Evaluation of low-dose aspirin use among COVID-19 critically ill patients: A Multicenter Propensity Score Matched Study

Abstract BackgroundMultiple medications with anti-inflammatory effects have been used to manage the hyper-inflammatory response associated with COVID-19. Aspirin is used widely as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. Its role in hospitalized COVID-19 patients has been assessed and evaluated in the literature. However, no data regards its role in COVID-19 critically ill patients. Therefore, this study aims to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in COVID-19 critically ill patients. MethodThis is a multicenter, retrospective cohort study for all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome is the in-hospital mortality; other outcomes were considered secondary. Propensity score-matched used based on patient’s age, SOFA score, MV status within 24 hours of ICU admission, prone position status, ischemic heart disease (IHD), and stroke as co-existing illness. We considered a P value of < 0.05 statistically significant.ResultsA total of 1033 patients were eligible; 352 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality (HR (95%CI): 0.73 (0.56, 0.97), p-value=0.03) were lower in patients who received aspirin during hospital stay. On the other hand, patients who received aspirin have a higher risk of major bleeding compared to the control group (OR (95%CI): 2.92 (0.91, 9.36), p-value=0.07); but was not statistically significant.ConclusionAspirin use in COVID-19 critically ill patients may have a mortality benefit; nevertheless, it may be linked with an increased risk of significant bleeding. The benefit-risk evaluation for aspirin usage during an ICU stay should be tailored to each patient.

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Evaluation of low-dose aspirin use among COVID-19 critically ill patients: A Multicenter Propensity Score Matched Study

10.21203/rs.3.rs-872891/v1 ◽

2021 ◽

Author(s):

Abdullah Al Harthi ◽

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

...

Keyword(s):

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

P Value ◽

Dose Aspirin ◽

Increased Risk ◽

Low Dose Aspirin ◽

Anti Inflammatory

Abstract BackgroundMultiple medications with anti-inflammatory effects have been used to manage the hyper-inflammatory response associated with COVID-19. Aspirin is used widely as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. Its role in hospitalized COVID-19 patients has been assessed and evaluated in the literature. However, no data regards its role in COVID-19 critically ill patients. Therefore, this study aims to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in COVID-19 critically ill patients. MethodThis is a multicenter, retrospective cohort study for all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay.The primary outcome is the in-hospital mortality; other outcomes were considered secondary. Propensity score-matched used based on patient’s age, SOFA score, MV status within 24 hours of ICU admission, prone position status, ischemic heart disease (IHD), and stroke as co-existing illness. We considered a P value of < 0.05 statistically significant.ResultsA total of 1033 patients were eligible; 352 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality (HR (95%CI): 0.73 (0.56, 0.97), p-value=0.03) were lower in patients who received aspirin during hospital stay. On the other hand, patients who received aspirin have a higher risk of major bleeding compared to the control group (OR (95%CI): 2.92 (0.91, 9.36), p-value=0.07); but was not statistically significant.ConclusionAspirin use in COVID-19 critically ill patients may have a mortality benefit; nevertheless, it may be linked with an increased risk of significant bleeding. The benefit-risk evaluation for aspirin usage during an ICU stay should be tailored to each patient.

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Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: a two center propensity-score matched study

Critical Care ◽

10.1186/s13054-021-03785-1 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Abdulrahman I. Al Shaya ◽

Abdullah Kharbosh ◽

Raed Kensara ◽

...

Keyword(s):

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Adjunctive Therapy ◽

Zinc Sulfate ◽

Statistical Significance ◽

Kidney Injury ◽

Additional Treatment ◽

Icu Stay

Abstract Background Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. Methods Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. Results A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37–1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19–1.06; p = 0.07); however, it did not reach statistical significance. Conclusion The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.

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Statins’ safety and impact on the clinical outcomes in COVID-19 critically ill patients: A Multicenter, Cohort Study

10.21203/rs.3.rs-828175/v2 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

The Impact ◽

Statin Use

Abstract Purpose The complications of Severe Corona Virus Disease 2019 (COVID-19) are attributed to the overproduction of early response proinflammatory cytokines, causing a systemic hyperinflammatory state. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic and anti-inflammatory effects, which are independent of their cholesterol-lowering activity. This study investigates the impact of statin use on the outcome of critically ill patients with COVID-19. Methods A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on statin use during ICU stay and were matched with a propensity score which was based on patient’s age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality. Other outcomes were considered secondary... Results A total of 1049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The 30-day (hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03) and in-hospital mortality (hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004) were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin have a lower risk of hospital-acquired pneumonia (OR 0.48(95% CI 0.32, 0.69), P = < 0.001), lower levels of markers of inflammation on follow up and no increased risk of liver injury. Conclusion The use of statin during ICU stay in COVID-19 critically ill patients may have a beneficial role and survival benefits with a good safety profile.

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Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study

Scientific Reports ◽

10.1038/s41598-021-96703-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Khalid Bin Saleh ◽

Hisham A. Badreldin ◽

Abdullah Al Harthi ◽

...

