SSRIs with oral anticoagulants increase bleeding risk in AF

Keep a close eye on patients in the first few months of concomitant use, research suggests.

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Combined use of SSRIs and oral anticoagulants in patients with atrial fibrillation increases the risk of major bleeding compared with OACs alone, Canadian researchers have found. 

Their case-controlled study, published in JAMA Network Open, included 42,000 AF patients who were on anticoagulant therapy and had been hospitalised with a major bleed.  

On analysing these patients’ use of SSRIs and comparing this with controls, the researchers found concomitant use of SSRIs and OACs appeared to increase the risk of major bleeding by 33% compared with using OACs alone.  

The risk was highest during the first 30 days of concomitant use, where it was almost doubled. The risk didn’t vary with age, sex, history of major bleeding, chronic kidney disease or potency of SSRIs. 

When looking at concomitant use of SSRIs and direct OACs versus vitamin K inhibitors, there was increased risk of a major bleed with both types of OACs. The risk with DOACs was numerically lower than for vitamin K inhibitors, but there was no statistically significant difference. 

Concomitant use of SSRIs and OACs is not uncommon among patients with atrial fibrillation. While SSRIs are known to increase the risk of major bleeding, the overall risk is low for most people. However, there has been concern that, when combined with OACs, the risks could be considerably greater, yet up now little has been known about the risks. 

Professor Jamie Vandenberg, deputy director of the Victor Chang Cardiac Research Institute, said the study was an interesting one, and he wasn’t aware of an increased risk of major bleeding when taking SSRIs with OACs. 

“I think the most important message to get out is that it’s still important to take your anticoagulants if you’ve got atrial fibrillation, because the risk of having a stroke if you’re not taking them is greater than the risk of having a bleed if you do take them,” he told The Medical Republic. 

“And they weren’t saying, you can’t take SSRIs if you’re on anticoagulants – they’re saying just be aware that there could be a slightly increased risk.” 

OACs included in the study were apixaban, dabigatran, edoxaban, rivaroxaban and warfarin. Prescriptions of SSRIs included citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. 

Altogether there were 330,000 patients with atrial fibrillation taking OACs, with the 42,000 cases who were hospitalised with major bleeding corresponding to an incident rate of 27.9 per 1000 person-years. 

In terms of types of major bleeding, the association was present for intracranial haemorrhage, gastrointestinal bleeding and other major bleeding.  

“Although the increased risk of major bleeding does not suggest withholding treatment with either SSRIs or OACs, measures can be taken to mitigate this risk,” the authors wrote. 

“Studies suggest that DOACs have lower potential for pharmacokinetic interactions with SSRIs than VKAs, and guidelines also recommend them over VKAs for the management of nonvalvular AF. Taken together with the findings in this study, DOACs may also be preferred for patients concomitantly using SSRIs.” 

The authors also pointed out that co-prescription of proton pump inhibitors has been suggested to prevent gastrointestinal bleeding.  

“Overall, risk factors for bleeding should be monitored and managed to improve the safety of the concomitant use of SSRIs and OACs. Close monitoring is particularly essential within the first few months of concomitant use,” they wrote. 

Professor Vandenberg pointed out that being a real-world study based on data collected in databases, there were bound to be errors in recording which could affect the quality of information, which the authors acknowledged. 

However, he said, the numbers were “very impressive” and using real-world data which takes on “all-comers”, as opposed to clinical trial data, has benefits in its applicability to the general population. 

“The main message is that these are both classes of drugs that are very useful for managing the conditions that they’re prescribed for, so it’s not uncommon that they’re co-prescribed,” Professor Vandenberg told TMR. 

“So the sensible thing is just to be careful and make sure that you’re aware of that potential increased risk of bleeding in that first few months.”  

JAMA Network Open 2024, online 22 March