Choosing the specific course of pharmacologic management for a patient with OA can be overwhelming given the number of options currently available. Acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitor NSAIDs, opioid analgesics, and various topical therapies have been shown to be efficacious in the management of OA pain.
4-6,8 Oral NSAIDs are commonly prescribed because of their established anti-inflammatory effects, clinical efficacy, and lack of addictive potential compared with opioids.
4-7 However, growing awareness of the gastrointestinal and cardiovascular adverse effects of oral NSAIDs and selective COX-2 inhibitors has raised the question of where these agents belong in the overall OA treatment paradigm, especially for patients with established cardiovascular disease or an elevated risk of gastrointestinal adverse events.
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The dose-related gastrointestinal adverse events associated with oral nonselective NSAIDs occur as a result of the inhibition of the COX-1 enzyme, which is responsible for normal gastroprotective processes.
15 Common gastrointestinal adverse events observed with these agents include dyspepsia (3% to 26%), abdominal pain (3% to 22%), and nausea (2% to 13%).
16 However, more serious adverse events can occur, including upper gastrointestinal bleeding, ulcerations, and death.
17 Oral nonselective NSAIDs have been shown to increase the risk of gastrointestinal complications in individuals already at high risk, including those older than 70 years, those with certain comorbid medical conditions (such as a history of peptic ulcer disease, gastrointestinal bleeding, or active
Helicobacter pylori infection), and those who take certain concurrent medications (such as corticosteroids and antiplatelet agents).
17,18
Oral nonselective NSAIDs are known to cause an increase in blood pressure, but until recently their impact on cardiovascular outcomes was not known. It is now well established that both oral nonselective and COX-2 selective NSAIDs increase the incidence of myocardial infarction, stroke, and death.
12,13,19 This risk can be compounded by the multitude of risk factors for cardiovascular disease, including cigarette smoking, increased age, and comorbid conditions (eg, diabetes mellitus, hyperlipidemia, hypertension).
20 The American Heart Association's guidelines on NSAID use suggest that the cardiovascular risks are associated only with chronic use or with higher doses of drugs in this class.
19 More recent evidence, however, suggests that the increase in risk is more rapid: a study of patients taking oral NSAIDs demonstrated that the risk of myocardial infarction increases after the first dose of certain oral nonselective NSAIDs and after 30 days for COX-2 selective NSAIDs.
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