis reported no difference in mortality in patients with COVID-19 who received AC therapy relative, but these studies suffered from small sample sizes, heterogenous patient populations, and unclear inclusion and exclusion criteria (14,35,36). In a recent meta-analysis of 11 studies investigating the impact of AC on mortality in a cohort of 20,748 hospitalized COVID-19 patients, AC therapy was found to be associated with a lower rate of in-hospital mortality in patients with COVID-19 (RR = 0.70, 95% CI 0.52 -0.93, p = 0.01) (37). A large observational study including 4,389 patients from New York, demonstrated that therapeutic AC was associated with a 47% reduction in the risk of in-hospital mortality (aHR= 0.53; 95% CI: 0.45 -0.62; p < 0.001) and 31% reduction in the intubation rate (aHR= 0.69; 95% CI: 0.51 -0.94; p = 0.02) compared with no AC (38).…”

Section: Discussionmentioning

confidence: 99%

Chronic Anti-Coagulation Therapy Reduced Mortality In Patients With High Cardiovascular Risk Early In COVID-19 Pandemic

Zaghloul¹,

Jammeh²,

Gibson

et al. 2022

Preprint

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Background: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviate these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients during the early phase of the pandemic in the United States. Methods: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous therapeutic AC for a least 30 days prior to or after their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). Results: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. Conclusion: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

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Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis

Cited by 11 publications

References 42 publications

Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis

Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis

Analysis of Deaths and Favorable Developments of Patients with SARS-CoV-2 Hospitalized in the Largest Hospital for Infectious Diseases and Pneumo-Phthisiology in the West of the Country

Chronic Anti-Coagulation Therapy Reduced Mortality In Patients With High Cardiovascular Risk Early In COVID-19 Pandemic

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