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J Thorac Cardiovasc Surg 2003;126:420-427
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study

^a Washington Hospital Center, Washington, DC, USA
^c Med. Universitätsklinik Herzchirurgische Klinik, Luebeck, Germany
^c University of Louisville, Louisville, Ky, USA
^d St Louis University Medical Center, St Louis, Mo, USA
^e University of Hawaii, Honolulu, Hawaii, USA
^f Aventis Pharmaceuticals, Inc., Bridgewater, NJ, USA
^g Lindner Center/Ohio Heart Health Center, Cincinnati, Ohio, USA
^h Flinders Private Hospital, Bedford Park, Australia
ⁱ Universitetssjukhuset, Lund, Sweden
^j Institue de Cardiologie de Montreal, Montreal, Quebec, Canada

Received for publication June 4, 2002; revisions received October 10, 2002; revisions received October 23, 2002; accepted for publication December 2, 2002.

^* Address for reprints: Steven W. Boyce, MD, Washington Hospital Center, 106 Irving Street NW, Suite 316, South Tower, Washington, DC 20010, USA
steven.w.boyce{at}medstar.net

OBJECTIVES: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery.

METHODS: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients 18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and 2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint.

RESULTS: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P = .027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P = .005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P = .033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population.

CONCLUSIONS: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.

Key Words: 16 • 23 • 31

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