Nichtsteroidale Antirheumatika (NSAR) – an der Schnittstelle gastrointestinaler Nebenwirkungen und kardiovaskulärer Risiken

Zusammenfassung

Nicht-steroidale Antirheumatika (NSAR) gehören aufgrund ihrer anti-inflammatorischen, analgetischen und antipyretischen Eigenschaften nicht nur im Fachbereich der Rheumatologie zu den am häufigsten verordneten Substanzen. Bei der Ko-Medikation von NSAR sind sowohl gastrointestinale Nebenwirkungen als auch zerebro- und kardiovaskuläre Komplikationen zu berücksichtigen und das individuelle Risiko des einzelnen Patienten vor Beginn einer Therapie genau definieren.

Summary

Because of their anti-inflammatory, analgesic and antipyretic properties non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed throughout all medical fields. Both gastrointestinal as well as cerebro- and cardiovascular risk needs to be considered. Especially before starting a long-term medical treatment with NSAIDs the individual gastrointestinal and cardiovascular risk of the patient has to be assessed carefully.

Schlüsselwörter

NSAR - kardiovaskuläres Risiko - gastrointestinale Blutung

Keywords

NSAIDs - cardiovascular risk - gastrointestinal bleeding

Literatur

• 1 Abraham N S, El-Serag H B, Hartman C, Richardson P, Deswal A. Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident.  Aliment Pharmacol Ther. 2007;  25 913-924
• 2 av-Citrin O, Arnon J, Shechtman S, Schaefer C, van Tonningen M R, Clementi M, SM, Robert-Gnansia E, Valti E, Malm H, Ornoy A. The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study.  Aliment Pharmacol Ther. 2005;  21 269-275
• 3 Bidaut-Russell M, Gabriel S E. Adverse gastrointestinal effects of NSAIDs: consequences and costs.  Best Pract Res Clin Gastroenterol. 2001;  15 739-753
• 4 Bresalier R S, Sandler R S, Quan H, Bolognese J A, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam M A, Baron J A. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.  N Engl J Med. 2005;  352 1092-1102
• 5 Catella-Lawson F, Reilly M P, Kapoor S C, Cucchiara A J, DeMarco S, Tournier B, Vyas S N, FitzGerald G A. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin.  N Engl J Med. 2001;  345 1809-1817
• 6 Chan F K, Abraham N S, Scheiman J M, Laine L. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents.  Am J Gastroenterol. 2008;  103 2908-2918
• 7 Chan F K, Chung S C, Suen B Y, Lee Y T, Leung W K, Leung V K, Wu J C, Lau J Y, Hui Y, Lai M S, Chan H L, Sung J J. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen.  N Engl J Med. 2001;  344 967-973
• 8 Chan F K, Wong V W, Suen B Y, Wu J C, Ching J Y, Hung L C, Hui A J, Leung V K, Lee V W, Lai L H, Wong G L, Chow D K, To K F, Leung W K, Chiu P W, Lee Y T, Lau J Y, Chan H L, Ng E K, Sung J J. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.  Lancet. 2007;  369 1621-1626
• 9 Dalton S O, Johansen C, Mellemkjaer L, Norgard B, Sorensen H T, Olsen J H. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study.  Arch Intern Med. 2003;  163 59-64
• 10 Gabriel S E, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis.  Ann Intern Med. 1991;  115 787-796
• 11 Gilard M, Arnaud B, Cornily J C, Le G G, Lacut K, Le C G, Mansourati J, Mottier D, Abgrall J F, Boschat J. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study.  J Am Coll Cardiol. 2008;  51 256-260
• 12 Goldstein J L, Eisen G M, Lewis B, Gralnek I M, Zlotnick S, Fort J G. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo.  Clin Gastroenterol Hepatol. 2005;  3 133-141
• 13 Graham D Y, Chan F K. NSAIDs, risks, and gastroprotective strategies: current status and future.  Gastroenterology. 2008;  134 1240-1246
• 14 Graham D Y, Opekun A R, Willingham F F, Qureshi W A. Visible small-intestinal mucosal injury in chronic NSAID users.  Clin Gastroenterol Hepatol. 2005;  3 55-59
• 15 Hallas J, Dall M, Andries A, Andersen B S, Aalykke C, Hansen J M, Andersen M, Lassen A T. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study.  BMJ. 2006;  333 726
