title: Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas.
abstract: Nonsteroidal anti-inflammatory drugs (NSAID) have been associated with adverse cardiovascular (CV) outcomes in cancer prevention and other clinical trials. A recent meta-analysis suggested that baseline CV risk is associated with NSAID-associated adverse CV events. We evaluated the effect of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas. Trial data were analyzed to determine baseline CV risk. CV toxicity outcomes were then assessed overall and excluding high CV-risk patients. Baseline CV risk scores were evenly distributed within our overall trial population of 184 placebo (low risk, 27%; moderate risk, 34%; high risk, 39%) and 191 DFMO/sulindac (low risk, 30%; moderate risk, 29%; high risk, 41%) patients. In patients with a high baseline CV risk, the number of adverse CV events was greater among DFMO/sulindac (n = 9) than among placebo (n = 3) patients. Excluding patients with a high baseline CV risk, the numbers of adverse CV events were similar in the DFMO/sulindac (n = 7) and placebo (n = 6) arms. A high CV risk score at baseline may confer an increased risk of CV events associated with treatment with DFMO/sulindac, and a low baseline score may not increase this risk. These results have implications for future NSAID-based cancer prevention clinical trials.
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA. jzell@uci.edu
authors.forename: Jason A
authors.initials: JA
authors.lastname: Zell
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelot
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Gerner
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D012306:Risk; D013467:Sulindac / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D010919:Placebos; D013467:Sulindac; D000518:Eflornithine