Proton pump inhibitors for gastrointestinal bleeding prevention after percutaneous coronary intervention: Comparing evidence in dual antiplatelet therapy

Q: What are the key findings of this study?

Proton pump inhibitor co-therapy significantly reduced the risk of overall gastrointestinal bleeding (RR 0.39, 95% CI 0.21-0.74, P=0.004) in RCTs of patients on DAPT after PCI.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Acute coronary syndrome treated with dual antiplatelet therapy after percutaneous coronary intervention (n=106954). Intervention: Proton pump inhibitor (PPI) co-therapy (including omeprazole and pantoprazole) with dual antiplatelet therapy vs. Dual antiplatelet therapy without proton pump inhibitor. Primary outcome: Overall gastrointestinal bleeding (in RCTs) (RR 0.39, 95% CI 0.21-0.74, p=0.004).

Q: What does this research mean for the field?

Proton pump inhibitor co-therapy significantly reduces the risk of overall and upper gastrointestinal bleeding in patients receiving dual antiplatelet therapy following percutaneous coronary intervention. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

Rohab Sohail; Zaraq Khan; Haider Hussain Shah; Jason Orciuolo; Dwight Fan; Rohan D. Patel; Ana Estrada Zamudio; Shahryar Chaudhry; Ridda Khattak; Mithil Gowda Suresh

doi:10.3748/wjg.120932

October 20, 2026World Journal of GastroenterologyOpen Access

Proton pump inhibitors for gastrointestinal bleeding prevention after percutaneous coronary intervention: Comparing evidence in dual antiplatelet therapy

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Key result

PPI co-therapy cuts GI bleeding risk ~61% in post-PCI patients on DAPT.

RR 0.39
95% CI 0.21-0.74
P=0.004
n=106,954

Why the study?

Proton pump inhibitors are commonly co-prescribed to mitigate gastrointestinal bleeding risk from DAPT after PCI, but concerns about potential drug interactions, particularly with clopidogrel, have led to clinical uncertainty.

Does proton pump inhibitor co-therapy reduce gastrointestinal bleeding and all-cause mortality in adult patients with acute coronary syndrome receiving dual antiplatelet therapy after percutaneous coronary intervention?

Key Points

To evaluate the impact of proton pump inhibitor co-therapy on overall, major, upper, and lower gastrointestinal bleeding, as well as all-cause mortality, in patients receiving dual antiplatelet therapy following percutaneous coronary intervention.
Systematic literature search of PubMed, Cochrane Library, and Google Scholar through March 2025.
Included 14 studies (6 randomized controlled trials and 8 observational studies) comprising 106,954 adult patients (5,387 in trials and 101,567 in observational cohorts) on dual antiplatelet therapy with or without proton pump inhibitors.
Random-effects meta-analysis was performed to estimate pooled relative risks (RRs) and 95% confidence intervals (CIs).
In randomized controlled trials, proton pump inhibitor use significantly reduced the risk of overall gastrointestinal bleeding (RR = 0.39; 95% CI: 0.21–0.74; P = 0.004) and upper gastrointestinal bleeding (RR = 0.50; 95% CI: 0.28–0.89; P = 0.02), with benefit most prominent for omeprazole (RR = 0.45; 95% CI: 0.21–0.96; P = 0.04).
Observational studies showed a significant reduction in major bleeding events (RR = 0.59; 95% CI: 0.48–0.72; P < 0.00001) but an increased risk of lower gastrointestinal bleeding (RR = 1.65; 95% CI: 1.31–2.06; P < 0.0001).
Observational studies showed no significant effect on all-cause mortality (RR = 1.10; 95% CI: 0.75–1.63; P = 0.62), total gastrointestinal bleeding (RR = 0.00; 95% CI: -0.01 to 0.00; P = 0.27), or upper gastrointestinal bleeding (RR = 0.89; 95% CI: 0.16–5.02; P = 0.90).

Study Design

Type

Meta-Analysis (n=106,954)

Multicenter

Yes

Structured PICO

Does proton pump inhibitor co-therapy reduce gastrointestinal bleeding and all-cause mortality in adult patients with acute coronary syndrome receiving dual antiplatelet therapy after percutaneous coronary intervention?

P

Population

106,954 adult patients (5,387 in 6 RCTs and 101,567 in 8 observational studies) with acute coronary syndrome receiving dual antiplatelet therapy following percutaneous coronary intervention.

I

Intervention

Proton pump inhibitor (PPI) co-therapy (including omeprazole and pantoprazole) added to dual antiplatelet therapy (DAPT).

C

Comparator

Dual antiplatelet therapy (DAPT) without proton pump inhibitor (PPI) co-therapy (non-PPI users).

