ADAPT safety results now published

A paper appearing this week in the Public Library of Science journal PLoS Clinical Trials presents findings from a large National Institutes of Health sponsored trial regarding the cardiovascular and cerebrovascular safety of two non-steroidal anti-inflammatory drugs (NSAIDs), celecoxib and naproxen. The trial was initially conducted to test whether these drugs might prevent or delay the onset of Alzheimer's disease.

The paper describes the occurrence of adverse cardiovascular events, particularly heart attacks and strokes, in some 2500 elderly people who took celecoxib, naproxen, or placebo for up to 3.5 years while participating in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). The cardiovascular risk of NSAIDs is currently a controversial and hotly debated topic. One such drug, the selective COX-2 inhibitor rofecoxib (Vioxx) has been withdrawn from the market due to concerns about its cardiovascular safety. There is also debate over the safety of other selective COX-2 inhibitors, including celecoxib. Not much data from randomized trials exists on the long-term safety of non-selective, or "traditional", NSAIDs, such as naproxen.

While ADAPT was designed to test whether celecoxib or naproxen could prevent Alzheimer's disease, the trial's treatments were terminated at the end of 2004 when concerns were emerging regarding the safety of NSAIDs. Now, the safety data from ADAPT is published in PLoS Clinical Trials.

These results do not show increased or decreased risk for cardiovascular harm among people taking celecoxib, as compared to placebo. The data do however suggest some evidence of risk among people taking naproxen, as compared to placebo. Although the ADAPT results with either drug are not definitive due to the early termination of the treatments, they are essential in contributing to the larger body of evidence on the safety of these classes of drugs.

Barbara Martin from the John Hopkins Bloomberg School of Public Health, an author of the study, comments: "Because ADAPT stands alone as a large, long-term, placebo-controlled trial of NSAIDs in the elderly, we believe the data are an important contribution to the medical literature. Particularly for safety data, 'truth' may come in small doses. We firmly believe that results from trials should be published regardless of the direction, magnitude, or statistical significance of the observed results."

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In an accompanying perspective, Steve Nissen discusses the circumstances surrounding the premature termination of treatment in ADAPT and on the difficulties surrounding interpretation of these data.

Citation: ADAPT Research Group (2006) Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). PLoS Clin Trials 1(7): e33.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT:
http://dx.doi.org/10.1371/journal.pctr.0010033

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plct-01-07-martin.pdf

CONTACT:
Barbara Martin
Johns Hopkins Bloomberg School of Public Health
Epidemiology
615 N Wolfe Street
Baltimore, MD 21205
United States of America
+1 410 614 5204
+1 410 955 0932 (fax)
bmartin@jhsph.edu

Related PLoS Clinical Trials Perspectives article:

Citation: Nissen SE (2006) ADAPT: The wrong way to stop a clinical trial. PLoS Clin Trials 1(7): e35.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pctr.0010035

PRESS-ONLY PREVIEW OF THE ARTICLE:
http://www.plos.org/press/plct-01-07-nissen.pdf

CONTACT:
Steve Nissen
Cleveland Clinic Foundation
Department of Cardiovascular Medicine
9500 Euclid Ave
Cleveland, Ohio 44195
United States of America
+1 216 445 6852
nissens@ccf.org

THE FOLLOWING ESSAY WILL ALSO BE PUBLISHED ONLINE

Citation: Ioannidis JPA (2006) Evolution and translation of research findings: From bench to where? PLoS Clin Trials 1(7): e36.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT:
http://dx.doi.org/10.1371/journal.pctr.0010036

PRESS-ONLY PREVIEW OF THE ARTICLE:
http://www.plos.org/press/plct-01-07-ioannidis.pdf

CONTACT:

John Ioannidis
University of Ioannina School of Medicine
Department of Hygiene and Epidemiology
University Campus
Ioannina, Epirus 45110
Greece
+302 651 097 807
jioannid@cc.uoi.gr

About PLoS Clinical Trials

PLoS Clinical Trials is an open access, freely available international medical journal. The journal's goal is to broaden the scope of clinical trials reporting by peer-reviewing and publishing the results of all randomized trials that are ethically and scientifically sound, irrespective of the trial's outcome. PLoS Clinical Trials aims to increase the accuracy and completeness of the evidence base for clinical decision-making. For more information see http://www.plosclinicaltrials.org.

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org


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