Combining NSAIDs and Anticoagulation

NSAIDs are anti-inflammatory medications. The most common reasons to take them are chronic joint pain. Unfortunately, many patients who require anticoagulation also need NSAIDs. The question that usually comes up is whether combining NSAIDs and anticoagulation will increase bleeding risk. Here is some of the data.

Why would Combining NSAIDs and Anticoagulation Increase Bleeding Risk?

In theory, both NSAIDs and anticoagulation can cause bleeding. But, each does this in a different mechanism. NSAIDs can cause bleeding by inhibiting platelet function and by promoting gastric bleeding. There are even some data to suggest lower gastrointestinal bleeds with some NSAIDs. Obviously, anticoagulation can cause bleeding through their effect on clotting factors.

So, the concern is that combining the two can result in a bleed through one mechanism that is exacerbated by the other.

There is some evidence for this. A Danish group published about increased bleeding in atrial fibrillation patients and in myocardial infarction patients who received NSIADs. In fact, bleeding was higher even after short-term use. Combining NSAIDs and anticoagulation doubled the risk for bleeding. While the overall “crude” risk was not very high, it was not negligible either (4.2 per 100 person-years). These data are especially pertinent to myocardial infarction patients. A previous paper showed that even short-term NSIADs could increase overall mortality in these patients.

There are data that show that NSAIDs increase bleeding risk in combination with both Warfarin and DOAC. These data seem to repeat themselves across multiple studies. The data also seem to repeat themselves when the anticoagulation is for venous thromboembolism.

Not all NSAIDs are the Same

There are ways to reduce NSAID-related gastrointestinal bleeding. The first, is to prescribe a proton pump inhibitor. Combining a proton pump inhibitor with an NSAID can reduce bleeding risk. But a second way is to choose NSAIDs that have a lower bleeding risk. Typically, these are COX-2 specific inhibitors. The idea is that these do not affect the gastric lining as much as non-specific NSAIDs.

The effect of various NSAIDs on platelet function is also not uniform. For instance, Meloxicam does not inhibit platelet function enough to cause in vivo bleeding alterations.

Still, a meta-analysis showed that combining all types of NSAIDs and anticoagulation with Warfarin resulted in excess bleeding.

Not all Patients are the Same

When it comes to bleeding risk, not all patients are the same. Some patients have a higher bleeding risk than others. Unfortunately, it is often hard to assess a specific patient’s bleeding risk. But there are a few factors that we can look for:

• A known risk for bleeding. For instance, peptic Ulcer disease.
• Previous bleeding
• Platelet abnormality
• Renal or liver function abnormality
• Older age (compared to younger age)
• Inconsistent anticoagulation. For instance, in patients who are taking Coumadin, labile INR signify a bleeding risk. Another example is surgery and blood thinners. Basically, the post-surgical time is a time of problematic anticoagulation but also a time when patients sometimes need NSAIDs for pain control.

Of course, there are scores that help us assess bleeding risk. For example, the famous HAS-BLED score. But these scores were calibrated for a particular reason. Using them to assess the risk of combining NSAIDs and anticoagulation may not be accurate.