Michael H Davidson1, Robert S Rosenson2, Kevin C Maki2, Stephen J Nicholls2, Christie M Ballantyne2, Theodore Mazzone2, Dawn M Carlson2, Laura A Williams2, Maureen T Kelly2, Heidi S Camp2, Aditya Lele2, James C Stolzenbach2. 1. From the Department of Medicine, University of Chicago, IL (M.H.D.); Icahn School of Medicine at Mount Sinai, New York, NY (R.S.R.); Biofortis Clinical Research, Addison, IL (K.C.M.); Cardiology, University of Adelaide, Adelaide, Australia (S.J.N.); Consultant Cardiologist, Royal Adelaide Hospital, Adelaide, Australia (S.J.N.); Section of Cardiology, Section of Atherosclerosis and Vascular Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX (C.M.B.); the Maria and Alando J. Ballantyne, MD, Atherosclerosis Laboratory, and Lipid Metabolism and Atherosclerosis Clinic, The Methodist Hospital, Houston, TX (C.M.B.); Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago (T.M.); and Global Pharmaceutical Research and Development (D.M.C., L.A.W., M.T.K., H.S.C., J.C.S), and Data and Statistical Sciences (A.L.), AbbVie Inc, North Chicago, IL. mdavidsonmd@gmail.com. 2. From the Department of Medicine, University of Chicago, IL (M.H.D.); Icahn School of Medicine at Mount Sinai, New York, NY (R.S.R.); Biofortis Clinical Research, Addison, IL (K.C.M.); Cardiology, University of Adelaide, Adelaide, Australia (S.J.N.); Consultant Cardiologist, Royal Adelaide Hospital, Adelaide, Australia (S.J.N.); Section of Cardiology, Section of Atherosclerosis and Vascular Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX (C.M.B.); the Maria and Alando J. Ballantyne, MD, Atherosclerosis Laboratory, and Lipid Metabolism and Atherosclerosis Clinic, The Methodist Hospital, Houston, TX (C.M.B.); Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago (T.M.); and Global Pharmaceutical Research and Development (D.M.C., L.A.W., M.T.K., H.S.C., J.C.S), and Data and Statistical Sciences (A.L.), AbbVie Inc, North Chicago, IL.
Abstract
OBJECTIVE: To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition toAtorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. APPROACH AND RESULTS: This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ≤45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ≤100 mg/dL once and averaging ≤105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while onatorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). CONCLUSIONS: Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.
RCT Entities:
OBJECTIVE: To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of CholineFenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. APPROACH AND RESULTS: This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ≤45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ≤100 mg/dL once and averaging ≤105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). CONCLUSIONS: Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.
Authors: Peter Willeit; Lena Tschiderer; Michael J Sweeting; Simon G Thompson; Matthias W Lorenz; Elias Allara; Kathrin Reuber; Lisa Seekircher; Lu Gao; Ximing Liao; Eva Lonn; Hertzel C Gerstein; Salim Yusuf; Frank P Brouwers; Folkert W Asselbergs; Wiek van Gilst; Sigmund A Anderssen; Diederick E Grobbee; John J P Kastelein; Frank L J Visseren; George Ntaios; Apostolos I Hatzitolios; Christos Savopoulos; Pythia T Nieuwkerk; Erik Stroes; Matthew Walters; Peter Higgins; Jesse Dawson; Paolo Gresele; Giuseppe Guglielmini; Rino Migliacci; Marat Ezhov; Maya Safarova; Tatyana Balakhonova; Eiichi Sato; Mayuko Amaha; Tsukasa Nakamura; Kostas Kapellas; Lisa M Jamieson; Michael Skilton; James A Blumenthal; Alan Hinderliter; Andrew Sherwood; Patrick J Smith; Michiel A van Agtmael; Peter Reiss; Marit G A van Vonderen; Stefan Kiechl; Gerhard Klingenschmid; Matthias Sitzer; Coen D A Stehouwer; Heiko Uthoff; Zhi-Yong Zou; Ana R Cunha; Mario F Neves; Miles D Witham; Hyun-Woong Park; Moo-Sik Lee; Jang-Ho Bae; Enrique Bernal; Kristian Wachtell; Sverre E Kjeldsen; Michael H Olsen; David Preiss; Naveed Sattar; Edith Beishuizen; Menno V Huisman; Mark A Espeland; Caroline Schmidt; Stefan Agewall; Ercan Ok; Gülay Aşçi; Eric de Groot; Muriel P C Grooteman; Peter J Blankestijn; Michiel L Bots Journal: Circulation Date: 2020-06-17 Impact factor: 29.690