Table 1.

Description of included studies

Author(s)	Title	Year of publication	Type of study	Number of patients	Inclusion criteria	Primary outcome	Type of antiplatelet drug used	Severity scoring	Timing of APT	Duration of maximum follow-up	Definition of ALI/ARDS	Definition of sepsis
Winning et al.[35]	Antiplatelet drugs and outcome in severe infection: Clinical impact and underlying mechanisms	2009	Observational	224	Patients who were admitted to the hospital for CAP	Need for treatment in ICU Length of hospital stay	Aspirin, clopidogrel	SOFA 2.95±2.03 (control) versus 2.74±1.18 (APT)	Patients on APT for at least 6 months before admission	28 days
Winning et al.[34]	Antiplatelet drugs and outcome in mixed admissions to an ICU	2010	Observational	615	Patients admitted to the ICU within 24 h after arrival to the hospital	Death during ICU treatment or discharge from ICU	Aspirin, clopidogrel	APACHE II: 19 (13-19) (control) versus 25 (19-32) (APT)	Patients on APT before admission	Duration of ICU stay
Erlich et al.[25]	Prehospitalization APT is associated with a reduced incidence of ALI	2011	Observational	161	Age>18 years+at least one risk factor for ALI (high-risk trauma, aspiration, sepsis, shock, pneumonia, and pancreatitis)	Development of ALI or ARDS during hospitalization	Aspirin, clopidogrel, ticlopidine, cilostazol, dipyridamole, anagrelide, persantine	APACHE III: 39 (27-54) (control) versus 46 (34-57) (APT)	Patients on APT before admission		American- European Consensus Conference criteria[40]
Lösche et al.[50]	Do aspirin and other antiplatelet drugs reduce the mortality in critically ill patients?	2012	Observational	224	Patients admitted to the hospital with CAP	Length of hospital stay Admission to ICU	Aspirin, ticlopidine, clopidogrel	SOFA odds ratio 0.19 (0.04-0.87)	Patients on APT for at least 6 months before admission	Duration of hospital stay
Lösche et al.[50]	Do Aspirin and other antiplatelet drugs reduce the mortality in critically ill patients?	2012	Observational	834	ICU admission for severe sepsis or septic shock	ICU mortality	Aspirin	APACHE II: 22.6±9.2 (control) versus 24.1±8.3 (APT)		Duration of ICU stay
Eisen et al.[24]	Acetylsalicylic acid usage and mortality in critically ill patients with the SIRS and sepsis	2012	Observational	2890	Patients admitted to the ICU with SIRS	Hospital mortality	Aspirin	APACHE II: 17.78 (control) versus 17.47 (APT)	Patients on APT in the 24 h period at time of detection of SIRS			America College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria[48]
Losche et al.[29]	Association of prehospitalization aspirin therapy and ALI: results of a multicenter international observational study of at-risk patients	2012	Observational	3855	Admission to the hospital with the presence of at least one major risk factor for ALI and age>18 years.(aspiration, pneumonia, sepsis, shock, pancreatitis, high-risk trauma, or high-risk surgery)	Development of ALI/ARDS during hospitalization	Aspirin	APACHE II: 9 (5-14) (control) versus 12 (8-16) (APT)	Documentation of use or administration of APT at time of hospital admission	Duration of hospital stay	American- European Consensus Conference criteria[40]
Gross et al.[27]	Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of APT in pneumonia and critical illness	2013	Observational	23,882	Patients who received at least 6 consecutive prescriptions of clopidogrel	Incidence and severity of pneumonia	clopidogrel	NA	≥6 prescription claims of APT	Duration of hospital stay
Harr et al.[28]	APT is associated with decreased transfusion- associated risk of lung dysfunction, multiple organ failure, and mortality in trauma patients	2013	Observational	839	Blunt trauma mechanism, ED arrival within 6 h of injury, ED base deficit>6 mEq/L or ED systolic blood pressure<90 mm Hg, and a blood product transfusion within the first 12 h of ED arrival	Lung dysfunction defined by Denver lung dysfunction score of 2 or 3 Denver MOF score (>3) Mortality	Aspirin, ticlopidine, clopidogrel	NA	Patients on APT before trauma	28 days	Denver lung dysfunction score Grades 2 or 3, which corresponds to PaO2:FiO2 ratio<200
