Should PPIs be given to patients on antiplatelet drugs?

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Antiplatelet drug use is associated with an increased risk of upper gastrointestinal bleeding (UGIB); data on the impact of gastroprotective agents, such as PPIs, in this setting are, however, lacking.


To determine the risk of UGIB in patients on antiplatelet drugs and investigate the impact of gastroprotective agents.


This multicenter, case-control study included patients with acute UGIB of duodenal or gastric ulcer origin, erosive duodenitis, acute lesions of the gastric mucosa, or mixed lesions. Exclusion criteria included anticoagulant use and UGIB from any other source than those described above. Three control patients were matched to each eligible case of UGIB according to age, sex, and date of hospital admission. Matched controls were individuals admitted to hospital with acute clinical conditions not related to drug use, with trauma not related to alcohol use, or for elective surgery for a nonpainful disorder. Patients with UGIB and controls were interviewed and symptoms and a full medical history were recorded. The average daily dose of each antiplatelet drug (aspirin, clopidogrel, dipyridamole, indobufen, ticlopidine, and triflusal) was calculated and patients were subdivided into categories according to dose. The odds ratio (OR) for UGIB was estimated for each drug and patient variables such as history of peptic ulcer, use of NSAIDs, peptic ulcer disease, and history of UGIB were taken into consideration. The impact of the use of gastroprotective agents was determined for the study population and for subgroups with underlying risk, such as those with a history of peptic ulcer disease or UGIB.


The main outcome measures were incidence of UGIB and the OR for UGIB for each antiplatelet drug.


In total, 2,831 cases of UGIB and 7,193 matched controls were included in the study; 2,783 cases of UGIB and 7,058 matched controls were included in the final regression analysis. The OR for UGIB was 4.0 (95% CI 3.2-4.9) for acetylsalicylic acid, 2.3 (95% CI 0.9-6.0) for clopidogrel, 0.9 (95% CI 0.4-2.0) for dipyridamole, 3.8 (95% CI 1.2-12.2) for indobufen, 3.1 (95% CI 1.8-5.1) for ticlopidine, and 1.6 (95% CI 0.9-2.7) for triflusal. The concomitant use of PPIs reduced the OR for UGIB associated with aspirin and nonaspirin antiplatelet drugs from 4.0 (95% CI 3.2-4.9) to 1.1 (95% CI 0.5-2.6), and from 2.1 (95% CI 1.5-2.9) to 0.9 (95% CI 0.4-2.3), respectively. PPIs reduced the risk of UGIB across all patient categories of underlying risk. For example, inpatients with a history of peptic ulcer, the OR for UGIB was reduced from 8.6 (95% CI 5.3-12.9) to 3.0 (95% CI 0.9-9.4). Antiplatelet drugs are responsible for 14.5% of all UGIB cases.


The concomitant use of PPIs with antiplatelet drugs reduces the risk of UGIB. In patients using antiplatelet drugs and concomitant PPI therapy, the risk of UGIB seems lower with aspirin than with nonaspirin antiplatelet drugs.

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