Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery

Abstract

In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

“…arrhythmia ͉ heart failure ͉ knockout ͉ NSAIDs ͉ fibrosis R andomized, placebo-controlled trials indicate that nonsteroidal antinflammatory drugs (NSAIDs) specific for inhibition of cyclooxygense (COX)-2 confer an increased risk of myocardial infarction and stroke (1)(2)(3)(4)(5), effects explicable by suppression of COX-2-derived products, such as prostacyclin (PGI 2 ) and prostaglandia E 2 (PGE 2 ) (6). While, the clinical spectrum of hazard is dominated by a predisposition to thrombosis, an additional feature has been congestive heart failure (1)(2)(3)(4).…”

“…While, the clinical spectrum of hazard is dominated by a predisposition to thrombosis, an additional feature has been congestive heart failure (1)(2)(3)(4). NSAIDs may variably increase blood pressure (7): studies in rodents (8,9) and a meta-analysis of clinical studies (10) suggest that this reflects inhibition of COX-2 and the specificity with which this is attained (11).…”

Cardiopulmonary bypass does not affect plasma concentration of preoperatively administered gabapentin

“…19 Adverse effects of gastropathy, impaired hemostasis, and nephrotoxicity may limit the utility of NSAIDs in the cardiac surgical population. 7,20 NSAIDs with selective COX-2 inhibition have shown promise in reducing bleeding complications postoperatively. 21 However, putative thrombotic complications have led to the withdrawal of some of these drugs from the market and, in effect, have eliminated their use in the setting of cardiac surgery.…”

“…While shown to be effective analgesics, both non-selective and COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) have potentially serious risks in this surgical group. 7,8 The alpha-2-delta ligand drugs, gabapentin and pregabalin, have been shown to reduce pain scores and opioid requirements and to improve postoperative pulmonary function in a number of surgical settings 9,10 To date, there have been no published reports on the use of these drugs in the setting of cardiac surgery.…”

A reply

“…This is recognised even by the regulatory authorities now; the USA Food and Drug Administration (FDA) concluded recently that, based upon the available data, an increased risk of cardiovascular events may be a class effect for NSAIDs [5]. It is not surprising therefore that, subsequent to the publication of the two coronary artery bypass graft (CABG) studies to which the authors of the editorial refer [6,7], the FDA have stated that the use of not only parecoxib but all NSAIDs following CABG surgery, is contra-indicated [8].…”