Keyword(s):

Ascorbic Acid ◽

Propensity Score ◽

Propensity Score Matching ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Incidence ◽

Adjunctive Therapy ◽

Low Dose ◽

P Value ◽

Severity Scores

AbstractAscorbic acid represents an appealing option for clinicians to utilize in the context of the global COVID-19 pandemic due to its proposed clinical efficacy, relative safety, and low cost. The aim of this study was to evaluate the efficacy and safety of using ascorbic acid in supplemental doses as adjunctive therapy for patients critically ill with COVID-19. This was a two-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 diagnosis between March 1st and December 31st, 2020, were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the clinical outcomes of low-dose ascorbic acid as adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systematic use of corticosteroids, and study centers. A number of 739 patients were included in this study, among whom 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality or the 30-day mortality [OR (95% CI) 0.77 (0.47, 1.23), p value = 0.27 and OR (95% CI) 0.73 (0.43, 1.20), p value = 0.21, respectively]. Using ascorbic acid was associated with a lower incidence of thrombosis compared with the non-ascorbic-acid group [6.1% vs. 13% respectively; OR (95% CI) 0.42 (0.184, 0.937), p value = 0.03]. Low dose of ascorbic acid as an adjunctive therapy in COVID-19 critically ill patients was not associated with mortality benefits, but it was associated with a lower incidence of thrombosis. Further studies are required to confirm these findings.

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Statins’ safety and impact on the clinical outcomes in COVID-19 critically ill patients: A Multicenter, Cohort Study

10.21203/rs.3.rs-828175/v1 ◽

2021 ◽

Author(s):

◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

The Impact ◽

Statin Use

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Statins’ safety and impact on the clinical outcomes in COVID-19 critically ill patients: A Multicenter, Cohort Study

10.21203/rs.3.rs-828175/v3 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Statin Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

Statin Use

Abstract Background The cardiovascular complications of Severe Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. Statins are known to have pleiotropic and anti-inflammatory effects and may influence viral transmission along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the association of statin use on the outcome of critically ill patients with COVID-19. MethodsA multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on statin use during ICU stay and were matched with a propensity score based on patient’s age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 days Ventilator-free days (VFDs) and ICU complications were secondary endpoints. ResultsA total of 1049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The 30-day (hazard ratio 0.75 (95% CI 0.58, 0.98), P=0.03) and in-hospital mortality (hazard ratio 0.69 (95% CI 0.54, 0.89), P=0.004) were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin had a lower risk of hospital-acquired pneumonia (OR 0.48(95% CI 0.32, 0.69), P=<0.001), lower levels of markers of inflammation on follow up and no increased risk of liver injury. ConclusionThe use of statin during ICU stay in COVID-19 critically ill patients may have a beneficial role and survival benefits with a good safety profile.

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High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10194465 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4465

Author(s):

José María Mora-Luján ◽

Manel Tuells ◽

Abelardo Montero ◽

Francesc Formiga ◽

Narcís A. Homs ◽

...

Keyword(s):

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

Invasive Mechanical Ventilation ◽

Hospital Length Of Stay ◽

High Dose ◽

Icu Admission ◽

High Dose Methylprednisolone

Corticosteroids are largely recommended in patients with severe COVID-19. However, evidence to support high-dose methylprednisolone (MP) pulses is not as robust as that demonstrated for low-dose dexamethasone (DXM) in the RECOVERY trial. This is a retrospective cohort study on severe, non-critically ill patients with COVID-19, comparing 3-day MP pulses ≥ 100 mg/day vs. DXM 6 mg/day for 10 days. The primary outcome was in-hospital mortality, and the secondary outcomes were need of intensive care unit (ICU) admission or invasive mechanical ventilation (IMV). Propensity-score matching (PSM) analysis was applied. From March 2020 to April 2021, a total of 2,284 patients were admitted to our hospital due to severe, non-critically ill COVID-19, and of these, 189 (8.3%) were treated with MP, and 493 (21.6%) with DXM. The results showed that patients receiving MP showed higher in-hospital mortality (31.2% vs. 17.8%, p < 0.001), need of ICU admission (29.1% vs. 20.5%, p = 0.017), need of IMV (25.9% vs. 13.8, p < 0.001), and median hospital length of stay (14 days vs. 11 days, p < 0.001). Our results suggest that treatment with low-dose DXM for 10 days is superior to 3 days of high-dose MP pulses in preventing in-hospital mortality and need for ICU admission or IMV in severe, non-critically ill patients with COVID-19.

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Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration

Cell & Bioscience ◽

10.1186/s13578-019-0369-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Yong Xie ◽

Meng Pan ◽

Yanpan Gao ◽

Licheng Zhang ◽

Wei Ge ◽

...

Keyword(s):

Bone Formation ◽

Bone Remodeling ◽

Low Dose ◽

High Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Dose Dependent ◽

High Dose Aspirin

AbstractThe failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150–300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.

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