[Assessment of the number of cardio- and cerebrovascular events due to rofecoxib (Vioxx) in Germany between 2001 and 2004].
OBJECTIVE
After the recall of rofecoxib (Vioxx), there was repeated national and international discussion on the potential number of patients harmed by causally related cardio- and cerebrovascular events. In individual cases, it cannot be determined whether a myocardial infarction or stroke that occurred during rofecoxib therapy was actually directly caused by this drug. On the basis of the results of the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial and German prescription data provided by the Scientific Institute of the Local Health Care Fund, the authors therefore conservatively estimated the number of patients harmed by rofecoxib in Germany between 2001 and 2004.


METHODS
Under simplifying assumptions that, as in the VIGOR study, the risk of rofecoxib or naproxen therapy can be described by a Cox model with exponentially distributed event times, it is possible to calculate the daily risk of cardio- and cerebrovascular events in patients treated with these drugs. The estimated number of patients experiencing cardio- and cerebrovascular events under rofecoxib or naproxen therapy can be calculated by multiplying the daily risks by the defined daily doses prescribed in Germany. The difference between these numbers produces the estimated number of patients harmed by rofecoxib.


RESULTS
On the basis of the data pool, a total of 7,092 additional diseased or deceased patients due to rofecoxib therapy were estimated (95% confidence interval: 2,004-15,416). The simplifying assumptions made together with the underreporting of events in the VIGOR trial are more likely to lead to an underestimation than an overestimation of affected patients. When assessing the benefit-harm ratio of rofecoxib, it needs to be considered that its protective gastrointestinal effects were not assessed compared with the optimum long-term therapy. It can be assumed that a comparison of rofecoxib with a combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and gastric mucosal barrier protectors (e. g., misoprostol) would not have shown an advantage in favor of rofecoxib therapy.


CONCLUSIONS
The example of rofecoxib and the relatively high number of patients harmed by it in Germany indicate that, before widely prescribing a new drug, a more thorough assessment of the benefit-harm ratio of the drug is required as well as a stronger consideration of therapeutic alternatives and a timely conduct of meaningful clinical studies. The results of these studies should be promptly communicated in full to physicians and patients.
Sawicki
Peter T
PT
Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), Köln. annette.ress@iqwig.de
Bender
Ralf
R
Selke
Gisbert W
GW
Klauber
Jürgen
J
Gutschmidt
Sven
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D002544:Cerebral Infarction / Q000139:chemically induced* / Q000401:mortality; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D011307:Drug Prescriptions; D004335:Drug and Narcotic Control; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007783:Lactones / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality; D018570:Risk Assessment; D013450:Sulfones / Q000627:therapeutic use / Q000633:toxicity*
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib