Zusammenfassung
Im Zuge der Diskussion über die kardiovaskuläre Sicherheit der einst medienwirksam als neuer Meilenstein der Schmerztherapie angepriesenen selektiven COX-2 Inhibitoren, die mit den Marktrücknahmen der Präparate Vioxx (Rofecoxib) 2004 und Bextra (Valdecoxib) 2005 gipfelte, geraten nun auch die klassischen NSAR in den Blickpunkt. Wie sicher sind die "altbewährten" NSAR wirklich bezüglich kardiovaskulärer Ereignisse? Langzeitstudien belegen ein mit den COX-2 Hemmern vergleichbares Gesamtrisiko. In der perioperativen Kurzzeitanwendung haben dennoch beide Substanzklassen noch ihren Stellenwert. Sie sollten jedoch auch hier nur nach gründlicher Risikoabwägung und keinesfalls routinemäßig eingesetzt werden.
Abstract
Concerning the current discussion about cardiovascular toxicity of the selective COX-2 inhibitors, recently advertised in the media as a new milestone in the management of pain, culminating in the market withdrawal of the preparations Vioxx (rofecoxib) in 2004 and Bextra (valdecoxib) in 2005, the classical NSAIDs are now spotlighted. How safe are the "well established" NSAIDs regarding adverse cardiovascular events?
Long term studies now show a similar overall risk compared to the selective COX-2 inhibitors. The short lasting perioperative administration of both drug classes are still indicated. However, even here they should be only used after a systematic risk-calculation and not on a routine basis.
Schlüsselwörter:
NSAR - COXibe - Kardiovaskuläre Ereignisse
Key words:
NSAIDs - Coxibs - Cardiovascular events
Literatur:
-
1
Bolten WW, Lang B, Wagner AV, Krobot KJ.
Konsequenzen und Kosten der NSAR-Gastropathie in Deutschland.
Akt Rhematol.
1999;
24
127-1342
-
2
Elia N, Lysakowski C, Tramèr MR.
Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials.
Anesthesiology.
2005;
103
1296-1304
-
3
Bresalier R., Sandler R, Quan H, Bolognese J, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam M, Baron J.
Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial investigators.
New Engl. J. Med.
2005;
352
1092-1102
-
4
Bresalier R., Sandler R, Quan H. et al. .
Adenomatous Polyp Prevention on Vioxx (APPROVE) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial (published correction appears in New Eng.
J. Med.
2005;
352
1092-1102
-
5
Bombardier C, Laine L, Reicin A. et al. .
Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.
N Engl J Med.
2000;
343
1520-8
-
6
Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M..
Risk of cardiovascular events and rofecoxib: cumulative meta-analysis.
Lancet.
2004;
364
2021-2029
-
7
Solomon SD, McMurray JJV, Pfeffer MA. et al. .
Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.
N Engl J Med.
2005;
80
-
8
Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R..
Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis.
J R Soc Med.
2006;
99
132-140
-
9
Ott E., Nussmeier N, Duke P, Feneck R, Alston R, Snabes M, Hubbard R, Hsu P, Saidman L, Mangano D..
Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J. Thorac.
Cardiovasc. Surg.
2003;
125
1481-1492
-
10
Nussmeier N, Whelton A, Brown M, Langford R, Hoef A, Parlow J, Boyce S, KM V..
Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.
NewEngl. J. Med.
2005;
352
1081-1091
-
11
Hippisley-Cox J, Coupland C..
Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional nonsteroidal anti-inflammatory drugs: population based nested case control analysis.
Brit. Med. J.
2005;
330
1366-1372
-
12
Johnsen SP, Larsson H, Tarone RE, McLaughlin JK, Norgard B, Soren F, Sorensen HT..
Risk of hospitalization for myocardial infarction among users of Rofecoxib, Celecoxib, and Other NSAIDs.
Arch. Int. Med.
2005;
165
978-984
-
13
Singh G, Mithal A, Triadafilopoulos G..
Both selective and non selective cox-2 inhibitors and non selective NSAIDs increase the risk of acute myocardial infarction in patients with arthritis: selectivity is with the patient, not the drug class.
Annals Rheum Dis.
2005;
64
-
14
Fischer LM, Schlienger RG, Matter CM. et al. .
Current use of non-steroidal anti-inflammatory drugs and the risk of acute myocardial infarction.
Pharmacotherapy.
2005;
25
503-10
-
15
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
1633-44
-
16
Hernandez-Diaz S, Varas-Lorenzo C, Garcia LA. Rodriguez.
Non-steroidal anti-inflammatory drugs and the risk of acute myocardial infarction.
Basic Clin Pharmacol Toxicol.
2006;
98
266-74
-
17
Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C..
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-infl ammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.
BMJ.
2006;
152
237-45
-
18
Cannon CP, Curtis SP, Bolognese JA, Laine L..
Clinical trial design and patient demographics of the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study program cardiovascular outcomes with etoricoxib vs. diclofenac in patients with osteoarthritis and rheumatoid arthritis.
Am Heart J.
2006;
152
-
19
Brock TG, McNish RW, Peters-Golden M..
Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2.
J Biol Chem.
1999;
274
11660-6
-
20
Rabausch K, Bretschneider E, Sarbia M. et al. .
Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins.
Circ Res.
2005;
96
-
21
Cheng HF, Harris RC..
Renal effects of nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2-inhibitors.
Curr Pharm Des.
2005;
11
1795-1804
PD Dr. med. Leopold Eberhart
Email: eberhart@staff.uni-marburg.de
Dr. med. Henning Lange
Email: Henning.Lange@med.uni-marburg.de
