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.
OBJECTIVE
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 > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =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.
Boyce
Steven W
SW
Washington Hospital Center, 106 Irving Street NW, Suite 316, South Tower, Washington, DC 20010, USA. steven.w.boyce@medstar.net
Bartels
Claus
C
Bolli
Roberto
R
Chaitman
Bernard
B
Chen
John C
JC
Chi
Eric
E
Jessel
Andreas
A
Kereiakes
Dean
D
Knight
John
J
Thulin
Lars
L
Theroux
Pierre
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002423:Cause of Death; D015331:Cohort Studies; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D052279:Creatine Kinase, MB Form; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006146:Guanidines / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality* / Q000628:therapy*; D009656:North America / Q000453:epidemiology; D011183:Postoperative Complications / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012720:Severity of Illness Index; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D007527:Isoenzymes; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form