NSAIDs Double the Risk of Dangerous Blood Clots

nsaids mechanism neck pain relief side effects blood clotsUsing NSAIDs to manage chronic neck pain could almost double your risk of venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism, according to new research published in the journal Rheumatology. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a popular prescription and over-the-counter remedy for relief of inflammation and pain but these drugs are far from safe, especially when used for chronic conditions.

The new meta-analysis looked at published observational studies in order to assess the association between NSAID use and these dangerous types of blood clot. Six studies met their inclusion criteria, with 21,401 VTE events assessed. The researchers, working at the Bassett Medical Center and Columbia University College of Physicians and Surgeons, New York City, found that a statistically significantly increased VTE risk among NSAID users and noted that physicians should be aware of this increased risk, especially if prescribing NSAIDs to people whose risk of dangerous blood clotting is already high.

Double the Risk of Potentially Fatal Blood Clots

Venous thromboembolism (VTE) is, thankfully, relatively rare, which is why these researchers had to use observational studies (VTE occurs rarely in clinical trials). They included 1 cohort study involving 19,293 people and 215 VTEs, and 5 case-control studies involving 21,186 cases, along with 110,824 controls. Studies took place in the United Kingdom, France, the Netherlands, Denmark, and Sweden between 2007 and 2013.

Compared to non-users of NSAIDs, users had a 1.8-fold risk of venous thromboembolism. Those using selective cyclooxygenase 2 (COX-2) inhibitors had a 1.99-fold risk. COX-1 inhibitors, like aspirin, have actually been seen to effectively prevent VTE, so the increased risk of this potentially fatal complication likely stems from the use of COX-2 inhibitors.

How COX-2 Inhibitors Work

COX-2 inhibitors prevent the synthesis of prostacyclins but stimulate thromboxane release. Prostacyclins are potent inhibitors of platelet activation and thromboxanes are potent facilitators of platelet aggregation in active platelets.

The potential for adverse events with the use of COX-2 inhibitors has actually been known for many years. In fact, rofecoxib (commonly known as Vioxx) was removed from the market in 2004 because research revealed a significant increase in heart attacks and strokes in those taking this particular NSAID. Other NSAIDs such as celecoxib have since had to display warnings on their labels regarding the risk of stroke and heart attack.

The benefits of COX-2 inhibitors for pain from conditions such as arthritis have been well documented in clinical trials, but the potential doubling of the risk of blood clots may have people with chronic pain conditions thinking twice about using celecoxib and rofecoxib.

Natural Pain Relief

Alternative pain relief options do exist, including natural inhibitors of COX-2 enzymes that do not appear to increase the risk of VTE when taken at their recommended dosage (although further study is certainly warranted to get a clearer picture of this risk).

Such ‘natural NSAIDs’ include:

  • Turmeric (or, rather, curcumin, a compound found in turmeric)
  • Thunder God Vine
  • Omega 3 fatty acids (from fish oil, algal oil and flaxseed oil)
  • Resveratrol (a phytochemical found in red grape skins)
  • Genistein (an isoflavone found in soybeans)
  • Quercetin (found in apples, garlic, onions and other plants)

Excessive consumption of fish (more than 46g a day) does appear to increase the risk of stroke, but at lower doses omega 3 from fish oil actually reduces the risk of stroke while offering relief from pain and inflammation. Curcumin and resveratrol appear to thin the blood and reduce platelet aggregation, thereby reduce the risk of blood clots and stroke. These natural pain relief products could, however, increase the risk of problematic bleeding and should be discontinued at least a week prior to elective surgery.

NSAIDs may remain popular for treating chronic neck pain and other pain conditions but they are typically contraindicated after surgery involving fusion as they can decrease healthy bone growth. They also pose a risk of liver damage and gastrointestinal upset. Anyone using NSAIDs such as celecoxib for chronic neck pain should consult their physician to discuss alternative options if they are concerned about the risk of dangerous blood clots and stroke.


Ungprasert P, Srivali N, Wijarnpreecha K, Charoenpong P, Knight EL. Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis. Rheumatology (Oxford). 2014 Sep 24. pii: keu408. [Epub ahead of print]

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