How Common Is Gastrointestinal Bleeding in Patients Taking Multiple Antithrombotic Agents?

The use of more than one antithrombotic agent is increasing with the number of individuals living with one or more cardiovascular diseases. Particularly in older adults, weighing efficacy against bleeding risk is difficult because rates of gastrointestinal (GI) bleeding events with complex antithrombotic therapy are largely unknown. These investigators used data from a national pharmacy database to assess rates of GI bleeding events in 78,133 veterans aged 60–99 prescribed anticoagulants, antiplatelets, or aspirin in any combination of ≥2 during a 6-year period (2002–2008). They linked prescription-fill data to Veterans Administration and Medicare encounter files, assessed each person-day of follow-up for multiple-antithrombotic exposure, and defined outcomes according to diagnostic-code algorithms derived from chart abstraction.

Antiplatelets were prescribed with aspirin or an anticoagulant in 64% of patients, and triple therapy was prescribed in 6%. Incidence of upper- and lower-GI events was 20.1 and 70.1 per 1000 patient-years, respectively. Incidences of transfusion and hospitalization were highest with triple therapy and with aspirin–anticoagulant therapy. In multivariate analysis, risk for upper-GI events was increased by 40% to 60% with all treatment combinations, compared with no multiple-antithrombotic exposure. The risk for lower-GI bleeding increased by 30% with anticoagulant–antiplatelet therapy, and transfusion risk increased sixfold with aspirin–anticoagulation and fivefold with triple therapy. The number needed to harm for upper-GI events ranged from 52 (triple therapy) to 65 (anticoagulant–antiplatelet); the range for lower-GI events was 15 (aspirin–anticoagulant) to 23 (triple therapy); and the range for hospitalization was 34 (aspirin–anticoagulant) to 67 (aspirin–antiplatelet).