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

Table 1 Baseline characteristics of included randomized controlled trials

Ref.	Year	Country	Total patients (n)	PPI group (n)	Non-PPI group (n)	PPI used	DAPT agents used	Duration of study
Wei et al[25]	2016	China	207	123	84	Pantoprazole 40 mg	Aspirin and clopidogrel	6 months
Vaduganathan et al[24]	2016	Spain and United States	2676	870	1806	Omeprazole 20 mg	Aspirin and clopidogrel	110 days
Jensen et al[23]	2017	Denmark	2009	997	1012	Pantoprazole 40 mg	Aspirin and clopidogrel or ticagrelor	1 year
Zhang et al[27]	2020	China	86	43	43	Omeprazole	Aspirin and ticagrelor	6 months
Ren et al[26]	2011	China	172	86	86	Omeprazole	Aspirin and clopidogrel	30 days
Gao et al[22]	2008	China	237	114	123	Omeprazole	Aspirin and clopidogrel or ticagrelor	14 days

PPI: Proton pump inhibitor; DAPT: Dual antiplatelet therapy.

Table 2 Baseline characteristics of included observational retrospective studies

Ref.	Year	Country	Total patients (n)	PPI group (n)	Non-PPI group (n)	PPI used	DAPT agents used	Duration of study
Kang et al[31]	2025	Korea	71120	35560	35560	Non-selective PPI	PCI and DAPT	1 year
Kim et al[32]	2024	Korea	2266	1133	1133	Non-selective PPI	Aspirin and clopidogrel	15 years
Yamamoto et al[34]	2024	Japan	24563	11202	13361	Non-selective PPI	Aspirin plus clopidogrel or ticagrelor	3 years
Rossini et al[33]	2011	Italy	1328	1158	170	Omeprazole/pantoprazole/Lansoprazole	Aspirin and clopidogrel	12 months
Yasu et al[35]	2010	Japan	302	103	199	Rabeprazole	Aspirin and clopidogrel	395 days
Aihara et al[29]	2012	Japan	1000	500	500	Non-selective PPI	Aspirin and clopidogrel	1 year
Chitose et al[28]	2012	Japan	1270	331	939	Non-selective PPI	Aspirin and clopidogrel or ticagrelor	18 months
Häuptle et al[30]	2012	Switzerland	718	87	631	Non-selective PPI	Aspirin and clopidogrel	12 months

PPI: Proton pump inhibitor; DAPT: Dual antiplatelet therapy; PCI: Percutaneous coronary intervention.

Table 3 Certainty of evidence assessment using grading of recommendations, assessment, development, and evaluation

Certainty assessment							Number of patients		Effect		Certainty	Importance
Number of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	GI bleed-RCTs only	Placebo	Relative (95%CI)	Absolute (95%CI)
GI bleed-RCTs only
6	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	30/2564 (1.2%)	100/4093 (2.4%)	RR 0.37 (0.20-0.68)	15 fewer per 1000 (from 20 fewer to 8 fewer)	High	Critical
GI bleed-RCTs and omeprazole only
4	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	17/1113 (1.5%)	53/2058 (2.6%)	RR 0.45 (0.21-0.96)	14 fewer per 1000 (from 20 fewer to 1 fewer)	High	Critical
GI bleed- RCTs and pantoprazole
2	Randomized trials	Not serious	Not serious	Not serious	Serious3	None	12/1120 (1.1%)	30/1096 (2.7%)	RR 0.28 (0.05-1.55)	20 fewer per 1000 (from 26 fewer to 15 more)	Moderate1,2	Critical
GI bleed-observational only
8	Non-randomized studies	Serious1	Not serious	Not serious	Serious2	All plausible residual confounding would suggest spurious effect, while no effect was observed	737/49743 (1.5%)	965/51554 (1.9%)	RR 0.00 (-0.01 to 0.00)	5 fewer per 1000 (from 10 fewer to 1 more)	Very low1,2	Important
Upper GI bleed-RCTs only
3	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	16/1981 (0.8%)	37/2941 (1.3%)	RR 0.50 (0.28-0.89)	6 fewer per 1000 (from 9 fewer to 1 fewer)	High	Critical
2	Randomized trials	Not serious	Not serious	Not serious	Not serious	None	8/984 (0.8%)	24/1929 (1.2%)	RR 0.42 (0.19-0.91)	7 fewer per 1000 (from 10 fewer to 1 fewer)	High	Critical
Upper GI bleed-observational studies only
2	Non-randomized studies	Serious1	Not serious	Not serious	Serious2	All plausible residual confounding would suggest spurious effect, while no effect was observed	17/190 (8.9%)	77/830 (9.3%)	RR 0.89 (0.16-5.02)	10 fewer per 1000 (from 78 fewer to 373 more)	Very low1,2	Critical
Lower GI bleed-observational studies only
3	Non-randomized studies	Serious1	Not serious	Not serious	Serious2	All plausible residual confounding would suggest spurious effect, while no effect was observed	170/11392 (1.5%)	146/14191 (1.0%)	RR 1.65 (1.31-2.06)	7 more per 1000 (from 3 more to 11 more)	Moderate1,2	Critical
Major bleed
2	Non-randomized studies	Serious1	Not serious	Not serious	Not serious	All plausible residual confounding would suggest spurious effect, while no effect was observed	141/35663 (0.4%)	240/35759 (0.7%)	RR 0.59 (0.48-0.73)	3 fewer per 1000 (from 3 fewer to 2 fewer)	Low1	Critical
All-cause mortality-observational studies only
3	Non-randomized studies	Serious1	Not serious	Not serious	Serious2	All plausible residual confounding would suggest spurious effect, while no effect was observed	70/2791 (2.5%)	43/1803 (2.4%)	RR 1.10 (0.75-1.63)	2 more per 1000 (from 6 fewer to 15 more)	Very low1,2	Important

¹Observational studies are prone to confounding, selection bias, and misclassification even if adjusted.

²95% confidence interval crosses the line of no effect (1.0), suggesting uncertainty.

³Wide confidence interval, almost crossing the line of non-effect.

CI: Confidence interval; RR: Relative risk; RCT: Randomized controlled trial; GI: Gastrointestinal.