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PEPTIC RCT – PPI or H2-blocker for Ulcer Prophylaxis?

February 28, 2020

Written by Clay Smith

Spoon Feed
There was no difference in 90-day mortality when comparing proton pump inhibitors (PPI) to H2-receptor blockers (H2RB) for stress ulcer prophylaxis in critically ill patients.

Why does this matter?
Which is better for peptic ulcer prophylaxis in critically ill patients, H2RBs or PPIs?

Was mortality the best primary outcome here?
This was a massive cluster, crossover RCT in 50 ICUs, with almost 27,000 patients who received preferential PPI use for 6 months or preferential H2RB use for 6 months, and then each crossed over. There was no difference in the primary outcome, 90-day mortality*. But there was significant contamination of the groups, which may have muted any effect. As a secondary outcome, there was less clinically significant GI bleeding in the PPI group vs H2RB, 1.3% vs 1.8%; risk ratio 0.73 (95%CI 0.57 to 0.92); NNT = 200. There was no difference in C. difficile infection between groups. It appears to me there is a state of equipoise here. You can pick either agent. Based on this, I would favor a PPI, but many would disagree and say the opposite.

Another Spoonful
There has been a lot of talk about this article. St. Emlyn’s recommends preferential H2RB over PPI, given the slight, non-significant increase in mortality and increase in some subgroups. PulmCrit disagrees. I think you can pick either one, and I actually favor the PPI – but that is just me.

Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA. 2020 Jan 17. doi: 10.1001/jama.2019.22190. [Epub ahead of print]

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*”There were 26,771 patients (99.2%) included in the mortality analysis; 2459 of 13,415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2,333 of 13,356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95%CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95%CI, −0.01 to 1.88] percentage points; P = .054).”

What are your thoughts?