Dataset Information

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

ABSTRACT:

Objectives

The comparative effectiveness and safety of proton pump inhibitors (PPIs) versus histamine-2 receptor blockers for stress ulcer prophylaxis in the cardiac surgical intensive care unit population is uncertain. Although the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial reported a higher risk of mortality in the PPI arm with no difference in gastrointestinal bleeding, detailed information on surgical variables and clinically relevant surgical subgroups was not available.

Methods

The analysis included all Canadian cardiac surgery patients enrolled in the PEPTIC trial. Data were electronically linked using unique patient identifiers to a clinical information system. Outcomes of interest included in-hospital mortality, gastrointestinal bleeding, Clostridium difficile infections, ventilator-associated conditions and length of stay.

Results

We studied 823 (50.6%) randomized to PPIs and 805 (49.4%) to histamine-2-receptor blockers. In the intention-to-treat analysis, there were no differences in hospital mortality [PPI: 4.3% vs histamine-2 receptor blockers: 4.8%, adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.55-1.70], gastrointestinal bleeding (3.9% vs 4.8%, aOR 1.09, 95% CI 0.66-1.81), C. difficile infections (0.9% vs 0.1%, aOR 0.18, 95% CI 0.02-1.59), ventilator-associated conditions (1.6% vs 1.7%, aOR 0.92, 95% CI 0.85-1.00) or median length of stay (9.2 vs 9.8 days, adjusted risk ratio 1.06, 85% CI 0.99-1.13). No significant treatment differences were observed among subgroups of interest or per-protocol populations.

Conclusions

In a secondary analysis of cardiac surgery patients enrolled in the PEPTIC trial in Canada, no differences in effectiveness or safety were observed between use of PPIs and histamine-2 receptor blockers for stress ulcer prophylaxis.

Clinical trial registration number

anzctr.org.au identifier: ACTRN12616000481471.

SUBMITTER: van Diepen S

PROVIDER: S-EPMC9334785 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

van Diepen Sean S Coulson Tim T Wang Xiaoming X Opgenorth Dawn D Zuege Danny J DJ Harris Jo J Agyemang Malik M Niven Daniel J DJ Bellomo Rinaldo R Wright Stephen E SE Young Paul J PJ Bagshaw Sean M SM

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 20220701 2

<h4>Objectives</h4>The comparative effectiveness and safety of proton pump inhibitors (PPIs) versus histamine-2 receptor blockers for stress ulcer prophylaxis in the cardiac surgical intensive care unit population is uncertain. Although the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial reported a higher risk of mortality in the PPI arm with no difference in gastrointestinal bleeding, detailed information on sur ...[more]

PMID: 35213716

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Project description:ImportanceProton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown.ObjectiveTo compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis.Design, setting, and participantsCluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital.InterventionsTwo stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs).Main outcomes and measuresThe primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay.ResultsAmong 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). 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 2333 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). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group.Conclusions and relevanceAmong ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication.Trial registrationanzctr.org.au Identifier: ACTRN12616000481471.

Project description:Histamine-2 receptor antagonists are commonly administered for stress ulcer prophylaxis in critically ill adults and may be associated with delirium development. We aimed to determine differential associations of histamine-2 receptor antagonist or proton-pump inhibitor administration with delirium development in patients admitted to a medical ICU.DesignRetrospective observational study using a deidentified database sourced from the University of North Carolina Health Care system. Participants were identified as having delirium utilizing an International Classification of Diseases-based algorithm. Associations among histamine-2 receptor antagonist, proton-pump inhibitor, or no medication administration and delirium were identified using relative risk. Multiple logistic regression was used to control for potential confounders including mechanical ventilation and age.SettingAcademic tertiary care medical ICU in the United States.PatientsAdults admitted to the University of North Carolina medical ICU from January 2015 to December 2019, excluding those on concurrent histamine-2 receptor antagonists and proton-pump inhibitors in the same encounter.InterventionsNone.Measurements and main resultsWe identified 6,645 critically ill patients, of whom 29% (n = 1,899) received mechanical ventilation, 45% (n = 3,022) were 65 or older, and 22% (n = 1,487) died during their medical ICU encounter. Of the 6,645 patients, 31% (n = 2,057) received an histamine-2 receptor antagonist and no proton-pump inhibitors, 40% (n = 2,648) received a proton-pump inhibitor and no histamine-2 receptor antagonists, and 46% (n = 3,076) had delirium. The histamine-2 receptor antagonist group had a greater association with delirium than the proton-pump inhibitor group compared with controls receiving neither medication, after controlling for mechanical ventilation and age (risk ratio, 1.36; 1.25-1.47; p < 0.001) and (risk ratio, 1.15; 1.07-1.24; p < 0.001, respectively).ConclusionsHistamine-2 receptor antagonists are more strongly associated with increased delirium than proton-pump inhibitors. Prospective studies are necessary to further elucidate this association and to determine if replacement of histamine-2 receptor antagonists with proton-pump inhibitors in ICUs decreases the burden of delirium in critically ill patients.

Project description:Background and aimsPotassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to Proton-Pump Inhibitors (PPIs) in this setting remain controversial.MethodsThe efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs).ResultsSeven studies and 1,168 patients were included. The pooled eradication rate determined by Intention-To-Treat (ITT) analysis was 90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95% CI] = 1.17 [1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superiority of P-CABs (pooled eradication rate = 92.4% vs. 77.8%; pooled RR [95% CI] = 1.14 [1.03-1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate = 91.8% vs. 76.4%; pooled RR [95% CI] = 1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate = 93.0% vs. 78.6%; pooled RR [95% CI] = 1.13 [1.02-1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as determined in the ITT (75.0% vs. 66.0%, pooled RR [95% CI] = 1.11 [0.69-1.78], p = 0.66) and PP (85.7% vs. 70.0%, pooled RR [95% CI] = 1.20 [0.82-1.75], p = 0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate = 89.6% vs. 73.9%; RR [95% CI] = 1.21 [1.14-1.29], p < 0.01) and the PP analysis (pooled eradication rate = 92.0% vs. 75.7%; RR [95% CI] = 1.18 [1.06-1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate = 93.8% vs. 85.2%; RR [95% CI] = 1.10 [0.99-1.22], p = 0.07) or PP analysis (pooled eradication rate = 95.0% vs. 90.8%; RR [95% CI] = 1.05 [0.98-1.14], p = 0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABs vs. PPIs: 33.6% vs. 40.0%; RR [95% CI] = 0.84 [0.71‒1.00], p = 0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p = 0.44 and p = 0.67, respectively).ConclusionsThe efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was comparable, as was the incidence of adverse events.

Project description:BackgroundProton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.MethodsThis pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.ResultsIn total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.ConclusionsPPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.

Dataset Information

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

Objectives

Methods

Results

Conclusions

Clinical trial registration number

Publications

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

Similar Datasets

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