Review of the cardiovascular safety of COXIBs compared to NSAIDS

SUMMARY: There is no doubt that NSAIDs and COXIBS are the mainstay for managing pain and inflammation in arthritis. Overall, at therapeutically equivalent doses, both NSAIDs and COXIBs provide equivalent analgesic and anti-inflammatory efficacy. However, the gastrointestinal risk associated with NSAIDs is considerable. More recently, the cardiovascular risk associated with NSAIDs and COXIBs has become a concern. Most patients, particularly the young, can benefit from NSAIDs without the risk of serious adverse gastrointestinal or cardiovascular events. However, patients with a previous history of serious gastrointestinal complications and the elderly, who could be at risk, do require alternatives. COXIBs have significant benefits over NSAIDs in reducing the incidence of serious gastrointestinal complications (perforations, ulcers and gastric bleeding). Currently two oral COXIBs are available, celecoxib and lumiracoxib, and one parenteral COXIB, parecoxib. Celecoxib has been on the market for longer and has the largest body of evidence. The older NSAIDs, such as meloxicam, with preferential COX-2 inhibition do not have good long-term evidence of reducing the incidence of serious gastrointestinal complications. However, these agents do have evidence of tolerability, ie, reducing the less-serious gastrointestinal effects, mainly dyspepsia. The South African Rheumatoid Arthritis Association’s guidelines, amended in November 2005 recommend COXIBs for elderly patients (> 60 years) with previous gastropathy and those on warfarin and/or corticosteroids, providing they do not have contra-indications. However, caution is advised when prescribing COXIBs for patients with risk factors for heart disease. These recommendations are very similar to those made by the National Institute for Clinical Excellence (NICE). In addition, it should be noted that for those patients without any cardiovascular complications but with gastrointestinal risk factors or on aspirin, it may be necessary to add a proton pump inhibitor (PPI). PPIs, however, provide little benefit for bleeding and ulceration of the lower intestine. One consequence of this low-grade bleeding is anaemia and a general feeling of malaise in patients with rheumatic disease. Current evidence suggests that COXIBs such as rofecoxib and celecoxib do not increase small intestinal permeability and that celecoxib does not cause lower intestinal bleeding and may be of benefit to those patients with lower gastrointestinal complications. In patients at risk for cardiovascular complications, both NSAIDs and COXIBs have been shown to increase the risk of myocardial infarctions (MI), hypertension and heart failure. Studies comparing COXIBs and non-specific NSAIDs should, however, be interpreted with caution. One needs to take into account the underlying baseline cardiovascular risk of the populations being compared. COXIBs appear to be prescribed preferentially to patients who were at an increased risk of cardiovascular events compared with patients prescribed non-specific NSAIDs. When the overall risk of cardiovascular complications is relatively low and an anti-inflammatory agent is required, current evidence suggests that celecoxib is an agent of choice because of its lower cardiovascular toxicity potential compared to NSAIDs and other COXIBs.