HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Januzzi, J. L. Search for Related Content PubMed PubMed Citation Articles by Januzzi, J. L., Jr

Use of Biomarkers to Predict Cardiac Risk from Medications: Getting to the Heart of the Matter

Cardiac Intensive Care Unit, Massachusetts General Hospital, Boston, MA, Harvard Medical School, Boston, MA

^aAddress correspondence to the author at: Cardiology Division, Massachusetts General Hospital, 32 Fruit St., Yawkey 5984, Boston, MA, Fax 617-643-1620, E-mail JJanuzzi@partners.org

The first 20% of the full text of this article appears below.

In May 1999, the US Food and Drug Administration approved rofecoxib, the first nonsteroidal antiinflammatory drug (NSAID)¹ with specific cyclooxygenase II (COX-II) activity. Soon to follow were the approvals of other COX-II inhibitors, including celecoxib. The hypothetical advantage of COX-II inhibitors over standard NSAIDs was that COX-II inhibitors reportedly caused fewer gastrointestinal complications, thanks to their avoidance of COX-I inhibition.

Not long after the release of COX-II agents, however, concerns were voiced about the theoretical potential for cardiovascular risk associated with their use. This concern was based on the fact that although nonselective NSAIDs inhibit both COX-I and COX-II, COX-II agents had little to no inhibitory effect on COX-I, which might be accompanied by a relative prothrombotic risk due to the suppression of prostacyclin, in the absence of inhibition of thromboxane A₂. Also voiced were concerns about increased blood pressure and fluid retention—2 side effects described for COX-II inhibitors. It is interesting that less concern existed at the time about the potential cardiac risk of nonselective NSAIDs.

The prescient concerns about cardiac risk related to COX-II inhibitor use were subsequently supported by the release of clinical trial results that demonstrated significant cardiovascular risk associated with the use of these drugs (1)(2), a risk that appeared to be dose dependent and to be present even when the results were adjusted for the baseline risk of . . . [Full Text of this Article]