What is the cardiovascular risk of taking ibuprofen (Nonsteroidal Anti-Inflammatory Drug, NSAID)?

From the Guidelines

Ibuprofen increases the risk of myocardial infarction (MI), with a hazard ratio (HR) of 1.50 (1.36 to 1.67) for death, as reported in a study by Gislason et al. 1. The study analyzed the risk of rehospitalization for MI and death related to the use of NSAIDs, including selective COX-2 inhibitors, in patients with prior MI. The results showed that 17.5% of patients received ibuprofen, and the risk of death and rehospitalization for MI associated with the use of ibuprofen was significant. Key points to consider:

• The risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk in the patient 1.
• Nonpharmacological approaches are recommended as the first line of treatment, followed by a stepped-care approach to pharmacological therapy.
• Ibuprofen should not be used because it blocks the antiplatelet effects of aspirin, as stated in the 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction 1. Some important considerations:
• The risk of cardiovascular events associated with ibuprofen use is higher in patients with established cardiovascular disease or multiple risk factors.
• Even brief use of ibuprofen can increase risk in vulnerable populations.
• The cardiovascular effects of ibuprofen occur because it inhibits prostaglandin production, leading to sodium retention, increased blood pressure, and reduced kidney function, as well as affecting the balance between clot-promoting thromboxane and clot-preventing prostacyclin. In terms of specific numbers, the study by Gislason et al. found that 5.2% of patients received rofecoxib, 4.3% received celecoxib, 17.5% received ibuprofen, 10.6% received diclofenac, and 12.7% received other NSAIDs 1. The hazard ratios for death associated with the use of these medications were 2.80 (2.41 to 3.25) for rofecoxib, 2.57 (2.15 to 3.08) for celecoxib, 1.50 (1.36 to 1.67) for ibuprofen, 2.40 (2.09 to 2.80) for diclofenac, and 1.29 (1.16 to 1.43) for other NSAIDs. Overall, the use of ibuprofen is associated with a significant increase in cardiovascular risk, particularly in patients with established cardiovascular disease or multiple risk factors, as reported in the study by Gislason et al. 1.

From the FDA Drug Label

However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients.

The percentage of patients on ibuprofen who have an MI is not directly stated in the FDA drug label. However, it is mentioned that the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients, which includes those taking ibuprofen 2.

• Key points:
  • Increased risk of serious CV thrombotic events with ibuprofen use
  • Higher absolute incidence of excess serious CV thrombotic events in patients with known CV disease or risk factors
  • No direct percentage of patients on ibuprofen who have an MI is provided in the label.

From the Research

Cardiovascular Risk of Ibuprofen

The cardiovascular risk of taking ibuprofen, a Nonsteroidal Anti-Inflammatory Drug (NSAID), has been studied in various research papers.

• A study published in the Journal of Internal Medicine in 2008 found that the relative rate (RR) for myocardial infarction (MI) increased with cumulative and daily dose of ibuprofen 3.
• Another study published in Circulation in 2011 found that NSAID treatment, including ibuprofen, was significantly associated with an increased risk of death and recurrent MI in patients with prior MI 4.
• A systematic review of cohort and case-control studies on NSAIDs and myocardial infarction published in Basic & Clinical Pharmacology & Toxicology in 2006 found that the pooled relative risk of myocardial infarction was 1.07 for ibuprofen 5.
• A Bayesian meta-analysis of individual patient data published in the BMJ in 2017 found that taking any dose of ibuprofen for one week, one month, or more than a month was associated with an increased risk of myocardial infarction, with an odds ratio of 1.48 6.
• A nested case-control study published in the European Heart Journal in 2022 found that the risk of MI in ibuprofen users was concentrated in new PPI users, and there was no material increased risk in naproxen users, nor in past users of most NSAIDs in the absence of PPIs 7.

Percentage of Patients on Ibuprofen with MI

The exact percentage of patients on ibuprofen who experience a myocardial infarction (MI) is not directly stated in the provided studies.

• However, the studies suggest that the risk of MI is increased in patients taking ibuprofen, especially at higher doses and with longer durations of use.
• The odds ratios and relative risks reported in the studies can be used to estimate the increased risk of MI associated with ibuprofen use, but the actual percentage of patients experiencing an MI would depend on various factors, including the population being studied and the specific context of ibuprofen use.