A review of the gastrointestinal safety data--a gastroenterologist's perspective.
Although NSAIDs have a well-established place for certain indications in the management of OA and RA, they are associated with significant gastrointestinal (GI) toxicity. The risk of NSAID-related upper GI events, such as dyspepsia or peptic ulcer and complications such as perforation or bleeding, is well characterized. Non-selective NSAIDs increase the risk of peptic ulcer disease approximately 5-fold, and that of upper GI bleeding 4-fold, whereas selective cyclo-oxygenase-2 (COX) inhibitors are associated with a significantly lower GI toxicity than non-selective agents. There is evidence that, while the incidence of NSAID-related upper GI complications has decreased in recent years, that of lower GI complications is increasing. Observational studies and analyses from studies, primarily designed to investigate upper GI events, suggest that lower GI complications are relatively common in NSAID users and that COX-2 selective inhibitors are associated with a lower risk of these events. Such events have been poorly characterized, but are associated with significant mortality; indeed, they may have even more serious consequences than the better characterized upper GI events. There is thus a strong case for evaluating the impact of such complications in prospective outcome studies. To facilitate such studies a new endpoint, Clinically Significant Upper or Lower GI Events, has been introduced that captures both upper and lower GI events.
Lanas
Angel
A
Servicio de Aparato Digestivo, Hospital Clínico Universitario, c/ San Juan Bosco 15, 50009 Zaragoza, Spain. alanas@unizar.es
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D010437:Peptic Ulcer / Q000139:chemically induced / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors
Epidemiology. 1997 Jan;8(1):18-24
9116088
N Engl J Med. 1992 Sep 10;327(11):749-54
1501650
Arch Intern Med. 2000 Jul 24;160(14):2093-9
10904451
J Rheumatol Suppl. 1991 Mar;28:11-4
1903808
Arthritis Rheum. 2000 Sep;43(9):1905-15
11014340
Aliment Pharmacol Ther. 2006 Sep 1;24(5):751-67
16918879
Lancet. 2007 Feb 10;369(9560):465-73
17292766
Gastrointest Endosc. 2006 Sep;64(3):445-9
16923502
Ann Intern Med. 1995 Aug 15;123(4):241-9
7611589
Gastroenterology. 1992 Sep;103(3):862-9
1499936
Clin Gastroenterol Hepatol. 2007 Jul;5(7):818-28, 828.e1-5; quiz 768
17556027
N Engl J Med. 2002 Dec 26;347(26):2104-10
12501222
Drug Healthc Patient Saf. 2009;1:47-71
21701610
Aliment Pharmacol Ther. 2007 May 15;25(10):1211-22
17451567
Ann Rheum Dis. 2004 Aug;63(8):931-9
15082468
Gastroenterology. 2008 Nov;135(5):1517-25
18823986
Clin Gastroenterol Hepatol. 2009 Nov;7(11):1177-82, 1182.e1-3
19602453
Dig Dis Sci. 1997 May;42(5):990-7
9149053
Am J Med. 2006 Mar;119(3):255-66
16490472
Clin Gastroenterol Hepatol. 2005 Feb;3(2):133-41
15704047
Curr Pharm Des. 2003;9(27):2253-66
14529405
Ann Rheum Dis. 2003 Dec;62(12):1145-55
14644851
Arch Intern Med. 2005 Oct 24;165(19):2214-20
16246985
Arthritis Rheum. 2000 Jan;43(1):4-13
10643694
J Am Geriatr Soc. 2004 May;52(5):719-24
15086651
JAMA. 2002 Jan 2;287(1):64-71
11754710
Am J Gastroenterol. 2009 Jul;104(7):1633-41
19574968
Gastroenterology. 2003 Feb;124(2):288-92
12557133
Am J Gastroenterol. 2005 Aug;100(8):1685-93
16086703
Lancet. 2002 Jan 5;359(9300):14-22
11809181
Digestion. 2006;73 Suppl 1:136-50
16498262
Am J Gastroenterol. 2008 Apr;103(4):872-82
18371130
Gastroenterology. 1997 Mar;112(3):683-9
9041228
Gut. 1987 May;28(5):527-32
3596334
Gut. 2006 Dec;55(12):1731-8
16687434
Endoscopy. 2005 Dec;37(12):1170-3
16329012
J Rheumatol. 2010 Jan;37(1):167-74
19884267
JAMA. 2000 Sep 13;284(10):1247-55
10979111
Lancet. 2007 May 12;369(9573):1621-6
17499604
Can J Gastroenterol. 2004 Oct;18(10):605-9
15497000
J Rheumatol Suppl. 1998 May;51:8-16
9596549