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In a nutshell NSAIDs are an essential part of the therapeutic armamentarium despite their well characterised GI and CV risk profiles . Physicians should not prescribe NSAIDs before taking a careful history and doing a physical examination . When using NSAIDs , cognisance should be taken of age , comorbidities , cardiovascular risks and benefits , as well as GI risks and protection .
Finally , the appropriateness of an NSAID prescription should be emphasised , i . e ., to control inflammation and pain , rather than to control pain alone ; only then can we hope to limit the expanding NSAID epidemic .
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inhibitor therapy in acidrelated diseases - a position paper addressing benefits and potential harms of acid suppression by Carmelo Scarpignato et al , concludes that PPI therapy reduces upper GI symptoms in NSAID users . Standard dose PPIs are indicated for patients taking non-selective NSAIDs at risk for upper GI complications ( bleeding and perforation ) and for those given selective cyclooxygenase ( COX-2 ) inhibitors having had an episode of previous GI bleeding .
“ In both non-selective and COX-2 selective NSAID users , PPI therapy reduces upper GI symptoms , in particular dyspepsia . However , NSAID induced adverse events in the lower GI tract are not prevented by PPIs ,” the review states .
GI adverse effects are the most common and include a wide clinical spectrum ranging from dyspepsia , heartburn , and abdominal discomfort to more serious events such as PU with life-threatening complications , including bleeding and perforation . Since symptoms are not a reliable indicator of mucosal damage , it is important to identify factors that predict the risk of GI events in NSAID users .
“ The risk factors for upper GI bleeding ( UGIB ) associated with NSAID use has been well defined by several studies . Among them , the most important are prior history of complicated ulcer and age . Older age is common in NSAID users and those aged above 65 years carry a risk similar to those with a history of PU . Advancing age increases the risk by about 4 % per year , probably because of the presence of other associated risk factors ,” Scarpignato says .
The presence of multiple risk factors greatly increases the risk of GI complications . The role of H . pylori infection in patients taking NSAIDs and the potential benefit of eradication on upper GI risk in infected NSAID users has been controversial . However ,
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eradication of associated H . pylori infection is beneficial when starting treatment with NSAIDs or aspirin , especially in the presence of an ulcer history .
An often forgotten risk factor for upper GI complications is represented by drug combinations with NSAIDs . While the role of steroids , antiplatelet drugs , and anticoagulants is long known , the synergistic effect of selective serotonin reuptake inhibitors ( SSRIs ) has until recently been overlooked .
Over the past 15 years , several epidemiologic studies , summarised by three recent meta-analyses have shown an association between SSRI use and the occurrence of UGIB , and found that this risk is further increased among patients , who concomitantly use NSAIDs and / or hold H . pylori infection while it is lowered by concomitant PPI intake .
The most plausible mechanisms underlying this detrimental effect include a marked decrease in serotonin platelet content , with consequent impairment of platelet aggregation in response to injury and prolongation of bleeding time as well as an increase in gastric acid secretion , with potential ulcerogenic activity .
“ GI symptoms usually develop within the first few days of starting a NSAID therapy and can actually occur with the first dose of the drug . Although some studies have suggested that the first two months of treatment represent the period of greatest risk for complications with a relative risk of 4.5 %, available evidence ( from both RCTs and observational studies ) shows that the risk of GI complications is constant over time , either during short-term or long-term NSAID use ,” the study states .
“ Therefore , even a short course of NSAID therapy carries a risk of GI complications similar to that of long-term treatment . As a consequence , prevention strategies should be
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implemented regardless of the duration of therapy , especially in patients with more than one risk factor .”
PPIs effective in prevention and treatment
All RCTs have shown that PPIs are more effective than H2RAs in both preventing and treating gastroduodenal lesions . The reasons underlying the superiority of this class of antisecretory drugs have been clarified by preclinical and clinical pharmacological studies indicating that degree and duration of acid inhibition are both important factors in determining their efficacy in the prevention of NSAID injury .
“ They also reduce upper GI symptoms associated with both COX-2 selective and nonselective NSAID use . Due to the long half-life and entero-hepatic circulation of several NSAIDs , a split dose PPI might be useful ; there is , however , no evidence for the clinical usefulness of this regimen . COX-2 selective NSAIDs have an improved upper GI safety profile compared to traditional compounds , as extensively shown in endoscopy and clinical outcome studies ,” the review suggests .
The evidence is strong , with consistent reductions in events of about 50 % in large RCTs , meta-analyses of RCTs , and large observational studies in clinical practice .
“ Among patients with a prior ulcer bleed , treatment with a COX-2 inhibitor or an NSAID plus PPI is still associated with a clinically important risk of recurrent ulcer bleed ( some 10 %). In these patients , the combination of a PPI and a COX-2 inhibitor reduces the risk of upper GI bleeding compared to that of COX-2 inhibitor alone . A very recent network meta-analysis indeed found that this drug combination represents the best strategy to prevent ulcer complications ,” Scarpignato states .
References available on request . SF
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24 | May 2017 |
The Specialist Forum | Vol . 17 No . 4 |