Original article
Alimentary tract
Risk of Upper and Lower Gastrointestinal Bleeding in Patients Taking Nonsteroidal Anti-inflammatory Drugs, Antiplatelet Agents, or Anticoagulants

https://doi.org/10.1016/j.cgh.2014.11.007Get rights and content

Background & Aims

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants.

Methods

We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis.

Results

Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9–6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4–3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6–2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0–3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0–1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding.

Conclusions

Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding.

Section snippets

Study Design and Population

Case-control study with prospective case ascertainment and data collection was carried out between 2009 and mid-2013. Cases and controls were collected through a network of general hospitals integrated within the Spanish Association of Gastroenterology and the Biomedical Investigation Network Center of hepatic and digestive diseases (CIBERehd). Overall, eligible participants were 20–90 years old with non-variceal GI bleeding who had been free of liver disease, coagulation disorders, or

Demographics and Clinical Characteristics of Patients

A total of 1008 cases with GI bleeding and 1008 controls were collected from the participating centers. Men were 60.7% of cases and controls, and about 83.2% of the cases were aged >50 years. The mean age was 66.6 ± 16.0 and 65.6 ± 15.5 years in cases and controls, respectively. The corresponding figures for UGIB cases were 63.6 ± 16.7 years and for LGIB cases were 70.8 ± 13.8 years; also, 71.8% and 46.3% of patients, respectively, were men. Table 1 shows the frequency and crude estimate of RRs

Discussion

It is well-established that NSAIDs and ASA are associated with increased risk of UGIB,1, 2, 13, 14 but data on their effects on the risk of bleeding in lower GI tract are less clear, although the evidence has been growing in recent years.8, 9, 10 Also, the effect of non-aspirin APA drugs and anticoagulants on the risk of LGIB is much less explored. This study has evaluated the risk of GI bleeding associated with these compounds and compares the risks of either upper or lower GI bleeding in the

Acknowledgments

The authors thank the following people who helped in their work: M. A Aranguren, Hospital Donostia, San Sebastian, Spain; Judith Millastre, Hospital Universitario Miguel Servet, Zaragoza, Spain; Marta Gracia, Hospital Universitario Miguel Servet, Zaragoza, Spain; Ana Chaves, Hospital Costa del Sol, Marbella, Spain; Marta Ponce, Hospital La Fe, Valencia, Spain; Meritxell Sánchez-Lloansi, Corporació Sanitària Universitària, Sabadell, Spain; Pedro Lacarta, Hospital Clínico Universitario, Zaragoza,

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Conflicts of interest These authors disclose the following: L. A. García Rodríguez has received research funding from AstraZeneca R&D and Bayer and has also received honoraria for serving on scientific advisory boards for Bayer. The institution of Angel Lanas has received funds from Bayer for investigator-initiated research and Angel Lanas has been advisor to Pfizer and Bayer and received speaking fees from Bayer and AstraZeneca. The remaining authors disclose no conflicts.

Funding The study was funded by the Official Spanish Agency, Instituto de Salud Carlos III, FIS grant PI08/1301, and the CIBERehd, which is supporting the salary of Patricia Carrera.

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