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Nonsteroidal Anti-Inflammatory Drugs and Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Surgery

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in perioperative pain management of patients undergoing coronary artery bypass graft surgery. However, the association of periprocedural use of NSAIDs and clinical outcomes after coronary artery bypass graft is understudied.

Methods

We conducted a retrospective analysis using pooled data from 2 multicenter randomized controlled trials (PREVENT IV [n = 3014] and MEND-CABG II [n = 3023]). Rates of death, death or myocardial infarction, and death, myocardial infarction, or stroke in the 30 days following coronary artery bypass graft surgery were compared in patients using or not using perioperative NSAIDs. Inverse probability of treatment weighting and Cox proportional hazards regression models were used to adjust for confounding.

Results

A total of 5887 patients were studied. Median age was 65 years, 78% were male, and 91% were White. NSAIDs were used in 2368 (40.2%) patients. The majority of patients (1822 [30.9%]) received NSAIDs after coronary artery bypass graft surgery; 289 (4.9%) used them prior to and after the surgery; and 257 (4.4) received NSAIDs prior to the surgery only. Adjusted 30-day outcomes were similar in patients receiving and not receiving NSAIDs (death: hazard ratio [HR] 1.18; 95% confidence interval [CI], 0.48-2.92; death or myocardial infarction: HR 0.87; 95% CI, 0.42-1.79; death, myocardial infarction, or stroke: HR 0.87; 95% CI, 0.46-1.65).

Conclusion

In this pooled data analysis, perioperative NSAID use was common among patients undergoing coronary artery bypass graft surgery and was not associated with an increased short-term risk for major adverse clinical outcomes.

Adequate pain management in patients who undergo coronary artery bypass surgery is an important goal because it increases patient comfort and ability to mobilize and participate in cardiac rehabilitation, and ultimately facilitates faster recovery. Pain following coronary artery bypass graft surgery can originate from the site of sternotomy, chest tube insertion, or peripheral vein or arterial harvest sites, or from postoperative pericarditis.1 The response to postoperative pain varies considerably among patients.2 Although acetaminophen/paracetamol is routinely prescribed after surgery, its analgesic effects are rarely sufficient for adequate pain management. Therefore, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are administered concurrently to most patients undergoing coronary artery bypass graft surgery.3 Opioids have been shown to cause postoperative nausea and vomiting, drowsiness, and respiratory depression, provoke delirium and prolonged mental confusion, and have a negative impact on early mobilization. The use of these agents is particularly a concern in older patients.4 NSAID use has been shown to increase the risk of gastrointestinal ulceration, renal dysfunction, and bleeding caused by platelet inhibition.5 Most of these NSAID-related side effects are associated with the nonselective inhibition of both COX-1 and COX-2 cyclooxygenase enzymes.6789 Many patients who undergo coronary artery bypass graft surgery receive NSAIDs prior to the procedure, but there is a paucity of data on the safety of NSAIDs in this population. Our aim was to investigate the association between NSAID use and short-term outcomes in patients undergoing coronary artery bypass graft surgery.

Methods

Study Population

We performed a retrospective analysis of data on patients enrolled in 2 large clinical trials, namely the PRoject of Ex-vivo Vein graft ENgineering via Transfection (PREVENT) IV trial—a placebo-controlled study of ex-vivo treatment of autologous vein grafts with edifoligide in 3014 patients undergoing initial coronary artery bypass graft surgery who were enrolled from 107 different sites between 2002 and 20031011—and the MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery Trial (MEND-CABG II), which studied the efficacy and safety of MC-1 (P5′-P) in reducing cardiovascular morbidity and mortality after coronary artery bypass graft. For MEND-CABG II, 3023 patients were enrolled at 130 sites in Canada, the US, and Germany between October 2006 and September 2007. Both trials were neutral and failed to show a significant improvement with the randomized therapy.1213

Clinical Outcomes

The primary outcome for this analysis was a 30-day composite of death, myocardial infarction, and stroke after hospital discharge. In PREVENT IV, the definition of myocardial infarction was an elevated day-1 postoperative creatine kinase-MB (≥5× upper limit of normal and at least 3% of the total creatine kinase) or a new >30-ms Q wave in at least 2 contiguous leads on the postoperative electrocardiogram. The secondary endpoints were 30-day death and 30-day death or nonfatal myocardial infarction. In general, adverse events were collected and coded using standard techniques.1012 Adverse events in PREVENT IV were defined as (a) renal failure (a new or worsening condition resulting in an increase in the serum creatinine to >2.0 mg/dL and >2× the patient’s baseline level or a new requirement for dialysis); (b) mediastinitis (any wound infection causing disruption of the sternum or requiring a secondary operation or stabilization of the sternum prior to discharge); and (c) bleeding or suspected bleeding requiring re-operation. Because MEND-CABG II did not prespecify adverse events, we used the reported clinical endpoint to define the adverse events.

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-Flávio de Souza Brito, MD, Rajendra H. Mehta, MD, MS, Renato D. Lopes, MD, PhD, Ralf E. Harskamp, MD, B. Daniel Lucas Jr., PharmD, Phillip J. Schulte, PhD, Jean-Claude Tardif, MD, John H. Alexander, MD, MHS

This article originally appeared in the April 2017 issue of The American Journal of Medicine.

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