Neubewertung der NSAR im dreistufigen WHO-Schmerztherapieschema

Zusammenfassung

Nichtsteroidale Antirheumatika (NSAR) sind wirksame Schmerztherapeutika. Aufgrund ihres weltweit verbreiteten Einsatzes vor allem bei älteren Patienten bleiben auch seltenere und schwere Nebenwirkungen nicht verborgen. Sie haben vielleicht deswegen den Ruf, besonders häufig mit schweren Nebenwirkungen assoziiert zu sein. Gemessen an ihrem Nutzen-Risiko-Profil schneiden NSAR im Vergleich zu kompetitiven Therapieregimen, wie sie im Dreistufenkonzept der WHO vorgesehen sind, relativ günstig ab. Die Sicherheit der NSAR-Therapie kann erhöht werden, wenn individuelle Risiken konsequent beachtet und Präventivmaßnahmen genutzt werden. Das gastrointestinale NSAR-Risiko wird durch die Komedikation mit Misoprostol oder Protonenpumpenhemmern (PPI) bzw. den Einsatz von Coxiben anstelle von tNSAR praktisch halbiert. Durch den Verzicht auf parenterale NSAR-Gaben sinkt das Apoplexrisiko. Der Verminderung des kardiovaskulären Risikos dienen an der Wirksamkeit orientierte Dosisbegrenzungen, der Einsatz kurzhalbwertzeitiger NSAR und die Beschränkung der Behandlungsdauer auf das notwendige Maß. Unterstützende nicht pharmakologische Therapieverfahren sollten genutzt werden. Bei unzureichender Wirkung ist der additive Einsatz anderer Analgetika oder das Ausweichen auf ein anderes Therapieregime sinnvoll, wenn dadurch der Nutzen erhöht wird, ohne dass das individuelle Risiko für den Patienten steigt.

Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective in treating pain. Serious and rare side effects are well known, possibly due to the widespread use of NSAIDs by older patients. However, compared to alternative therapies as suggested by WHO‘s 3-step analgesic ladder, NSAIDs have a more favourable benefit-risk profile. The safety of a NSAID therapy can be increased by taking into account the individual risk profile of a patient and applying various preventive measures. Co-medication with misoprostol or proton pump inhibitors (PPIs) and the use of coxibs instead of tNSAIDs results in a reduction of the gastrointestinal NSAID risk by approximately 50 %. Dose reduction, short duration of NSAID use and the utilisation of short half-life NSAIDs lower cardiovascular risks. Supportive, non-pharmacological therapies are recommended. In case of inadequate effects, additional analgesics or switching to another therapy need to be assessed in light of the patient‘s individual risks and benefits.

Schlüsselwörter

Schmerztherapie - WHO-Stufenschema - nichtsteroidale Antirheumatika (NSAR) - gastrointestinales Risiko - kardiovaskuläres Risiko - Coxibe

Keywords

Pain management - WHO‘s 3-step analgesic ladder - nonsteroidal anti-inflammatory drugs (NSAIDs) - gastrointestinal risk - cardiovascular risk - coxibs