• 16 Hawkey C J, Ell C, Simon B, Albert J, Keuchel M, McAlindon M, Fortun P, Schumann S, Bolten W, Shonde A, Hugot J L, Yu V, Arulmani U, Krammer G, Rebuli R, Toth E. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole.  Clin Gastroenterol Hepatol. 2008;  6 536-544
• 17 Ho P M, Maddox T M, Wang L, Fihn S D, Jesse R L, Peterson E D, Rumsfeld J S. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome.  JAMA. 2009;  301 937-944
• 18 Huang J Q, Sridhar S, Hunt R H. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.  Lancet. 2002;  359 14-22
• 19 Kearney P M, Baigent C, Godwin J, Halls H, Emberson J R, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.  BMJ. 2006;  332 1302-1308
• 20 Laine L, Curtis S P, Langman M, Jensen D M, Cryer B, Kaur A, Cannon C P. Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory drug diclofenac.  Gastroenterology. 2008;  135 1517-1525
• 21 Lanas A, Garcia-Rodriguez L A, Arroyo M T, Gomollon F, Feu F, Gonzalez-Perez A, Zapata E, Bastida G, Rodrigo L, Santolaria S, Guell M, de Argila C M, Quintero E, Borda F, Pique J M. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations.  Gut. 2006;  55 1731-1738
• 22 Lanas A, Perez-Aisa M A, Feu F, Ponce J, Saperas E, Santolaria S, Rodrigo L, Balanzo J, Bajador E, Almela P, Navarro J M, Carballo F, Castro M, Quintero E. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use.  Am J Gastroenterol. 2005;  100 1685-1693
• 23 Loke Y K, Trivedi A N, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs.  Aliment Pharmacol Ther. 2008;  27 31-40
• 24 Malfertheiner P, Bellutti M. Ulkuskranheit. Klinische Bewertung 2006.  Internist (Berl). 2006;  47 588-595
• 25 Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers E J. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report.  Gut. 2007;  56 772-781
• 26 McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2.  JAMA. 2006;  296 1633-1644
• 27 Patrono C, Garcia Rodriguez L A, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis.  N Engl J Med. 2005;  353 2373-2383
• 28 Pilotto A MF, Franceschi M, Leandro G, Battaglia G, Germana B, Marin R, Valerio G. Pantoprazole versus one-week Helicobacter pylori eradication therapy for the prevention of acute NSAID-related gastroduodenal damage in elderly subjects.  Aliment Pharmacol Ther. 2000;  14 1077-1082
• 29 Sachs G, Shin J M, Howden C W. Review article: the clinical pharmacology of proton pump inhibitors.  Aliment Pharmacol Ther. 2006;  23 Suppl 2 2-8
• 30 Scheiman J M, Yeomans N D, Talley N J, Vakil N, Chan F K, Tulassay Z, Rainoldi J L, Szczepanski L, Ung K A, Kleczkowski D, Ahlbom H, Naesdal J, Hawkey C. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.  Am J Gastroenterol. 2006;  101 701-710
• 31 Schnitzer T J, Burmester G R, Mysler E, Hochberg M C, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Matchaba P, Gimona A, Hawkey C J. 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
• 32 Siller-Matula J M, Spiel A O, Lang I M, Kreiner G, Christ G, Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel.  Am Heart J. 2009;  157 148-5
• 33 Solomon S D, McMurray J J, Pfeffer M A, Wittes J, Fowler R, Finn P, Anderson W F, Zauber A, Hawk E, Bertagnolli M. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.  N Engl J Med. 2005;  352 1071-1080
• 34 Sorensen H T, Mellemkjaer L, Blot W J, Nielsen G L, Steffensen F H, McLaughlin J K, Olsen J H. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin.  Am J Gastroenterol. 2000;  95 2218-2224
• 35 Tolia V, Boyer K. Long-term proton pump inhibitor use in children: a retrospective review of safety.  Dig Dis Sci. 2008;  53 385-393
• 36 Vergara M, Catalan M, Gisbert J P, Calvet X. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users.  Aliment Pharmacol Ther. 2005;  21 1411-1418
• 37 Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture.  Calcif Tissue Int. 2006;  79 76-83
• 38 Vonkeman H E, Klok R M, Postma M J, Brouwers J R, van de Laar M A. Direct medical costs of serious gastrointestinal ulcers among users of NSAIDs.  Drugs Aging. 2007;  24 681-690
• 39 Yang Y X, Lewis J D, Epstein S, Metz D C. Long-term proton pump inhibitor therapy and risk of hip fracture.  JAMA. 2006;  296 2947-2953