Title: Widespread use of proton pump inhibitors or potassium-competitive acid blocker has
changed the status of gastrointestinal bleeding in patients with ischemic heart disease: Real-
world data from high volume centers
Version: 2 Date: 28 Oct 2023
Reviewer's report:
A good study but with a relatively short follow up and being retrospective bears the limitations
of missing out important data.
The following points needs clarification from the authors
[1] Please define severity grading of anemia, chronic kidney disease, cerebrovascular disease
[mild moderate severe etc]. Was it done by level of hemoglodin, GFR and type of CVA?
[2] It appears that patients of GI bleed included in study were severe ones [“that required
endoscopic hemostasis, hospitalization or blood transfusion, or fatal gastrointestinal bleeding”]
Were mild GI bleed that stopped by itself excluded? That would underestimate the risk or
incidence of GI bleed. This may be the reason why incidence of GI bleed is so small.
[3] Table 1. All odds ration are not mentioned. Please calculate them for all parameters. Compare
the haemoglobin and Prothrombin times of both groups in table. [It is likely that P.times must
have been done in most patients as they were on anticoagulants/antiplatelet agents.]. Hemoglobin
may be a surrogate for bleeding. Also mention the comorbidities and use of other medications
like steroids/NSAIDs and compare them in the two groups.
[4] Table 2. It should be mentioned whether any combination of PPI and PCAB were being
used. Similarly how many were using combinations of DAPT, DOAC, warfarin etc. All odds
ratio should be mentioned.
[5] It is only mentioned about endoscopic hemostasis in the paper. Did all bleeding patients
undergo endoscopy?  How was small intestinal pathology diagnosed?
[6] In the discussion section it is mentioned “Although we found some statistically significant
factors associated with gastrointestinal bleeding, they might be the result of type II errors due to
the very small number of gastrointestinal bleeding cases. Therefore, multicenter or prospective
studies are necessary to obtain more accurate data.” In this context the long term prospective
study “Incidence and outcome of gastrointestinal bleeding in patients receiving aspirin with or
without clopidogrel over 10 years - An observational study. December 2022, Journal of Family
Medicine and Primary care.” can be quoted which is a study with follow up of 10 years and
derives many of the factors associated with GI bleed on long term. The study is also relevant
for the sites of bleed as in the present study.
Title: Widespread use of proton pump inhibitors or potassium-competitive acid blocker has
changed the status of gastrointestinal bleeding in patients with ischemic heart disease: Real-
world data from high volume centers
Version: 2 Date: 28 Oct 2023
Reviewer's report:
A good study but with a relatively short follow up and being retrospective bears the limitations
of missing out important data.
The following points needs clarification from the authors
[1] Please define severity grading of anemia, chronic kidney disease, cerebrovascular disease
[mild moderate severe etc]. Was it done by level of hemoglodin, GFR and type of CVA?
[2] It appears that patients of GI bleed included in study were severe ones [“that required
endoscopic hemostasis, hospitalization or blood transfusion, or fatal gastrointestinal bleeding”]
Were mild GI bleed that stopped by itself excluded? That would underestimate the risk or
incidence of GI bleed. This may be the reason why incidence of GI bleed is so small.
[3] Table 1. All odds ration are not mentioned. Please calculate them for all parameters. Compare
the haemoglobin and Prothrombin times of both groups in table. [It is likely that P.times must
have been done in most patients as they were on anticoagulants/antiplatelet agents.]. Hemoglobin
may be a surrogate for bleeding. Also mention the comorbidities and use of other medications
like steroids/NSAIDs and compare them in the two groups.
[4] Table 2. It should be mentioned whether any combination of PPI and PCAB were being
used. Similarly how many were using combinations of DAPT, DOAC, warfarin etc. All odds
ratio should be mentioned.
[5] It is only mentioned about endoscopic hemostasis in the paper. Did all bleeding patients
undergo endoscopy?  How was small intestinal pathology diagnosed?
[6] In the discussion section it is mentioned “Although we found some statistically significant
factors associated with gastrointestinal bleeding, they might be the result of type II errors due to
the very small number of gastrointestinal bleeding cases. Therefore, multicenter or prospective
studies are necessary to obtain more accurate data.” In this context the long term prospective
study “Incidence and outcome of gastrointestinal bleeding in patients receiving aspirin with or
without clopidogrel over 10 years - An observational study. December 2022, Journal of Family
Medicine and Primary care.” can be quoted which is a study with follow up of 10 years and
derives many of the factors associated with GI bleed on long term. The study is also relevant
for the sites of bleed as in the present study.
Please review this paper.
user
Title: Widespread use of proton pump inhibitors or potassium-competitive acid blocker has
changed the status of gastrointestinal bleeding in patients with ischemic heart disease: Real-
world data from high volume centers
Version: 2 Date: 28 Oct 2023
Reviewer's report:
A good study but with a relatively short follow up and being retrospective bears the limitations
of missing out important data.
The following points needs clarification from the authors
[1] Please define severity grading of anemia, chronic kidney disease, cerebrovascular disease
[mild moderate severe etc]. Was it done by level of hemoglodin, GFR and type of CVA?
[2] It appears that patients of GI bleed included in study were severe ones [“that required
endoscopic hemostasis, hospitalization or blood transfusion, or fatal gastrointestinal bleeding”]
Were mild GI bleed that stopped by itself excluded? That would underestimate the risk or
incidence of GI bleed. This may be the reason why incidence of GI bleed is so small.
[3] Table 1. All odds ration are not mentioned. Please calculate them for all parameters. Compare
the haemoglobin and Prothrombin times of both groups in table. [It is likely that P.times must
have been done in most patients as they were on anticoagulants/antiplatelet agents.]. Hemoglobin
may be a surrogate for bleeding. Also mention the comorbidities and use of other medications
like steroids/NSAIDs and compare them in the two groups.
[4] Table 2. It should be mentioned whether any combination of PPI and PCAB were being
used. Similarly how many were using combinations of DAPT, DOAC, warfarin etc. All odds
ratio should be mentioned.
[5] It is only mentioned about endoscopic hemostasis in the paper. Did all bleeding patients
undergo endoscopy?  How was small intestinal pathology diagnosed?
[6] In the discussion section it is mentioned “Although we found some statistically significant
factors associated with gastrointestinal bleeding, they might be the result of type II errors due to
the very small number of gastrointestinal bleeding cases. Therefore, multicenter or prospective
studies are necessary to obtain more accurate data.” In this context the long term prospective
study “Incidence and outcome of gastrointestinal bleeding in patients receiving aspirin with or
without clopidogrel over 10 years - An observational study. December 2022, Journal of Family
Medicine and Primary care.” can be quoted which is a study with follow up of 10 years and
derives many of the factors associated with GI bleed on long term. The study is also relevant
for the sites of bleed as in the present study.
assistant