• Literatur

• 1 Chutka DS, Takahashi PY, Hoel RW. Inappropriate Medications for Elderly Patients. Mayo Clin Proc 2004; 79: 122-139.
• 2 Graf JMD. Analgesic Use in the Elderly: The „Pain“ and Simple Truth: Comment on „The Comparative Safety of Analgesics in Older Adults With Arthritis“. Arch Intern Med 2010; 170: 1976-1978.
• 3 Solomon DH, Rassen JAS, Glynn RJP. et al. The Comparative Safety of Analgesics in Older Adults With Arthritis. Arch Intern Med 2010; 170: 1968-1978.
• 4 Solomon DH, Rassen JAS, Glynn RJPS. et al. The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults. Arch Intern Med 2010; 170: 1979-1986.
• 5 Jakobsson U. The epidemiology of chronic pain in a general population: results of a survey in southern Sweden. Scand J Rheumatol 2010; 39: 421-429.
• 6 WHO. Cancer Pain Relief. Geneva: 1986
• 7 Woodcock J, Witter J, Dionne RA. Stimulating the development of mechanism-based, individualized pain therapies. Nat Rev Drug Discov 2007; 6: 703-710.
• 8 Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med 1998; 105: 31S-38S.
• 9 Bombardier C, Laine L, Reicin A. et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343: 1520-1528.
• 10 Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 2006; 116: 4-15.
• 11 Bolten WW. Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases. Orthopedic Research and Reviews 2010; 2: 75-84.
• 12 Kearney PM, Baigent C, Godwin J. et al. Do selective cyclo-oxygenase-2 inhibitors and traditional nonsteroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006; 332: 1302-1308.
• 13 Grosser T, Yu Y, Fitzgerald GA. Emotion recollected in tranquility: lessons learned from the COX-2 saga. Annu Rev Med 2010; 61: 17-33.
• 14 Bresalier RS, Sandler RS, Quan H. et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092-1102.
• 15 Farkouh ME, Greenberg JD, Jeger RV. et al. Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 2007; 66: 764-770.
• 16 Grosser T. Variability in the response to cyclooxygenase inhibitors: toward the individualization of nonsteroidal anti-inflammatory drug therapy. J Investig Med 2009; 57: 709-716.
• 17 Chang CH, Shau WY, Kuo CW. et al. Increased risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study. Stroke 2010; 41: 1884-1890.
• 18 Spiegel BM, Farid M, Dulai GS. et al. Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: a meta-analysis. Am J Med 2006; 119 (448) e27-e36.
• 19 Goldstein JL, Eisen GM, Burke TA. et al. Dyspepsia tolerability from the patients ‘perspective: a comparison of celecoxib with diclofenac. Aliment Pharmacol Ther 2002; 16: 819-827.
• 20 Chan FK, Hung LC, Suen BY. et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002; 347: 2104-2110.
• 21 Silverstein FE, Graham DY, Senior JR. et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123: 241-249.
• 22 Chan FK, Hung LC, Suen BY. et al. Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 2004; 127: 1038-1043.
• 23 Chan FK, Lanas A, Scheiman J. et al. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial. Lancet 2010; 376: 173-179.
• 24 Recommendations for use of selective and nonselective nonsteroidal antiinflammatory drugs: an American College of Rheumatology white paper. Arthritis Rheum 2008; 59: 1058-1073.
• 25 Allison MC, Howatson AG, Torrance CJ. et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992; 327: 749-754.
• 26 Kuo HW, Tsai SS, Tiao MM. et al. Analgesic use and the risk for progression of chronic kidney disease. Pharmacoepidemiol Drug Saf 2010; 19: 745-751.
• 27 Vandraas KF, Spigset O, Mahic M, Slordal L. Nonsteroidal anti-inflammatory drugs: use and co-treatment with potentially interacting medications in the elderly. Eur J Clin Pharmacol 2010; 66: 823-829.
• 28 Silverstein FE, Faich G, Goldstein JL. et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. Journal of the American Medical Association 2000; 284: 1247-1255.
• 29 Schnitzer TJ, Burmester GR, Mysler E. et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 2004; 364: 665-674.
• 30 Laine L, Curtis SP, Cryer B. et al. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2007; 369: 465-473.
• 31 García Rodríguez LA, Tacconelli S, Patrignani P. Role of Dose Potency in the Prediction of Risk of Myocardial Infarction Associated With Nonsteroidal Anti-Inflammatory Drugs in the General Population. J Am Coll Cardiol 2008; 52: 1628-1636.
• 32 Catella-Lawson F, Reilly MP, Kapoor SC. et al. Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin. N Engl J Med 2001; 345: 1809-1817.
• 33 Corman SL, Fedutes BA, Ansani NT. Impact of Nonsteroidal Antiinflammatory Drugs on the Cardioprotective Effects of Aspirin. Ann Pharmacother 2005; 39: 1073-1079.