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Millions of Americans take anticoagulants (blood thinners) on a long-term basis to prevent the formation of potentially harmful clots in the heart, veins or arteries. These drugs offer great benefit by preventing devastating consequences of undesired clot formation, such as strokes, lung damage, limb loss and, in some cases, death.
However, these anti-clotting benefits of anticoagulants come at the price of an increased risk of potentially life-threatening bleeding. Thus, treatment...
Millions of Americans take anticoagulants (blood thinners) on a long-term basis to prevent the formation of potentially harmful clots in the heart, veins or arteries. These drugs offer great benefit by preventing devastating consequences of undesired clot formation, such as strokes, lung damage, limb loss and, in some cases, death.
However, these anti-clotting benefits of anticoagulants come at the price of an increased risk of potentially life-threatening bleeding. Thus, treatment with these drugs requires regular monitoring to strike a delicate balance between preventing harmful clots and avoiding dangerous bleeding. Many factors, including use of certain drugs that interact with anticoagulants, can tilt this balance in one direction or the other.
A recent study in the Journal of the American College of Cardiology (JACC) adds to the increasing body of evidence demonstrating that the concomitant use of oral anticoagulants and a commonly used class of pain medications known as nonsteroidal anti-inflammatory drugs (NSAIDs) can tip this benefit-risk balance unfavorably toward serious bleeding (for a list of available oral NSAIDs, see Table below). The study found that in patients with atrial fibrillation (a common type of abnormal heart rhythm that increases the risk of stroke), combining drugs from these two classes is associated with an increased risk of major bleeding, stroke, systemic embolism (blood clots that lodge in arteries) and hospitalization.[1]
About oral anticoagulants and NSAIDs
Coagulation or clotting is the process by which blood forms gel-like clumps, known as clots, and is often initiated by injury. Clots are crucial because they act as plugs at sites of injury, preventing further bleeding. However, unnecessary clots sometimes form in the heart or blood stream and then travel to different parts of the body, thereby blocking normal blood flow.
There are two essential components that are necessary for blood clot formation. Soluble clotting factors, which are made in the liver and circulate in the blood, must come together to form the basic building blocks and supporting framework of a clot. Then, a group of cell-like structures called platelets, which are produced in the bone marrow, must clump together with activated clotting factors to form a clot.
Blocking either clotting factors or platelet function interferes with clot formation. The oral anticoagulant warfarin (COUMADIN, JANTOVEN) is one of the oldest and most widely prescribed blood thinners. It works by interfering with the formation of multiple clotting factors. Dabigatran (PRADAXA) is one of several newer blood thinners that inhibit specific individual clotting factors and was approved with the promise of improved convenience and decreased monitoring requirements. We have designated dabigatran as Do Not Use because post-approval clinical experience showed an increase in bleeding events with its use.[2]
In contrast, NSAIDs interfere with clot formation by inhibiting platelet function. Therefore, the concomitant use of an NSAID and an anticoagulant can significantly increase the risk of bleeding because each drug targets a different component of the clotting process.
The new JACC study[3]
The study researchers analyzed data from a completed large clinical trial that randomly assigned subjects with atrial fibrillation to treatment with either dabigatran or warfarin. They further divided these subjects into one group that, in addition to taking one of the two oral blood thinners, also had used an NSAID at least once during the trial and another group that did not use any NSAID during the trial. Overall, there were 2,279 subjects in the first group and 15,834 in the second group. The proportion of subjects taking NSAIDs and dabigatran was similar to those taking NSAIDs and warfarin: 13 percent.
One of the main study outcomes was major bleeding. Bleeding was categorized as major if it was fatal, involved a significant drop in the red blood cell count on a blood test, occurred at a critical site (such as bleeding into the brain) or required a transfusion of two or more units of blood.[4] The researchers found that the annual rate of major bleeding was significantly higher in subjects with combined oral blood thinner and NSAID use than in those who took an oral anticoagulant alone, irrespective of the type of oral blood thinner taken.
Similarly, the rate of major bleeding in the stomach or intestines was significantly higher among subjects who took a blood thinner and an NSAID at least once during the study than in those who took an anticoagulant alone. This finding also was consistent between subjects who took dabigatran and those who took warfarin.
Additionally, ischemic stroke, which is caused by a clot that blocks blood flow to the brain, and hospitalization occurred more frequently with NSAID use. The stroke and systemic embolism rates were also higher in subjects taking both NSAIDs and anticoagulants than in those who only used anticoagulants, but the differences were not statistically significant. Rates of hemorrhagic stroke (stroke caused by bleeding into the brain) and heart attack were not affected by NSAID use.
There were several limitations to the study. First, the analysis was done after the large clinical trial was completed and was not planned when the study was originally designed, which could have biased the results. Second, the analysis evaluated whether or not NSAIDs were used, regardless of type of NSAID, dosage, duration and timing. Finally, the study failed to capture other baseline characteristics of the subject population, such as underlying inflammatory diseases, that would explain the use of NSAIDs.
The study researchers concluded that the use of NSAIDs in combination with oral anticoagulant therapy using either dabigatran or warfarin in subjects with atrial fibrillation is associated with increased risk of major bleeding, stroke, gastrointestinal major bleeding and hospitalization.
What You Can Do
You should avoid taking NSAIDs, including aspirin (BAYER, DURLAZA, ECOTRIN), for pain while taking blood thinners. Patients taking NSAIDs with blood thinners should consult with their primary care physician to make sure that the combination does not increase the risk of bleeding. Instead of using NSAIDs for pain relief, consult with your doctor to take other non-opioid pain relief medications that do not interfere with the clotting process.
List of Oral Nonsteroidal Anti-inflammatory Drugs
| Generic Name | Brand Name(s) |
|---|---|
| aspirin | BAYER, DURLAZA, ECOTRIN |
| diclofenac* | ARTHROTEC,** CAMBIA, ZIPSOR, ZORVOLEX |
| fenoprofen*** | NALFON |
| flurbiprofen | generic only |
| ibuprofen | ADVIL,† DUEXIS,** IBU-TAB, IBUPROHM,† MIDOL LIQUID GELS,† MOTRIN IB,† PROFEN,† REPREXAIN,** SINE-AID IB,**,† TAB-PROFEN† |
| indomethacin* | INDOCIN, TIVORBEX |
| ketoprofen | generic only |
| ketorolac* | generic only |
| naproxen | ALEVE,† ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN, TREXIMET,** VIMOVO** |
| piroxicam* | FELDENE |
| sulindac*** | generic only |
| tolmetin*** | generic only |
*Designated as Do Not Use
**Combination drug that contains at least one other active ingredient not listed
***Designated as Limited Use
†Over-the-counter product
References
[1] Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-Inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267.
[2] Emerging risks with new stroke prevention drugs. Worst Pills, Best Pills News. April 2013. /newsletters/view/843. Accessed December 26, 2018.
[3] Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-Inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267.
[4] Ezekowitz MD, Connolly S, Parekh A, et al. Rationale and design of RE-LY: Randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am. Heart J. 2009;157(5):805-810.
