Z Rheumatol 60:288 (2001)© Steinkopff Verlag 2001

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LETTER TO THE EDITORS

Dr. Wolfgang W. Bolten ())Klaus Miehlke KlinikRheumatologieLeibnizstr. 2365191 WiesbadenTel.: +49611 /5758-12Fax: +49611 /5758-88E-Mail: wbolten@t-online.de

Number Needed To KillIndividual Drug Risk with NSAIDs

It has been well established in themedical literature that non-selectivenonsteroidal anti-inflammatorydrugs (NSAIDs) can cause life-threatening gastrointestinal per-forations, ulcers and bleeding (1–3). However, it is still not very ap-parent for individual physicians ineveryday clinical practice to assessthe risk of these adverse eventsamong individual patients whoneed NSAID therapy.

The risk of death associatedwith nonselective NSAID therapyhas now been systematically quan-tified for the first time usingworldwide evidence identified fromMedLine and Embase (4). The anal-ysis included 250000 patients from15 randomized clinical trials, threecohort studies, six case-controlstudies, 12 case series and 4447case reports. It emerged that takingan NSAID for at least two monthscarries a significant risk. On aver-age, one of 1220 patients who takeNSAIDs for at least two monthswill die as a result of gastroduode-nal complications (number neededto kill). To put this into perspective,we can compare the death ratefrom NSAID gastrointestinal ad-verse events to the risks associatedwith some well-known events. Foran individual for example, takingNSAIDs for at least two months iseight times riskier than usingtransport in Germany for one year,80 to 800 times more dangerousthan a bungee jump and over 1000times more perilous than a singleflight (Fig. 1).

The study thus confirmed cur-rent national figures for Germanyof 1200 to 2400 NSAID-relateddeaths per annum (5). In addition,problems regarding the quality ofmedical care with nonselectiveNSAID use were revealed in Ger-many. For one, contrary to treat-

ment recommendations, many pa-tients on NSAID therapy are co-prescribed with H2-blockers andantacids. Apart from the addedcosts of having two medications,studies have shown that H2-block-ers and antacids are ineffective inpreventing NSAID-induced gastro-intestinal complications (6). Protonpump inhibitors and prostaglandinanalogs have been demonstrated tobe effective, but they are rarely pre-scribed. If they were given to allhigh-risk patients, the German stat-utory health insurance funds would

face additional costs of DM 1–2 bil-lion.

Studies of the number needed tokill close a gap by taking absolutedrug risks into account and thusviewing the entire picture. Burden-of-illness and NNK-approachesconfirm and complement eachother and shed light on the public-health and individual consequencesof nonselective NSAID therapy.Now more transparent decisionaids for selecting anti-inflammatorydrugs are available for all con-cerned parties, including patients.

Fig. 1 Risk of death per 1 000000. # 909 deaths per 1 462000000 passengers on scheduled 1998 trafficcarried by the airlines of 185 Contracting States [Ref. 7]. § 1.0 to 10 deaths per 1 000000 organizedbungee jumps [Ref. 8]; 15 confirmed deaths per estimated 15000000 jumps on licensed and non-li-censed facilities worldwide [Ref. 9]; 1:520000 [Ref. 10]. 6 8 739 deaths in 1997 [Ref. 11] per 81349200persons exposed [Ref. 12], i.e. not living in nursing homes, in Germany on December 31, 1996

References

1. Blower AL, Brooks A, Fenn GC et al(1997) Emergency admission forupper gastrointestinal disease andtheir relation to NSAID use. AlimentPharmacol Ther 11:283–291

2. Hernandez-Diaz S, Garcia RodriguezLA (2000) Association between non-steroidal anti-inflammatory drugsand upper gastrointestinal tractbleeding/perforation. Arch InternMed 160:2093–2099

3. Wolfe MM, Lichtenstein DR, Singh G(1999) Gastrointestinal toxicity ofnonsteroidal antiinflammatory drugs.NEJM 340:1888–1899

4. Tramèr MR, Moore RA, ReynoldsDJM, McQuay HJ (2000) Quantitativeestimation of rare adverse eventswhich follow a biological progression– a new model applied to chronicNSAID use. Pain 85:169–182

5. Bolten WW, Lang B, Wagner AV, KrobotKJ (1999) Konsequenzen und Kostender NSA-Gastropathie in Deutsch-land. Aktuelle Rheumatol 24:127–134

6. Singh G (1998) Recent considerations innonsteroidal anti-inflammatory druggastropathy. Am J Med 105:31S–38S

7. Annual Report of the Council 1998(Doc 9732). International Civil Avia-tion Organization, Montreal, Quebec,Canda.http://www.icao.int/cgi/goto.pl?icao/en/pub/rp98.htm, last visited April 14th,2000

8. UK Health and Safety Executive, Lon-don, 1991 Report

9. Personal communication UnitedStates Bungee Association, April 14th,2000

11. Codes E800–848. In: Sterbefälle nachTodesursachen in Deutschland, Ein-zelnachweis 1997, 2nd corrected edi-tion. Statistisches Bundesamt, Wies-baden (ed). Metzler-Poeschel, Stutt-gart 1999

12. Statistisches Jahrbuch für die Bun-desrepublik Deutschland. Statis-tisches Bundesamt, Wiesbaden (Ed).Metzler-Poeschel, Stuttgart 1999