Antiplatelet Therapy Plus SSRI Spurs Bleeding After MI

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Patients discharged on a selective serotonin reuptake inhibitor (SSRI) as well as antiplatelet therapy—whether aspirin, clopidogrel, or both—after myocardial infarction (MI) experience heightened bleeding risk compared with those not taking such antidepressants. The findings, from a retrospective cohort study, were published online September 26, 2011, ahead of print in the Canadian Medical Association Journal.

Prescribing clinicians should weigh the benefits of SSRI therapy against the risk of bleeding in MI patients with major depression, the authors conclude.

Bleeding from a New Perspective

Led by Elham Rahme, PhD, of Fonds de la Recherche en Santé du Québec (Quebec, Canada), the study retrospectively reviewed the administrative databases of provincial health services in Quebec from 1998 to 2007, looking at patients aged at least 50 years who had a primary diagnosis of acute MI (n = 27,058). Based on medications that were dispensed at discharge, patients were divided into 6 groups:

• Aspirin alone (n = 14,426)
• Clopidogrel alone (n = 2,467)
• Aspirin and clopidogrel (n = 9,475)
• Aspirin and SSRI (n = 406)
• Clopidogrel and SSRI (n = 45)
• Aspirin, clopidogrel, and SSRI (n = 239)

Approximately 3% of patients were taking an SSRI in combination with any antiplatelet therapy at discharge. The percentage of patients who received angioplasty as their index procedure ranged from 3.0% in patients receiving aspirin and an SSRI to 29.8% in those receiving dual antiplatelet therapy without an SSRI.

A total of 1,070 bleeding episodes occurred during 80,991 patient-years. Crude bleeding rates were higher in patients who took an SSRI in addition to antiplatelet therapy (table 1).

Table 1. Rate per 100 Patient-Years

Using a Cox regression model that accounted for length of exposure, the researchers found that SSRI augmented the risk of bleeding compared with aspirin alone (table 2).

Table 2. Likelihood of Bleeding

Adding an SSRI to clopidogrel also increased risk vs. clopidogrel alone (HR 1.54; 95% CI 0.70-3.39), as did adding an SSRI to dual antiplatelet therapy vs. aspirin and clopidogrel alone (HR 1.57; 95% CI 1.07-2.32).

The results did not vary by type of SSRI or when the researchers excluded patients taking drugs that could interact with clopidogrel (including proton pump inhibitors, sertraline, and fluoxetine). Importantly, the use of antidepressants other than SSRIs in conjunction with antiplatelet therapy did not increase bleeding risk.

Implications for Practice

Although the researchers acknowledge a number of limitations to their study, including its retrospective and observational nature, they stress that the results should inform physician decision making.

“Ultimately, clinicians must weigh the benefits of SSRI therapy against the risk of bleeding in patients with major depression following acute myocardial infarction,” Dr. Rahme and colleagues conclude. “Clinicians should exercise caution when prescribing SSRIs to their patients with major depression following myocardial infarction.”

Study Details 

Bleeding, the study’s primary outcome, was defined as gastrointestinal bleeding, hemorrhagic stroke, or any other bleeding episode that necessitated hospital admission or occurred in-hospital during follow-up. Patients were tracked until admission for bleeding, admission for recurrent MI, death, or the end of the study. 

Compared with those on aspirin alone, subjects receiving aspirin plus an SSRI tended to be older, have renal failure, have taken antihypertensive or antidepressant drugs in the year before index admission, and to currently be taking a corticosteroid. Compared with those on dual antiplatelet therapy, subjects who added an SSRI to that regimen were more likely to be older, have taken antihyperglycemic or antidepressant drugs in the year before index admission, and to have concurrent anemia or other hematologic disease.

  

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Source:
Labos C, Dasgupta K, Nedjar H, et al. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ. 2011;Epub ahead of print.

 

 

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