Published in:
01-04-2016 | Editorial
Association of prior antiplatelet agents with mortality in sepsis patients
Published in: Intensive Care Medicine | Issue 4/2016
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Platelet activation is not only an essential component of primary hemostasis but also plays a critical role in disease progression during sepsis. Sepsis involves inflammatory processes through releasing of several inflammatory mediators, such as interleukin (IL)-1β, IL-8, monocyte chemotactic protein 1, and tumor necrosis factor alpha [1], and then influences microvascular thrombosis formation and both innate and adaptive immunity [2]. Thus, attenuation of platelet activation is suggested to be one possible treatment option for sepsis in preclinical studies [1]. Some retrospective observational studies have also revealed that prehospital antiplatelet use was associated with decreased mortality rate in sepsis patients [3‐6], but there is still a place for argument until studies provide strong evidence to support whether antiplatelet drugs are a possible adjuvant treatment choice in sepsis (Table 1).
Table 1
Brief summary of recent cohort studies on the association between antiplatelet therapy and sepsis
|
Literature
|
Study design
|
Agent
|
Date
|
Patient
|
Investigation
|
Outcome
|
Limitation
|
|---|---|---|---|---|---|---|---|
|
Eisen et al. [4]
|
Retrospective cohort
|
ASA
|
2000–2009
|
5523 patients with SIRS; 2082 on ASA; propensity score matched 1445 pairs of ASA users and non-users
|
Association of ASA administration at the time of SIRS/sepsis and mortality
|
Reduced mortality in ASA group
|
Treatment bias of ASA at the time of enrollment
|
|
O’Neal et al. [8]
|
Cross-sectional analysis of prospective cohort
|
ASA, statins
|
2006–2008
|
575 medical or surgical ICU patients
|
Association of prehospital statin, APT, or combination with risk of sepsis, ARDS, and mortality
|
Reduced risk of ARDS and severe sepsis for prehospital statin user, but not ASA user. No significant benefit on mortality rate
|
Uncontrolled administration of statins and aspirin
|
|
Valerio-Rojas et al. [8]
|
Retrospective cohort
|
ASA, clopidogrel
|
2007–2009
|
651 ICU patients with sepsis; 272 on APT; propensity matched 180 pairs of users and non-users
|
Association of APT before development of severe sepsis and outcome
|
No association between prehospital ASA use and mortality. Reduce incidence of ARDS/ALI and the need of mechanical ventilation
|
Inadequate patient number and power
|
|
Winning et al. [13]
|
Retrospective cohort
|
ASA, clopidogrel
|
2010
|
615 ICU patients; 179 received prehospital APT
|
Association of prehospital APT and mortality in critically ill patients
|
Reduction in mortality in APT group
|
Including non-sepsis critical patient
|
|
Losche et al. [14]
|
Retrospective
cohort
|
ASA
|
2011
|
834 ICU patients presenting severe sepsis or septic shock. 187 receiving ASA
|
Effect of ASA use during ICU stay on outcomes of severe sepsis patients
|
Reduce ICU mortality in ASA group
|
Unequal distribution of each cohort
|
|
Chen et al. [15]
|
Secondary analysis of prospective cohort
|
ASA
|
2006–2012
|
1149 ICU patients; 725 patients with sepsis; 287 on prehospital ASA treatment
|
Effect of prehospital ASA use on the risk of ARDS and outcomes in critical patients including sepsis subgroup
|
Reduce the risk of ARDS. No significant association with mortality
|
Inaccurate ASA prescription; underpowered
|
|
Otto et al. [6]
|
Retrospective cohort
|
ASA, clopidogrel
|
2013
|
886 ICU patients with sepsis
|
Association of APT during ICU stay on outcome of patients with sepsis
|
Reduction in mortality in ASA and clopidogrel groups, but not in ASA + clopidogrel group
|
Surgical ICU patients
|
|
Tsai et al. [3]
|
Observational cohort
|
ASA, clopidogrel, ticlopidine
|
2000–2010
|
683,421 patients with sepsis; 117,447 prehospital APT users; propensity score matched 186,374 pairs of users and non-users
|
Association of prehospital APT and mortality of sepsis
|
Reduction in mortality in prehospital APT user. Survival benefit was inversely proportional to the interval between drug discontinuation and sepsis onset
|
Claims database
|