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SSRIs associated with 40% increase in bleeding risk when used with aspirin

GPs have been advised to show caution when prescribing SSRIs in patients taking aspirin following an acute myocardial infarction, after an analysis showed an increased risk of bleeding.

SSRIs and antiplatelet agents - such as aspirin and clopidogrel – have been individually associated with increased risk of bleeding, but this Canadian study looked at the effect of combinations of these drugs in clinical practice.

The study looked retrospectively at data from 27,058 patients, aged 50 years or older, who were discharged from hospital after an acute myocardial infarction between January 1998 and March 2007.

Following discharge, 14,426 of the patients in the cohort took aspirin alone, while 406 took both aspirin and an SSRI. They found patients taking both aspirin and an SSRI had a 42% increased risk of a bleeding episode - gastrointestinal bleeding, hemorrhagic stroke or other bleeding that required hospital admission - compared with those taking aspirin alone.

The risk of bleeding among patients taking clopidogrel in combination with an SSRI was also higher than clopidogrel alone – with a hazard ratio of 1.54. However, the number of patients taking clopidogrel was not large enough to confirm the finding.

Combined use of clopidogrel and aspirin increased the risk of bleeding by 49% beyond that of aspirin alone, and using an SSRI in addition to this further increased the risk by 57%, compared with dual antiplatelet therapy alone.

An analysis of the risk of bleeding with other non-SSRI antidepressants did not find any substantially increased risk.

Antiplatelets are a ‘mainstay' of post-myocardial infarction care, and antidepressants are often prescribed to treat depression in patients with cardiovascular disease, but the authors of this study advised caution.

Study lead Dr Elham Rahme, assistant professor at McGill University, Montreal, Canada said: ‘Clinicians must weigh the benefits of SSRI therapy against the risk of bleeding in patients with major depression following acute myocardial infarction.'

Dr Ivan Benett, a GPSI in cardiology in Manchester, said: ‘This is a large paper but has the distinct limitation of being a retrospective cohort study. Nevertheless, it is interesting because it alerts us in primary care to the possible danger of prescribing these drugs together'

‘However, there may well be occasions when you have no choice but to be on both an SSRI and antiplatelet therapy, in which case combining SSRI with clopidogrel seems safest, and probably a wise course of action.'


How antiplatelets increase bleeding risk

Drug exposure                                  Hazard ratio

Aspirin (reference)                         1.0

Aspirin + SSRI                                     1.42

Clopidogrel                                         1.15

Clopidogrel + SSRI                            1.76

Aspirin + Clopidogrel                      1.49

Aspirin + Clopidogrel + SSRI         2.35

Source: Canadian Medical Association Journal 2011. Online 26 September.


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