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Risks of Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard class of drugs. They are used chronically for persistent pain due to osteoarthritis and other musculoskeletal disorders in older adults. Specifically, an estimated 40% of people age 65 and older fill one or more prescriptions for an NSAID each year. Exposing themselves to serious risk. Considering that NSAIDs are also currently available over the counter, it is clear to see that even more significant numbers of older adults expose themselves to NSAIDs in the United States.

NSAID use causes an estimated 41,000 hospitalizations and 3300 deaths each year among older adults.

Some specific ADRs of concern with chronic use of NSAIDs include:

  1. Gastrointestinal (GI)
  2. Renal
  3. Cardiovascular (CV – heart attacks or heart failure) and cerebrovascular (strokes)
  4. Central nervous system (CNS – dementia, cognitive impairment)

Although I only discuss ADRs affecting these four organ systems in this review, it is crucial to recognize that NSAIDs can cause various other adverse effects (e.g., hepatotoxicity (liver damage), cutaneous toxicity).

GI Risks Associated with Chronic NSAID Use

The spectrum of potential NSAID-related GI adverse effects is extensive, ranging from dyspepsia to life-threatening gastric bleeding. A nested case-control study showed that NSAIDs increase the risk of fatal peptic ulcers by nearly fivefold in older adults. Other studies show that the risk of peptic ulcer complications increases by three- to fivefold in older adults using NSAIDs. This risk higher in those taking concomitant systemic corticosteroids and warfarin. In addition, the risk is increased as early as within the first month of treatment and sustains over time. Often, these peptic ulcers are asymptomatic but can lead to significant morbidity and mortality.

Renal Risks Associated with Chronic NSAID Use

Similar to NSAID-related GI adverse effects, NSAID-induced renal dysfunction has a wide spectrum of adverse effects, including decreased glomerular perfusion, decreased glomerular filtration rate, and acute renal failure (ARF). While it is important to recognize that ARF can develop at any point during long-term NSAID therapy, the risk may be highest among those who have recently initiated therapy.

Specifically, in a nested case-control study of older adults, the risk of ARF increases nearly twofold for all NSAIDs within 30 days of initial use/prescribing. This risk is greater in those older adults with pre-existing chronic kidney disease (CKD) and in those who use long half-life NSAIDs.

Cardiovascular/Cerebrovascular (heart attack/stroke) Risks Associated with Chronic NSAID Use

NSAIDs worsen/increase the risk of various CV and cerebrovascular outcomes.

NSAIDs =also cause or exacerbate heart failure (HF) in older adults. Specifically, a cohort study of older adults found that rofecoxib and nonselective NSAIDs (naproxen, ibuprofen, and diclofenac), but not celecoxib were significantly associated with an increased risk of admission for HF as compared to those not taking NSAIDs. Another cohort study found that among patients who had survived their first hospitalization because of HF. Subsequent use of any NSAID (including celecoxib, as well as ibuprofen, diclofenac, naproxen, and other NSAIDs) led to a significantly increased risk of death.

CNS (Central Nervous System) Risks Associated with Chronic NSAID Use

NSAID use is associated with several CNS effects, including aseptic meningitis, psychosis, and cognitive dysfunction. Studies to date have not consistently shown a benefit from chronic NSAID use in reducing the risk of dementia or cognitive impairment. Interestingly, though, several studies have shown that high-dose NSAIDs (i.e., anti-inflammatory doses) may increase the risk of cognitive impairment. In particular, indomethacin appears to cause more CNS effects than other NSAIDs in the elderly.


This review has summarized the potential risks associated with chronic NSAID use in older adults. Including GI, renal, CV/cerebrovascular, and CNS adverse effects. Although I only discuss ADRs affecting these four organ systems in this review, it is important to recognize that NSAIDs can cause various other adverse effects (eg, hepatotoxicity, cutaneous toxicity). Moreover, it is important to note that nonpharmacological approaches (weight reduction, increasing physical activity) may also help patients who are experiencing musculoskeletal pain.

As the aging population rapidly grows over the next few decades, the risks associated with chronic NSAID use will remain a significant public health issue.