Nonsteroidal anti-inflammatory drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common class of analgesics used chronically for persistent pain due to osteoarthritis and other musculoskeletal disorders in older adults. Specifically, an estimated 40% of people age 65 years and older fill one or more prescriptions for a NSAID each year. Considering that NSAIDs are also currently available over the counter, it is clear to see that even larger numbers of older adults are exposed 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 only ADRs affecting these four organ systems are being discussed in this review, it is important to recognize that NSAIDs can cause various other adverse effects (eg, hepatotoxicity (liver damage), cutaneous toxicity).

GI Risks Associated with Chronic NSAID Use

The spectrum of potential NSAID-related GI adverse effects is wide, 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 have shown that the risk of peptic ulcer complications is increased by three- to fivefold in older adults using NSAIDs. This risk is much more pronounced in those taking concomitant systemic corticosteroids and warfarin. In addition, the risk is increased as early as within the first month of treatment and is sustained 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 negative 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 was increased nearly twofold for all NSAIDs within 30 days of initial use/prescribing. This risk is further increased 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 have been shown to worsen/increase the risk of various CV and cerebrovascular outcomes.

NSAIDs have also been shown to 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 has been shown to be associated with a number of CNS effects including aseptic meningitis, psychosis, and cognitive dysfunction. At the time of this writing, the 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 actually increase the risk of cognitive impairment. In particular, indomethacin appears to cause more CNS effects than other NSAIDs in the elderly.

Conclusion

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 only ADRs affecting these four organ systems were discussed 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 an important public health issue.

 

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