Dataset Information

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study.

ABSTRACT:

Study question

What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?

Methods

This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models.

Study answer and limitations

The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding.

What this study adds

In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used.

Funding, competing interests, data sharing

AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.

SUBMITTER: Schjerning Olsen AM

PROVIDER: S-EPMC4609736 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment. Objectives:To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk. Design, Setting, and Participants:Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015. Exposures:Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy. Main Outcomes and Measures:Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10?000 person-years of anticoagulant treatment, incidence rate ratios (IRRs). Results:There were 1?643?123 patients with 1?713?183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651?427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870?330 person-years [74.9%]). During 754?389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n?=?7119) was 115 per 10?000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n?=?1278) was 144 per 10?000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n?=?279; 73 per 10?000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n?=?629; 120 per 10?000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n?=?4933; 113 per 10?000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, -47.5 [95% CI,-60.6 to -34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, -40.5 [95% CI, -50.0 to -31.0]). When anticoagulant treatment with PPI cotherapy (264?447 person-years; 76 per 10?000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n?=?2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, -24 [95% CI, -38 to -11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, -61.1 [95% CI, -74.8 to -47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, -35.5 [95% CI, -48.6 to -22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, -39.3 [95% CI, -44.5 to -34.2]). Conclusions and Relevance:Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.