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

CMAJ. 2011 Nov 8;183(16):1835-43. doi: 10.1503/cmaj.100912. Epub 2011 Sep 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Age Factors
  • Aged
  • Anemia / epidemiology
  • Angioplasty
  • Anticoagulants / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Canada / epidemiology
  • Citalopram / administration & dosage
  • Citalopram / adverse effects
  • Clopidogrel
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Fluoxetine / administration & dosage
  • Fluoxetine / adverse effects
  • Fluvoxamine / administration & dosage
  • Fluvoxamine / adverse effects
  • Heart Failure / epidemiology
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control*
  • Neoplasms / epidemiology
  • Paroxetine / administration & dosage
  • Paroxetine / adverse effects
  • Peptic Ulcer / epidemiology
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Renal Insufficiency / epidemiology
  • Retrospective Studies
  • Risk
  • Risk Factors
  • Secondary Prevention
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Sertraline / administration & dosage
  • Sertraline / adverse effects
  • Sex Factors
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives

Substances

  • Adrenal Cortex Hormones
  • Anticoagulants
  • Antihypertensive Agents
  • Hypoglycemic Agents
  • Platelet Aggregation Inhibitors
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Paroxetine
  • Clopidogrel
  • Fluvoxamine
  • Ticlopidine
  • Sertraline
  • Aspirin