Association of Bezafibrate Treatment With Reduced Risk of Cancer in Patients With Coronary Artery Disease.

Zaza Iakobishvili, Tal Hasin, Robert Klempfner, Nir Shlomo, Ilan Goldenberg, Ronen Brenner, Ran Kornowski, Yariv Gerber

Journal: Mayo Clinic proceedings 2020;94(7):1171-1179

PMID: 31272567

Abstract

OBJECTIVE

To evaluate the association between bezafibrate, a drug used to treat hypertriglyceridemia, and long-term cancer incidence in patients with coronary artery disease (CAD).

PATIENTS AND METHODS

The study comprised 2980 patients with CAD (mean age, 60 years; 2729 [91.6%] men) who were free of cancer and were enrolled in the Bezafibrate Infarction Prevention study, a double-blind trial conducted between May 1, 1990, and January 31, 1993, in 18 cardiology departments in Israel. Patients randomized to receive 400 mg of bezafibrate (n=1486) or placebo (n=1494) daily for a median of 6.2 years (range, 4.7-7.6 years) were followed up for incidence of cancer through the Israeli National Cancer Registry and all-cause death through the Population Registry of the State of Israel until December 31, 2013. Cox proportional hazards and Fine and Gray survival models were used to assess the bezafibrate-cancer association.

RESULTS

Clinical characteristics and laboratory values were well balanced between the 2 groups at the study entry. Over a median follow-up of 22.5 years (range, 21.2-23.9 years), cancer developed in 753 patients. With death considered a competing event, the cumulative incidence of cancer at the end of the follow-up was lower in the bezafibrate vs the placebo group (23.9%; 95 CI, 21.9%-26.1% vs 27.2%; 95 CI, 25.1%-29.4%; P=.04). The hazard ratio for cancer in the bezafibrate vs placebo groups was 0.86 (95% CI, 0.74-0.99). In mediation analysis, the association between bezafibrate treatment and cancer incidence was not sensitive to adjustment for on-trial lipid levels but was attenuated on adjustment for on-trial fibrinogen levels.

CONCLUSION

Bezafibrate treatment is associated with reduced risk of cancer among patients with CAD. Fibrinogen, but not lipid lowering, is linked to this association.

Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Address: Department of Community Cardiology, Tel Aviv District, Clalit Health Services, Tel Aviv, Israel. Electronic address: [email protected].; Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel.; Olga and Lev Leviev Heart Center, Sheba Medical Center, Tel HaShomer, Israel.; Israel Association for Cardiovascular Trials, Sheba Medical Center, Tel HaShomer, Israel.; Olga and Lev Leviev Heart Center, Sheba Medical Center, Tel HaShomer, Israel; Israel Association for Cardiovascular Trials, Sheba Medical Center, Tel HaShomer, Israel.; Department of Oncology, Edith Wolfson Medical Center, Holon, Israel.; Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel.; Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Stanley Steyer Institute for Cancer Epidemiology and Research, Tel Aviv University, Tel Aviv, Israel.
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