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Comparison of non-steroidal anti-inflammatory drugs

  • a - Bhala N, Emberson J, Merhi A et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analysis of individual participant data from randomized trials. Lancet 2013 (August 31); 382: 769-79 [Link]
  • Compiled by: Peter Ritzmann
  • Commented by: Peter Ritzmann
  • infomed screen volume 17 (2013), number 5
    Date of issue: October 2013
Since the withdrawal of rofecoxib (Vioxx®) 9 years ago, more attention has been paid to the cardiovascular risk of non-steroidal anti-inflammatory drugs (NSAIDs). Several meta-analyzes of studies subsequently showed that not only COX-2-selective NSAIDs (the so-called coxibs) but also traditional NSAIDs increase the risk of cardiovascular, especially coronary events. A network analysis by a Bern study group that summarized 31 randomized studies with NSAIDs, for example, came to the conclusion that cardiovascular events tended to be more frequent among all NSAIDs examined than with placebo and that naproxen (Proxen®, etc.) had the lowest cardiovascular risks among them seems.1 The current meta-analysis of the "Coxib and traditional NSAID Trialists' (CNT) Collaboration" now considered 280 randomized studies in which NSAIDs were compared with placebo or with each other. Those responsible for the study tried to access the individual data of the participants, which at least succeeded in most studies with coxibs or high-dose traditional NSAIDs.
For the coxibs as a group, the results of the meta-analyzes show an increase in the risk of a severe cardiovascular event compared to placebo of about a third (relative risk of 1.37), mainly due to an increase in the risk of severe coronary events by about three Quarter (RR 1.76). The results for high-dose diclofenac (Voltaren® and others; 75 mg twice a day; RR of 1.41 and 1.70) are comparable with this. The results for high-dose ibuprofen (Brufen® et al .; 3 times 800 mg daily), in which only the coronary events but not the overall cardiovascular events were statistically significantly more frequent, are somewhat more uncertain, because they are based on fewer events. In contrast, there was no increased risk of severe cardiovascular events for high-dose naproxen (500 mg twice daily; RR 0.93). The risk of heart failure and complications in the upper gastrointestinal tract was significantly higher for all NSAIDs examined than for placebo. For the latter, the situation was opposite to that for the cardiovascular events: the risk appeared to be the most increased under naproxen (RR 4.22), followed by ibuprofen (RR 3.97), diclofenac (RR 1.89) and the coxibs (RR 1 , 81).
This large review article, which for the meta-analyzes was largely based on the individual data of the examined persons, confirms earlier studies that confirmed that naproxen had a lower cardiovascular risk than other NSAIDs. The most obvious explanation for this is that the more pronounced COX-1 inhibition of naproxen can compensate for negative cardiovascular effects of COX-2 inhibition via platelet inhibition. The fact that 20% of the subjects also took ASA to inhibit platelets apparently could not compensate for this difference. In the current analysis, diclofenac appears to be closer to the coxibs than to the traditional NSAIDs in terms of the spectrum of side effects, ibuprofen takes a kind of intermediate position. Despite all the caution with which the results of such a meta-analysis must be interpreted, naproxen appears to be the NSAID of choice today when used in high doses and with an increased cardiovascular risk. The gastrointestinal risk, which seems to be particularly high with naproxen, should not be neglected, but is comparatively easy to influence in the case of a higher risk or long-term use (e.g. with the simultaneous administration of a gastric acid blocker).
Summarized and commented by Peter Ritzmann
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Non-Steroidal Anti-Inflammatory Drugs Compared (October 2013)