Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction

Abstract

Background: Patients prescribed antiplatelet treatment to prevent recurrent acute myocardial infarction are often also given a selective serotonin reuptake inhibitor (SSRI) to treat coexisting depression. Use of either treatment may increase the risk of bleeding. We assessed the risk of bleeding among patients taking both medications following acute myocardial infarction.

Methods: We conducted a retrospective cohort study using hospital discharge abstracts, physician billing information, medication reimbursement claims and demographic data from provincial health services administrative databases. We included patients 50 years of age or older who were discharged from hospital with antiplatelet therapy following acute myocardial infarction between January 1998 and March 2007. Patients were followed until admission to hospital due to a bleeding episode, admission to hospital due to recurrent acute myocardial infarction, death or the end of the study period.

Results: The 27,058 patients in the cohort received the following medications at discharge: acetylsalicylic acid (ASA) (n = 14,426); clopidogrel (n = 2467), ASA and clopidogrel (n = 9475); ASA and an SSRI (n = 406); ASA, clopidogrel and an SSRI (n = 239); or clopidogrel and an SSRI (n = 45). Compared with ASA use alone, the combined use of an SSRI with antiplatelet therapy was associated with an increased risk of bleeding (ASA and SSRI: hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08-1.87; ASA, clopidogrel and SSRI: HR 2.35, 95% CI 1.61-3.42). Compared with dual antiplatelet therapy alone (ASA and clopidogrel), combined use of an SSRI and dual antiplatelet therapy was associated with an increased risk of bleeding (HR 1.57, 95% CI 1.07-2.32).

Interpretation: Patients taking an SSRI together with ASA or dual antiplatelet therapy following acute myocardial infarction were at increased risk of bleeding.

Figure 1:

Selection of patients for the study. ASA = acetylsalicylic acid, SSRI = selective serotonin reuptake inhibitor.

Figure 2:

Association between exposure to medications under study and risk of bleeding among patients taking antiplatelet therapy following acute myocardial infarction (Cox regression model with time-dependent exposure). The model was adjusted for patient characteristics presented in Figure 3. Hazard ratios greater than 1.0 indicate an increased risk of bleeding. ASA = acetylsalicylic acid, CI = confidence interval, HR = hazard ratio, SSRI = selective serotonin reuptake inhibitor.

Figure 3:

Patient characteristics associated with the risk of bleeding during follow-up (Cox regression model with time-dependent exposure). The model was adjusted for exposure to study drugs as presented in Figure 2, and for use of antidepressants other than selective serotonin reuptake inhibitors (SSRIs), use of Hp-PAC to treat Helicobacter pylori infection in year before index admission, use of antiplatelet agents other than acetylsalicylic acid (ASA) and clopidogrel in year before index admission, and use of gastroprotective agents (proton pump inhibitors and histamine-2 receptor antagonists). A hazard ratio greater than 1.0 indicates an increased risk of bleeding. CI = confidence interval, HR = hazard ratio. *Bleeding other than gastrointestinal bleeding or hemorrhagic stroke during the year before the index admission.