What is the risk of ischemic stroke associated with Celebrex (Celecoxib)?

From the Guidelines

Celebrex (celecoxib) may increase the risk of ischemic stroke in some patients, particularly those with pre-existing cardiovascular disease or stroke risk factors. This medication belongs to the COX-2 inhibitor class of NSAIDs, which has been associated with increased cardiovascular risks including heart attack and stroke, as reported in a study by the American Heart Association 1. The risk appears to be dose-dependent, with higher doses (400mg daily or more) carrying greater risk than lower doses.

Key Considerations

• Patients with a history of stroke, heart disease, hypertension, diabetes, smoking, or high cholesterol should use Celebrex with caution and only after discussing risks with their healthcare provider.
• The stroke risk is thought to be related to COX-2 inhibitors' effects on the balance between thromboxane and prostacyclin, potentially promoting blood clotting and vasoconstriction, as explained in a study published in Clinical Gastroenterology and Hepatology 1.
• If Celebrex is prescribed, it should be used at the lowest effective dose for the shortest duration possible, as recommended by the American College of Cardiology/American Heart Association 1.
• Patients taking Celebrex should be vigilant for warning signs of stroke such as sudden numbness, confusion, trouble speaking, vision problems, dizziness, or severe headache, and seek immediate medical attention if these occur.

Evidence-Based Recommendations

• The American Heart Association recommends that COX-2 inhibitors, including Celebrex, be used with caution in patients at risk of cardiovascular events 1.
• A study published in Circulation found that the risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk in the patient 1.
• The FDA has issued a "black box" warning for Celebrex, highlighting the increased risk of cardiovascular events, including heart attack and stroke 1.

From the FDA Drug Label

1. Warnings and Precautions 5. 1 Cardiovascular Thrombotic Events Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction. In the APC (Adenoma Prevention with Celecoxib) trial, there was about a threefold increased risk of the composite endpoint of cardiovascular death, MI, or stroke for the celecoxib capsules 400 mg twice daily and celecoxib capsules 200 mg twice daily treatment arms compared to placebo A randomized controlled trial entitled the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION) was conducted to assess the relative cardiovascular thrombotic risk of a COX-2 inhibitor, celecoxib, compared to the non-selective NSAIDs naproxen and ibuprofen Celecoxib 100 mg twice daily was non-inferior to naproxen 375 to 500 mg twice daily and ibuprofen 600 to 800 mg three times daily for the composite endpoint of the Antiplatelet Trialists' Collaboration (APTC), which consists of cardiovascular death (including hemorrhagic death), non-fatal myocardial infarction, and nonfatal stroke

Celebrex and Ischemic Stroke:

• The use of celecoxib may increase the risk of serious cardiovascular thrombotic events, including ischemic stroke.
• Clinical trials have shown that celecoxib can increase the risk of stroke, particularly at higher doses.
• The PRECISION trial found that celecoxib 100 mg twice daily was non-inferior to naproxen and ibuprofen for the composite endpoint of cardiovascular death, non-fatal myocardial infarction, and nonfatal stroke.
• To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible 2.
• Patients should be informed about the symptoms of serious CV events and the steps to take if they occur 2.

From the Research

Celebrex and Ischemic Stroke

• The relationship between Celebrex (celecoxib) and ischemic stroke is complex, with some studies suggesting an increased risk of cardiovascular events, including stroke, associated with its use 3, 4.
• A meta-analysis of randomized controlled trials found a significantly higher incidence of serious vascular events, including non-fatal myocardial infarction, in patients treated with celecoxib compared to those receiving placebo 4.
• However, another study found that early use of celecoxib in patients with spontaneous intracerebral hemorrhage was associated with reduced mortality, with no significant increase in the risk of ischemic stroke or other cardiovascular events 5.
• The use of celecoxib may be associated with a small increase in the risk of cardiovascular events, including ischemic stroke, but the absolute risk is small, and the benefits of the drug may outweigh the potential adverse effects on the cardiovascular system 6, 7, 4.
• It is essential to weigh the potential gastrointestinal, cardiovascular, and renal risks of celecoxib against its benefits in each individual patient, and to use the lowest effective dose for the shortest possible duration 6, 7.