BACKGROUND: Fibrates are effective antilipidemic agents with peroxisome proliferator-activated receptor agonist activity, but clinical trial data on their role in cardiovascular prevention are conflicting. We conducted a systematic review and meta-analysis of randomized clinical trials to evaluate their role in prevention of cardiovascular events. METHODS: A total of 36,489 patients from 10 published randomized placebo-controlled trials were analyzed using the Mantel-Haenszel fixed-effects model. Odds ratios were computed for cardiovascular outcomes from data pooled from the selected trials, and statistical significance was tested using the z-test statistic (2-sided alpha error <.05). RESULTS: Fibrates significantly reduced plasma total cholesterol and triglyceride levels by about 8% and 30%, respectively, and raised high-density lipoprotein cholesterol levels by about 9% compared with placebo. The odds of all-cause mortality tended to be higher (P = .08), and the odds of noncardiovascular mortality were significantly higher (P = .004) with the use of fibrates. However, these significant differences did not persist after exclusion of trials using clofibrate as the study drug. Fibrates did not significantly reduce the odds of cardiovascular mortality (P = .68), fatal myocardial infarction (MI) (P = .76), or stroke (P = .56). On the other hand, fibrates significantly reduced the odds of nonfatal MI by about 22% (P < .00001). The odds of developing cancer were not significantly higher with the use of fibrates (P = .98), nor were the odds of cancer-related death (P = .17). CONCLUSIONS: In conclusion, our meta-analysis revealed that the long-term use of fibrates significantly reduces the occurrence of nonfatal MI but has no significant effect on other adverse cardiovascular outcomes.
BACKGROUND: Fibrates are effective antilipidemic agents with peroxisome proliferator-activated receptor agonist activity, but clinical trial data on their role in cardiovascular prevention are conflicting. We conducted a systematic review and meta-analysis of randomized clinical trials to evaluate their role in prevention of cardiovascular events. METHODS: A total of 36,489 patients from 10 published randomized placebo-controlled trials were analyzed using the Mantel-Haenszel fixed-effects model. Odds ratios were computed for cardiovascular outcomes from data pooled from the selected trials, and statistical significance was tested using the z-test statistic (2-sided alpha error <.05). RESULTS: Fibrates significantly reduced plasma total cholesterol and triglyceride levels by about 8% and 30%, respectively, and raised high-density lipoprotein cholesterol levels by about 9% compared with placebo. The odds of all-cause mortality tended to be higher (P = .08), and the odds of noncardiovascular mortality were significantly higher (P = .004) with the use of fibrates. However, these significant differences did not persist after exclusion of trials using clofibrate as the study drug. Fibrates did not significantly reduce the odds of cardiovascular mortality (P = .68), fatal myocardial infarction (MI) (P = .76), or stroke (P = .56). On the other hand, fibrates significantly reduced the odds of nonfatal MI by about 22% (P < .00001). The odds of developing cancer were not significantly higher with the use of fibrates (P = .98), nor were the odds of cancer-related death (P = .17). CONCLUSIONS: In conclusion, our meta-analysis revealed that the long-term use of fibrates significantly reduces the occurrence of nonfatal MI but has no significant effect on other adverse cardiovascular outcomes.
Authors: Daniel M Rotroff; Sonja S Pijut; Skylar W Marvel; John R Jack; Tammy M Havener; Aurora Pujol; Agatha Schluter; Gregory A Graf; Henry N Ginsberg; Hetal S Shah; He Gao; Mario-Luca Morieri; Alessandro Doria; Josyf C Mychaleckyi; Howard L McLeod; John B Buse; Michael J Wagner; Alison A Motsinger-Reif Journal: Clin Pharmacol Ther Date: 2017-11-03 Impact factor: 6.875