CONTEXT: Menopausal lipid profile changes may increase cardiovascular risk. The effects of conjugated estrogens (CE)/bazedoxifene (BZA), an approved menopausal therapy, on lipids have not been fully characterized. OBJECTIVE: The purpose of this study was to determine the effects of CE/BZA on lipids in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials for ≥ 1 year. DESIGN: This was a pooled analysis of 3 randomized, double-blind, placebo (PBO)-controlled phase 3 trials (SMART-1, -4, and -5). SETTING: The study was conducted in North America, Europe, Asia-Pacific Region, and Latin America. PARTICIPANTS: Participants were nonhysterectomized postmenopausal women aged 40 to 75 years, not taking lipid-lowering medications (N = 2796). INTERVENTIONS: Treatments were CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and PBO. MAIN OUTCOME MEASURES: The adjusted mean percentage changes from baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and the LDL-C/HDL-C ratio at 12 and 24 months were measured. RESULTS: At 12 months, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg produced significant (P < .001) improvements vs PBO in TC (-4.20% and -4.37% vs -0.88%), LDL-C (-9.33% and -10.78% vs -1.08%), HDL-C (4.59% and 6.21% vs 1.30%), and the LDL-C/HDL-C ratio (-11.59% and -14.00% vs -0.84%). Triglycerides were significantly (P < .001) increased from baseline with both doses vs PBO (15.13% and 15.74% vs 4.43%). Similar trends (all P < .001) were seen at 24 months when SMART-1 and SMART-4 were pooled (TC: -3.25% and -3.13% vs 0.95%; LDL-C: -7.47% and -8.08% vs 2.95%; HDL-C: 5.91% and 7.19% vs 1.72%; triglycerides: 18.87% and 18.82% vs 6.49%; and the LDL-C/HDL-C ratio: -10.05% and -12.82% vs 2.56%). CONCLUSIONS:CE/BZA was associated with mostly favorable changes in lipid parameters for up to 2 years in nonhysterectomized postmenopausal women.
RCT Entities:
CONTEXT: Menopausal lipid profile changes may increase cardiovascular risk. The effects of conjugated estrogens (CE)/bazedoxifene (BZA), an approved menopausal therapy, on lipids have not been fully characterized. OBJECTIVE: The purpose of this study was to determine the effects of CE/BZA on lipids in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials for ≥ 1 year. DESIGN: This was a pooled analysis of 3 randomized, double-blind, placebo (PBO)-controlled phase 3 trials (SMART-1, -4, and -5). SETTING: The study was conducted in North America, Europe, Asia-Pacific Region, and Latin America. PARTICIPANTS: Participants were nonhysterectomized postmenopausal women aged 40 to 75 years, not taking lipid-lowering medications (N = 2796). INTERVENTIONS: Treatments were CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and PBO. MAIN OUTCOME MEASURES: The adjusted mean percentage changes from baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and the LDL-C/HDL-C ratio at 12 and 24 months were measured. RESULTS: At 12 months, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg produced significant (P < .001) improvements vs PBO in TC (-4.20% and -4.37% vs -0.88%), LDL-C (-9.33% and -10.78% vs -1.08%), HDL-C (4.59% and 6.21% vs 1.30%), and the LDL-C/HDL-C ratio (-11.59% and -14.00% vs -0.84%). Triglycerides were significantly (P < .001) increased from baseline with both doses vs PBO (15.13% and 15.74% vs 4.43%). Similar trends (all P < .001) were seen at 24 months when SMART-1 and SMART-4 were pooled (TC: -3.25% and -3.13% vs 0.95%; LDL-C: -7.47% and -8.08% vs 2.95%; HDL-C: 5.91% and 7.19% vs 1.72%; triglycerides: 18.87% and 18.82% vs 6.49%; and the LDL-C/HDL-C ratio: -10.05% and -12.82% vs 2.56%). CONCLUSIONS: CE/BZA was associated with mostly favorable changes in lipid parameters for up to 2 years in nonhysterectomized postmenopausal women.
Authors: Kara L Marlatt; Dragana Lovre; Robbie A Beyl; Chandra R Tate; Evelyn K Hayes; Charles F Burant; Eric Ravussin; Franck Mauvais-Jarvis Journal: Eur J Endocrinol Date: 2020-10 Impact factor: 6.664
Authors: Pathum Thilakasiri; Jennifer Huynh; Ashleigh R Poh; Chin Wee Tan; Tracy L Nero; Kelly Tran; Adam C Parslow; Shoukat Afshar-Sterle; David Baloyan; Natalie J Hannan; Michael Buchert; Andrew Mark Scott; Michael Dw Griffin; Frederic Hollande; Michael W Parker; Tracy L Putoczki; Matthias Ernst; Ashwini L Chand Journal: EMBO Mol Med Date: 2019-04 Impact factor: 12.137