Skip to main content

by Dr. C. H. Weaver M.D. Updated 09/21

The results of the PRECISION trial were published in the New England Journal of Medicine in the last issue of 2016.1 The clinical trial took 15 years from inception to publication. The findings of the study appear to describe a decade and a half of unwarranted concern about the use of Celecoxib in individuals with arthritis.

At the completion of the study, the number of events in patients who remained on the study drugs was 134 (1.7%), 144 (1.8%), and 155 (1.9%) patients on celecoxib, naproxen, and ibuprofen, respectively. The risk of gastrointestinal bleeding occurred at a lower rate for celecoxib than naproxen and ibuprofen. Decreased kidney events were similar for celecoxib and naproxen, but not ibuprofen.

Rheumatologists have been faced with the dilemma of how to treat patients with arthritis with the most effective and safe medicines. In the setting of an individual with minimal discomfort and dysfunction, the safest medicine seems to be the best choice. But what is the choice when significant pain causes decreased function? As joint pain causes increasing inability to do activities of daily living and exercise, other organs in the body suffer like the cardiovascular system. Inability to exercise can result in weight gain and hypertension which are detrimental to cardiovascular health. In that circumstance, consideration may be given to a drug that has greater power to decrease pain and improve function although the drug may be associated with a small increased risk of hypertension and cardiovascular events, like heart attack or stroke.

Prostaglandins are fatty acids products that are important for a number of bodily functions. Cyclooxygenases are enzymes that make prostaglandins from fatty acids in the membranes of our cells. Cycloooxygenase I (COX 1) is present all the time and does housekeeping chores like promoting mucous for the lining of our stomachs to protect from gastric acid and maintenance of blood flow to the kidneys. Cyclooxygenase II (COX 2) is generated in the setting of tissue injury and inflammation. Nonselective nonsteroidal anti-inflammatory drugs like ibuprofen and naproxen affect both enzymes. Selective COX 2 inhibitors, like celecoxib, are theoretically able to decrease pain without affecting the household chores of COX 1. A concern is the potential detrimental effect on blood flow and clotting in blood vessels causing heart attacks. Theoretically, if one prescribed a COX 2 inhibitor, the benefit would be pain relief without increased risk of gastrointestinal bleeding, but a possible increased risk of heart attack.

The PRECISION trial was designed to determine the degree of increased risk of clotting of blood vessels around the heart resulting in heart attacks associated with a COX-2 inhibitor (Celecoxib) versus non-selective (COX-1 and COX2 inhibitors) like Naproxen and Ibuprofen. Secondary outcomes measured the number of gastrointestinal bleeds and episodes of decreased renal function. A total of 24,881 patients were randomly assigned to celecoxib (8072), naproxen (7933) and ibuprofen (7990). The study was completed when enough heart attacks and strokes occurred to tell the difference between the groups. It took over a decade because there were so few events in every group.

The study has a number of limitations that make it difficult to make it pertain to clinical practice. The dose of celecoxib was below the 400 mg frequently prescribed for patients with rheumatoid or osteoarthritis. Will the higher dose for a prolonged period of time increase the risk? Other frequently prescribed NSAIDs, like diclofenac and meloxicam, were not included. Diclofenac has a higher risk for cardiovascular events but to what degree?

Scroll to Continue



Treating Autism: How Omega-3 Fish Oil Helps

Reduced social contact and the performance of repetitive activities are two behavioral traits that are altered in the neurodevelopmental condition known as an autism spectrum disorder (ASD).


Collagen Peptide Daily Digestion Guidelines

The amino acids included in collagen are crucial for its healing, which helps to rebuild and strengthen the lining of our digestive tract.


Top 3 Private Home Nurse Caregiving Benefits

A specialized method of looking after and caring for ourselves or our loved ones is through private duty nursing services. Keep reading to learn the benefits.

Was there evidence that demonstrated decreased cardiovascular risk for Celecoxib than this study published in 2016? In fact, evidence was available in 2004 that celecoxib had a decreased risk of acute heart attack compared to other NSAIDs. This information was included as a memorandum presented to the FDA in 2004.2

A large number of arthritis patients were made anxious unnecessarily concerning the use of celecoxib for their joint pain for over a decade. They thought they had to make a decision about what was most important, their joints or their heart.

The decision to use a specific therapy needs to be based upon your individual characteristics. That choice needs to be made between the patient and physician, deciding which intervention offers the best outcome for efficacy and safety.


  1. Nissen SE, Yeomans ND, Solomon DH et al. Cardiovascular safety of Celecoxib, Naproxen, or Ibuprofen for arthritis. NEJM 2016;375:2519-29
  2. Graham DJ, Memorandaum “Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated with COX-2 Selective and Non-Selective NSAIDs. September 30, 2004