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higher.20,21 Nevertheless, a conclusion regarding the most
appropriate agent (ie, PPI or H2RA), solely based on the
SUP-ICU trial, cannot be made. Second pertains to the
cost-effectiveness of SUP. Cost-effectiveness accounts for
all related costs of a particular therapy including drug
acquisition costs, treatment benefits, and adverse effects.
Pharmacoeconomic analyses comparing PPI therapy with
H2RAs have demonstrated the incidence of pneumonia as
one of the primary drivers of incremental costs.33-35 The
fact that no difference in pneumonia rates was recognized in
the SUP-ICU trial could impact future pharmacoeconomic
analyses. Further studies are needed. Next, the SUP-ICU
trial was conducted in ICU patients who were at high risk for
stress-related mucosal bleeding. These data should not be
extrapolated to patients who are at low risk or those in a nonICU setting. The practice of providing routine SUP to these
patients should be discouraged. A pharmacist-led SUP management program has been shown to reduce inappropriate
use of acid suppressing agents.36 Finally, the most appropriate duration for SUP administration remains a clinical controversy. Future trials should evaluate the risk-benefit ratio
of SUP as it relates to duration of therapy.

Hospital Pharmacy 55(2)
organ support therapy (eg, mechanical ventilation, renal
replacement therapy), and have multiple coexisting disease
states, disorders of coagulation (eg, coagulopathy, liver disease), or severe neurologic injury (eg, severe traumatic brain
injury). Stress ulcer prophylaxis should be administered for as
long as patients remain severely ill. There may be some benefit with SUP even in patients who are receiving enteral feeds
particularly during the acute phase of critical illness. As critical illness subsides, it is anticipated that the risk of CIB may
also subside; thus, some patients may require only a few days
of therapy rather than a prolonged course. It may not be necessary to administer SUP for the entire duration of mechanical
ventilation or the complete ICU length of stay. This may lead
to a more favorable balance between bleeding avoidance and
infectious risk. Future randomized controlled trials are ongoing, and upcoming evidence-based guidelines will provide
further insight on the role of acid-suppressive therapy for SUP.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding

Future Trials
The SUP-ICU trial provides tremendous insight on the provision of SUP. Building on the success of this trial, other ongoing clinical trials will collectively redefine the landscape for
SUP. Re-evaluating the Inhibition of Stress Erosions
(REVISE) is a large multicenter randomized controlled trial
comparing pantoprazole with placebo in high-risk ICU
patients.37 The primary outcome measure is CIB. The PEPTIC
(Proton Pump Inhibitors versus Histamine-2 Receptor
Blockers for Ulcer Prophylaxis Therapy in the Intensive Care
Unit) study is a cluster randomized, crossover, registryembedded trial comparing PPIs with H2RAs in mechanically
ventilated patients.38 The primary endpoint will be in-hospital
mortality. Finally, SIREN (Sup-Icu RENal) is an observational study evaluating patients included in the SUP-ICU trial
that will address the benefits and harms of SUP specifically in
ICU patients in need of renal replacement therapy.39

Summary
The SUP-ICU trial is a landmark study describing the provision of SUP in a modern-day setting of ICU practice. It represents the first large-scale trial revisiting the overall value of
this widespread intervention. It is important for clinicians to
critically evaluate which patients should receive SUP recognizing the benefits and risks associated with acid suppressive
therapy. The decision to administer SUP must be individualized and only considered in patients who are at high risk for
stress ulcer-related CIB. Although risk cannot be determined
based on the presence or absence of a single factor, high-risk
patients generally consist of those patients who have a high
severity of illness (eg, shock, high organ-failure score), require

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs
Jeffrey F. Barletta
Mitchell S. Buckley

https://orcid.org/0000-0002-9054-8218
https://orcid.org/0000-0002-3385-8105

References
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Pharmacoepidemiology of stress ulcer prophylaxis in the
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8. Barletta JF, Bruno JJ, Buckley MS, Cook DJ. Stress ulcer prophylaxis. Crit Care Med. 2016;44:1395-1405.

https://www.orcid.org/0000-0002-9054-8218 https://www.orcid.org/0000-0002-3385-8105

Hospital Pharmacy - April 2020

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