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(Circulation. 2002;106:167.)
© 2002 American Heart Association, Inc.

Editorial

Cyclooxygenase-2 Inhibition and Cardiovascular Events

Bertram Pitt, MD; Carl Pepine, MD; James T. Willerson, MD

From the University of Michigan School of Medicine, Ann Arbor (B.P.); University of Florida School of Medicine, Gainesville (C.P.); and University of Texas Health Science Center, Texas Heart Institute, St Luke’s Episcopal Hospital, Houston (J.T.W.).

Correspondence to James T. Willerson, MD, SLEH/THI, 6720 Bertner Ave, Room B514 (MC 1-267), Houston, TX 77030.

Key Words: Editorials • drugs • cardiovascular disease

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The Promise

Introduction of selective cyclooxygenase (COX)-2 inhibitors held a promise of improved treatment of arthritis without the gastrointestinal effects associated with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), which effect both COX-1 and COX-2 activity. Celecoxib, etodolac, meloxicam, and rofecoxib are classified as selective COX-2 inhibitors. Initial placebo and large scale comparative trials with NSAIDs have shown the effectiveness of selective COX-2 inhibition with a lower incidence of gastrointestinal side effects in patients with arthritis.^1,2 These data, along with extensive marketing programs such as direct-to-consumer advertising, led to wide scale use.

See p 191

The Controversy

Caution to this enthusiasm was raised by suggestions that prostacyclin (PGI-2) inhibition with relatively unopposed platelet thromboxane (TX)A₂ generation may lead to thrombotic risk. Then, the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial¹ comparing rofecoxib to the NSAID naproxen in patients with rheumatoid arthritis showed a 5-fold increase in atherothrombotic cardiovascular events associated with rofecoxib. In contrast, the Celecoxib Long-Term Arthritis Safety Study (CLASS)² showed no increase in cardiovascular events with celecoxib compared with an NSAID in patients with osteoarthritis. One possible explanation for the differences between these studies may relate to findings from a direct, double-blind, randomized comparison where rofecoxib significantly raised blood pressure and increased the development of edema relative to celecoxib.³ A summary of major comparative trials with selective COX-2 inhibitors by Mukherjee et al⁴ suggested that both rofecoxib and celecoxib may be associated with an increase in cardiovascular events. Although there was no apparent evidence for increased cardiovascular events with celecoxib in CLASS,² Mukherjee . . . [Full Text of this Article]

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