Valerio-Rojas et al.[33]	Outcomes of severe sepsis and septic shock patients on chronic antiplatelet treatment: A historical cohort study	2013	Observational	651	≥18 years, diagnosis of severe sepsis or septic shock at the time of ICU admission and use of APT before admission	Hospital mortality	Aspirin, clopidogrel, ticlopidine, dipyridamole	APACHE III: 55 (42-68) (control) versus 57.5 (46-74.8) (APT)	Patients on APT at time of ICU admission	Duration of hospital stay	American- European Consensus Conference criteria[40]	America College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria[48]
Otto et al.[31]	Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock	2013	Observational	886	Only patients with severe sepsis/septic shock and minimum ICU stay of 48 h	ICU mortality Discharge from ICU Hospital mortality	Aspirin, clopidogrel	NA	Patient on APT for at least 2 days during ICU stay	Duration of hospital stay
Faverio et al.[26]	Antiplatelets improve survival among critically ill mechanically ventilated patients	2014	Observational	150	Critically ill mechanically ventilated patients for 1 day or more managed at a tertiary medical ICU	Mortality during ICU and hospital stay	Aspirin, clopidogrel	APACHE II>25	Patient on prehospital or in-hospital APT	Duration of hospital stay
Chen et al.[23]	Prehospital aspirin use is associated with reduced risk of ARDS in critically ill patients: A propensity- adjusted analysis	2015	Observational	1149	Patient who are 18 years old or older admitted to the medical, surgical, cardiovascular, and trauma ICUs who remained in the ICU for at least 2 days	ARDS in first 4 days of ICU stay	Aspirin	NA	Patients on APT before admission	Duration of hospital stay	American- European Consensus Conference criteria[40]	America College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria[48]
Tsai et al.[32]	Association of prior antiplatelet agents with mortality in sepsis patients: A nationwide population-based cohort study	2015	Observational	683,421	All patients with a first time discharge diagnosis of sepsis	In-hospital mortality from sepsis	Aspirin, clopidogrel, ticlopidine	NA	Patients on APT currently or within 30 days before admission			ICD 9 code for sepsis
Mazzeffi et al.[30]	Preoperative aspirin use and lung injury after aortic valve replacement surgery: A retrospective cohort study	2015	Observational	375	All adult patients having aortic valve replacement surgery with cardiopulmonary bypass	Occurrence of ARDS	Aspirin	NA	Patients receiving preoperative APT		Berlin definition[67]
Boyle et al.[22]	Aspirin therapy in patients with ARDS is associated with reduced ICU mortality: A prospective analysis	2015	Observational	202	All adult patients (>16 years-old) requiring invasive mechanical ventilation	ICU mortality	Aspirin	APACHE II: 18 (13-24) in (control) versus 21 (17-24) (APT)	Patients on prehospital APT, in ICU APT or both	Duration of hospital stay	American- European Consensus Conference criteria[40]
Al Harbi et al.[48]	Association between aspirin therapy and the outcome in critically ill patients: A nested cohort study	2016	Observational	763	≥18-year-old with expected ICU length of stay of >48 h. Patients who were pregnant, had do-not-resuscitate status within 24 h of admission, were terminally ill or admitted to the ICU after cardiac arrest, seizures, liver transplantation, or burn injury were excluded	All cause ICU mortality and in-hospital mortality	Aspirin	APACHE II: 22.9±8.2 (control) versus 26.5±7.2 (APT)	Patients who had either continuation of a pre-ICU prescription or a newly prescribed APT in the ICU	Duration of ICU stay

CAP: Community-acquired pneumonia, SIRS: Systemic inflammatory response syndrome, APACHE: Acute Physiology and Chronic Health Evaluation, SOFA: Sequential Organ Failure Assessment, APT: Antiplatelet therapy, NA: Not available, ICU: Intensive Care Unit, ALI: Acute lung injury, ARDS: Acute respiratory distress syndrome, ED: Emergency department