ReviewNon-steroidal anti-inflammatory drug use in the elderly
Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most commonly used medications worldwide for the treatment of pain and inflammation. Epidemiological data from the US reported that 70% of people aged 65 years or older used NSAIDs and/or aspirin at least once weekly and 34% at least daily [1]. In Europe, NSAIDs represent no less than 7.7% of all prescriptions [2]. Data from the Italian Minister of Health reported that in the year 2004 the prescriptions of NSAIDs made up 6.1% of all prescriptions, most of them for diseases of the musculoskeletal system, i.e. osteoarthritis (33%) and rheumatoid arthritis (2%), but also for the treatment of acute or chronic pain, independently from the presence of clinical signs of inflammation [3]. Since over-the-counter use of NSAIDs was not included, however, these rates certainly underestimate the overall use, particularly in old age [4].
Indeed, a multicentre study carried out in 3154 ambulatory elderly patients from Italy demonstrated that the prevalence of NSAID and/or regular dose aspirin use was 24.7%. NSAID and aspirin use was significantly higher in women than men (28.2% versus 19.3%, p < 0.0001). Moreover, classifying patients according to their drug use patterns, only 32.9% were chronic users, 24.9% were acute users and 42.1% of patients were occasional users [5].
More recently, a multicentre study carried out in 5515 subjects aged 65 years and older demonstrated that musculoskeletal drugs were taken by 15% of patients; NSAIDs and/or cyclo-oxygenase-2 inhibitors (coxibs) were taken by 9% of patients. NSAID and/or coxib use was higher in women than men (11.6% versus 6.0%, p < 0.0001) and was significantly associated with a moderate–severe grade of disability in the activities of daily living (ADL) [6].
Section snippets
Mechanisms of action of NSAIDs
The benefit of NSAIDs derives from their anti-inflammatory and analgesic effects mainly due to the inhibition of cyclo-oxygenase (COX), the enzyme that transforms arachidonic acid into prostaglandins and thromboxanes which are involved in inflammation, pain and platelet aggregation. Two isoforms of COX have been described. COX-1 is expressed in most tissues producing prostanoids, which are involved in the defence and repair of the gastrointestinal mucosa, platelet aggregation and thrombosis as
Gastrointestinal adverse events
It is well known that NSAID use is associated with a high risk of upper gastrointestinal symptoms and lesions such as oesophagitis, gastritis, peptic ulcers, and their severe complications including bleeding and perforation. NSAID use, moreover, is related to the presence of erosions and/or ulcers of the small and large intestine.
The injurious gastroduodenal effects of NSAIDs are mainly caused by the inhibition of COX-1 and its role in mucosal defence mechanisms and also through the inhibition
Cardiovascular thrombotic events
Several data suggest that the use of coxibs was associated with serious cardiovascular events [23], [24]. Emerging evidences, however, suggest that non-selective NSAIDs, with the possible exception of naproxen, also increase cardiovascular risk [25], [26]. The analyses of subgroups of patients who were treated for the short-term treatment of postoperative pain after coronary artery bypass surgery [27] or chronic heart failure [28] also demonstrated a significant increased risk of cardiovascular
Renovascular adverse effects
Sodium retention, oedema and hypertension may occur during treatments with both non-selective NSAIDs and coxibs. Meta-analyses of randomised controlled studies have shown that both NSAIDs and coxibs can increase blood pressure in both normotensive and hypertensive individuals [9]. Moreover, a destabilisation of hypertension control may occur to some extent in patients treated with both coxibs, i.e. rofecoxib or celecoxib, and naproxen [31]. Renal failure has also been reported with the use of
Strategies for appropriate NSAID use in older subjects
Aging is a key risk factor for gastrointestinal and cardiovascular complications related to NSAID use. Thus, appropriate prevention strategies should be used in the elderly and other patients at high risk. Recommendations on the use of NSAIDs and coxibs have been developed from different perspectives including rheumatology [34], gastroenterology [35] and cardiology [36]. Recently, an attempt to integrate viewpoints of different specialists and develop practical recommendations for physicians
Conclusions
The efficacy of NSAIDs for the treatment of inflammation and pain of various origins is well established. Prescribing these drugs, however, remains a challenge because a great variety of gastrointestinal and cardiovascular safety issues need to be considered, particularly in older patients. Recent recommendations suggest that prescription of non-selective NSAIDs is appropriate when the patient has average gastrointestinal risk (<70 years of age, no prior gastrointestinal events, no concomitant
Conflict of interest statement
None declared.
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