O

Outcome

Total gastrointestinal (GI) bleed eventssafety

Main Result

Relative Risk: 0.39 (95% CI 0.21–0.74)

p-value: p=0.004

This meta-analysis demonstrates that PPI co-therapy (particularly omeprazole) significantly reduces overall and upper GI bleeding in RCTs of post-PCI patients on DAPT without increasing mortality, while identifying a hypothesis-generating increase in lower GI bleeding in observational cohorts.

Limitations

Notable heterogeneity among included studies in design, sample size, population characteristics, follow-up duration, and outcome definitions
Lower GI bleeding, major bleeding, and all-cause mortality were reported exclusively in observational studies, which are susceptible to confounding by indication and selection bias
Inability to stratify PPIs by dosage or total duration of treatment
Limited number of included studies (<10 per group) precluded funnel plot analysis for publication bias and meta-regression
Geographic concentration of studies (most RCTs in China and most observational studies in South Korea) may limit generalizability to Western populations
Notable heterogeneity among included studies with respect to design, sample size, population characteristics, follow-up duration, and outcome definitions.
Several important outcomes, including lower GI bleed, major bleed, and all-cause mortality, were reported exclusively in observational studies, which are susceptible to confounding, selection bias, and inconsistent endpoint reporting.
Stratified analyses by specific PPI type, dosage, duration, or adherence were limited, affecting subgroup comparisons between omeprazole and pantoprazole.
Publication bias and incomplete adjustment for concomitant medications (such as anticoagulants and NSAIDs) may have influenced outcomes.
Limited number of eligible studies per outcome (less than 10) precluded meta-regression and funnel plot analysis, and geographic concentration in China and Korea limits generalizability to Western populations.

Implication

Supports PPI co-therapy to reduce GI bleeding in post-PCI DAPT; strengthens RCT evidence for guideline consideration.

Abstract

BACKGROUND Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 inhibitor, is the standard of care following percutaneous coronary intervention (PCI), but it significantly increases the risk of gastrointestinal (GI) bleed.Proton pump inhibitors (PPIs) are commonly co-prescribed to mitigate this risk, though concerns about potential drug interactions, particularly with clopidogrel, have led to clinical uncertainty.AIM To evaluate the impact of PPI co-therapy on GI bleed, major bleed, upper and lower GI bleed, and all-cause mortality in patients receiving DAPT after PCI.METHODS A systematic literature search of PubMed, Cochrane Library, and Google Scholar was conducted through March 2025.Eligible studies included randomized controlled trials (RCTs) and observational studies reporting outcomes in adult patients receiving DAPT with or without PPI use.Primary outcomes included GI bleed, major bleed, upper and lower GI bleed, and all-cause mortality.A random-effects model was used to estimate pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTSFourteen studies (6 RCTs and 8 observational studies) involving 106954 patients (101567 in observational studies; 5387 in RCTs) were included.RCTs found that PPI use was associated with a significantly reduced risk of overall GI bleed (RR = 0.39; 95%CI: 0.21-0.74;P = 0.004), with this effect being most prominent in omeprazole subgroup (RR = 0.45; 95%CI: 0.21-0.96;P = 0.04).Moreover, PPI use significantly lowered the risk of upper GI bleed in RCTs (RR = 0.50; 95%CI: 0.28-0.89;P = 0.02).In observational studies, the PPI group was associated with an increased risk of lower 4 / 37 GI bleed (RR = 1.65; 95%CI: 1.31-2.06;P < 0.0001) and a decreased major bleed events (RR = 0.59; 95%CI: 0.48-0.72;P < 0.00001), these effects were not studied in RCTs.Observational studies failed to show any significant effect on all-cause mortality, total GI bleed, or upper GI bleed.CONCLUSION PPI co-therapy significantly reduces risk of overall GI bleed in DAPT-treated patients post-PCI.However, a modest increase in hypothesis-generated lower GI bleed found only in observational studies underscores the need for further studies to explore this association.

Discussion

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Cite This Study

Sohail et al. (2026) conducted a meta-analysis in Acute coronary syndrome treated with dual antiplatelet therapy after percutaneous coronary intervention (n=106,954). Proton pump inhibitor (PPI) co-therapy (including omeprazole and pantoprazole) with dual antiplatelet therapy vs. Dual antiplatelet therapy without proton pump inhibitor was evaluated on Overall gastrointestinal bleeding (in RCTs) (RR 0.39, 95% CI 0.21-0.74, p=0.004). Proton pump inhibitor co-therapy significantly reduced the risk of overall gastrointestinal bleeding (RR 0.39, 95% CI 0.21-0.74, P=0.004) in RCTs of patients on DAPT after PCI.

synapsesocial.com/papers/6ae28e94cbadf70daf6c430a https://doi.org/10.3748/wjg.120932

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Proton pump inhibitors for gastrointestinal bleeding prevention after percutaneous coronary intervention: Comparing evidence in dual antiplatelet therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Proton pump inhibitors for gastrointestinal bleeding prevention after percutaneous coronary intervention: Comparing evidence in dual antiplatelet therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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