Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes

A meta-analysis

Namki Hong, Yong Ho Lee, Kenichi Tsujita, Jorge A. Gonzalez, Christopher M. Kramer, Tomas Kovarnik, George N. Kouvelos, Hiromichi Suzuki, Kyungdo Han, Chan Joo Lee, Sungha Park, byungwan lee, Bong Soo Cha, Eun Seok Kang

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Abstract

Background: Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes. Methods: Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression. Results: A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I2=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; Pheterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038). Conclusion: Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalEndocrinology and Metabolism
Volume33
Issue number2
DOIs
Publication statusPublished - 2018 Jun 1

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Meta-Analysis
Therapeutics
Ezetimibe
Sample Size
LDL Cholesterol
Randomized Controlled Trials
Placebos
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Hong, Namki ; Lee, Yong Ho ; Tsujita, Kenichi ; Gonzalez, Jorge A. ; Kramer, Christopher M. ; Kovarnik, Tomas ; Kouvelos, George N. ; Suzuki, Hiromichi ; Han, Kyungdo ; Lee, Chan Joo ; Park, Sungha ; lee, byungwan ; Cha, Bong Soo ; Kang, Eun Seok. / Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes : A meta-analysis. In: Endocrinology and Metabolism. 2018 ; Vol. 33, No. 2. pp. 219-227.
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title = "Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes: A meta-analysis",
abstract = "Background: Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes. Methods: Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression. Results: A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1{\%} men; 7,298 with diabetes [25.9{\%}]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I2=14.7{\%}, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; Pheterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038). Conclusion: Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.",
author = "Namki Hong and Lee, {Yong Ho} and Kenichi Tsujita and Gonzalez, {Jorge A.} and Kramer, {Christopher M.} and Tomas Kovarnik and Kouvelos, {George N.} and Hiromichi Suzuki and Kyungdo Han and Lee, {Chan Joo} and Sungha Park and byungwan lee and Cha, {Bong Soo} and Kang, {Eun Seok}",
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Hong, N, Lee, YH, Tsujita, K, Gonzalez, JA, Kramer, CM, Kovarnik, T, Kouvelos, GN, Suzuki, H, Han, K, Lee, CJ, Park, S, lee, B, Cha, BS & Kang, ES 2018, 'Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes: A meta-analysis', Endocrinology and Metabolism, vol. 33, no. 2, pp. 219-227. https://doi.org/10.3803/EnM.2018.33.2.219

Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes : A meta-analysis. / Hong, Namki; Lee, Yong Ho; Tsujita, Kenichi; Gonzalez, Jorge A.; Kramer, Christopher M.; Kovarnik, Tomas; Kouvelos, George N.; Suzuki, Hiromichi; Han, Kyungdo; Lee, Chan Joo; Park, Sungha; lee, byungwan; Cha, Bong Soo; Kang, Eun Seok.

In: Endocrinology and Metabolism, Vol. 33, No. 2, 01.06.2018, p. 219-227.

Research output: Contribution to journalArticle

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T1 - Comparison of the effects of ezetimibe-statin combination therapy on major adverse cardiovascular events in patients with and without diabetes

T2 - A meta-analysis

AU - Hong, Namki

AU - Lee, Yong Ho

AU - Tsujita, Kenichi

AU - Gonzalez, Jorge A.

AU - Kramer, Christopher M.

AU - Kovarnik, Tomas

AU - Kouvelos, George N.

AU - Suzuki, Hiromichi

AU - Han, Kyungdo

AU - Lee, Chan Joo

AU - Park, Sungha

AU - lee, byungwan

AU - Cha, Bong Soo

AU - Kang, Eun Seok

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes. Methods: Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression. Results: A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I2=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; Pheterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038). Conclusion: Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

AB - Background: Ezetimibe-statin combination therapy has been found to reduce low density lipoprotein cholesterol levels and the risk of major adverse cardiovascular events (MACEs) in large trials. We sought to examine the differential effect of ezetimibe on MACEs when added to statins according to the presence of diabetes. Methods: Randomized clinical trials with a sample size of at least 50 participants and at least 24 weeks of follow-up that compared ezetimibe-statin combination therapy with a statin- or placebo-controlled arm and reported at least one MACE, stratified by diabetes status, were included in the meta-analysis and meta-regression. Results: A total of seven trials with 28,191 enrolled patients (mean age, 63.6 years; 75.1% men; 7,298 with diabetes [25.9%]; mean follow-up, 5 years) were analysed. MACEs stratified by diabetes were obtained from the published data (two trials) or through direct contact (five trials). No significant heterogeneity was observed among studies (I2=14.7%, P=0.293). Ezetimibe was associated with a greater reduction of MACE risk in subjects with diabetes than in those without diabetes (pooled relative risk, 0.84 vs. 0.93; Pheterogeneity=0.012). In the meta-regression analysis, the presence of diabetes was associated with a greater reduction of MACE risk when ezetimibe was added to statins (β=0.87, P=0.038). Conclusion: Ezetimibe-statin combination therapy was associated with greater cardiovascular benefits in patients with diabetes than in those without diabetes. Our findings suggest that ezetimibe-statin combination therapy might be a useful strategy in patients with diabetes at a residual risk of MACEs.

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