Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching*

Trauer, James M.; Muhi, Stephen; McBryde, Emma S.; Harbi, Shmeylan Al; Arabi, Yaseen M.; Boyle, Andrew; Cartin‐Ceba, Rodrigo; Chen, Wei; Chen, Yung Tai; Falcone, Marco; Gajić, Ognjen; Godsell, Jack; Gong, Michelle N.; Kor, Daryl J.; Lösche, Wolfgang; McAuley, Daniel F.; O’Neal, Hollis R.; Osthoff, Michael; Otto, Gordon P.; Soßdorf, Maik; Tsai, Min Juei; Valerio-Rojas, Juan Carlos; Poll, Tom van der; Violi, Francesco; Ware, Lorraine B.; Widmer, Andreas F.; Wiewel, Maryse A.; Winning, Johannes; Eisen, Damon P.

doi:10.1097/ccm.0000000000002654

Cited by 38 publications

(21 citation statements)

References 44 publications

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“…A number of clinical studies in patients affected by diseases of different degrees of clinical severity (e.g., critically ill, admitted to ICUs, with sepsis, severe sepsis, community-acquired pneumonia) showed that the use of ASA was associated with lower mortality [ 116 , 117 ]. These beneficial effects of ASA have been confirmed by an individual patient data meta-analysis of published observational cohort data showing a reduced sepsis-related mortality in patients taking ASA prior to the onset of sepsis [ 118 ]. A more recent meta-analysis of ten cohort studies enrolling 689,897 patients with sepsis revealed that ASA, administered either before or after sepsis, reduced ICU or hospital mortality [ 119 ].…”

Section: Clinical Applications Of Acetylsalicylic Acid In Infectious mentioning

confidence: 84%

Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?

Bianconi

Violi

Fallarino

et al. 2020

Drugs

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115

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Severe Acute Respiratory Syndrome–Coronavirus-2 is responsible for the current pandemic that has led to more than 10 million confirmed cases of Coronavirus Disease-19 (COVID-19) and over 500,000 deaths worldwide (4 July 2020). Virus-mediated injury to multiple organs, mainly the respiratory tract, activation of immune response with the release of pro-inflammatory cytokines, and overactivation of the coagulation cascade and platelet aggregation leading to micro- and macrovascular thrombosis are the main pathological features of COVID-19. Empirical multidrug therapeutic approaches to treat COVID-19 are currently used with extremely uncertain outcomes, and many others are being tested in clinical trials. Acetylsalicylic acid (ASA) has both anti-inflammatory and antithrombotic effects. In addition, a significant ASA-mediated antiviral activity against DNA and RNA viruses, including different human coronaviruses, has been documented. The use of ASA in patients with different types of infections has been associated with reduced thrombo-inflammation and lower rates of clinical complications and in-hospital mortality. However, safety issues related both to the risk of bleeding and to that of developing rare but serious liver and brain damage mostly among children (i.e., Reye’s syndrome) should be considered. Hence, whether ASA might be a safe and reasonable therapeutic candidate to be tested in clinical trials involving adults with COVID-19 deserves further attention. In this review we provide a critical appraisal of current evidence on the anti-inflammatory, antithrombotic, and antiviral effects of ASA, from both a pre-clinical and a clinical perspective. In addition, the potential benefits and risks of use of ASA have been put in the context of the adult-restricted COVID-19 population.

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Section: Clinical Applications Of Acetylsalicylic Acid In Infectious mentioning

confidence: 84%

Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?

Bianconi

Violi

Fallarino

et al. 2020

Drugs

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115

134

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“…However, the study only included antiplatelet use in the 30 days prior to admission, and did not differentiate aspirin from other antiplatelet agents. Similarly, in a meta-analysis, Trauer, et al observed 7% lower sepsis mortality among pre-existing aspirin users, but most of the included studies did not differentiate between the use of aspirin and other antiplatelet agents [ 34 ]. Of note, in our series we observed a sepsis hospital mortality rate of only 9.2%, while the studies in the Trauer, et al study reported sepsis mortality ranging from 14 to 42%.…”

Section: Discussionmentioning

confidence: 99%

Aspirin use and long-term rates of sepsis: A population-based cohort study

et al. 2018

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ObjectiveSepsis is the syndrome of life-threatening organ dysfunction resulting from dysregulated host response to infection. Aspirin, an anti-inflammatory agent, may play a role in attenuating the inflammatory response during infection. We evaluated the association between aspirin use and long-term rates of sepsis as well as sepsis outcomes.MethodsWe analyzed data from 30,239 adults ≥45 years old in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was aspirin use, identified via patient interview. The primary outcome was sepsis hospitalization, defined as admission for infection with two or more systemic inflammatory response syndrome criteria. We fit Cox proportional hazards models assessing the association between aspirin use and rates of sepsis, adjusted for participant demographics, health behaviors, chronic medical conditions, medication adherence, and biomarkers. We used a propensity-matched analysis and a series of sensitivity analyses to assess the robustness of our results. We also examined risk of organ dysfunction and hospital mortality during hospitalization for sepsis.ResultsAmong 29,690 REGARDS participants with follow-up data available, 43% reported aspirin use (n = 12,869). Aspirin users had higher sepsis rates (hazard ratio 1.35; 95% CI: 1.22–1.49) but this association was attenuated following adjustment for potential confounders (adjusted HR 0.99; 95% CI: 0.88–1.12). We obtained similar results in propensity-matched and sensitivity analyses. Among sepsis hospitalizations, aspirin use was not associated with organ dysfunction or hospital death.ConclusionsIn the REGARDS cohort, baseline aspirin use was not associated with long-term rates of sepsis.

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“…Chen and coworkers found that critically ill patients taking aspirin had a significantly lower prevalence of adult respiratory distress syndrome (ARDS) (27% versus 34%; P ϭ 0.034) (21). Chronic aspirin therapy has been also associated with improved survival rates for both patients with CAP (13) and those with sepsis (22).…”

Section: Discussionmentioning

confidence: 99%

A Hypothesis-Generating Study of the Combination of Aspirin plus Macrolides in Patients with Severe Community-Acquired Pneumonia

Falcone

Russo

Shindo

et al. 2019

Antimicrob Agents Chemother

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While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of conventional antibiotic therapy. An observational study was conducted with patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, the United States, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to Infectious Diseases Society of America/American Thoracic Society criteria. Patients were divided into 4 groups, i.e., (i) the aspirin-only group (ASG), (ii) the macrolide-only group (MG), (iii) the aspirin plus macrolide group (ASMG), or (iv) the neither aspirin nor macrolide group (NASMG). Survival rates for the 4 groups were evaluated after adjustment for confounders and after weighting by propensity score. A total of 1,295 patients were included in the analysis. There were 237 patients (18.3%) in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. The mortality rate at 30 days was 15.5% in the ASMG, compared to 28.2% in the NASMG, 23.8% in the MG, and 21.1% in the ASG. After propensity score analysis, receipt of aspirin plus macrolide (hazard ratio, 0.71 [95% confidence interval, 0.58 to 0.88]; P = 0.002) was associated with a higher 30-day survival rate. This is a hypothesis-generating study in which data suggest that the combination of aspirin plus a macrolide improves 30-day survival rates for patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.

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Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching*

Cited by 38 publications

References 44 publications

Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?

Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?

Aspirin use and long-term rates of sepsis: A population-based cohort study

A Hypothesis-Generating Study of the Combination of Aspirin plus Macrolides in Patients with Severe Community-Acquired Pneumonia

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