Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease
Background: The beneficial outcomes of ezetimibe plus statin therapy are well-established in coronary artery disease, but these remain unknown in lower extremity artery disease (LEAD). Objectives: This study evaluated the efficacy of an intensified lipid-lowering strategy involving ezetimibe plus st...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | JACC: Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772963X25004995 |
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| author | Yoshihiro Iwasaki, MD, PhD Takenobu Shimada, MD, PhD Takefumi Kishimori, MD Atsuyuki Wada, MD, PhD Jumpei Koike, MD Takehiro Matsumoto, MD, PhD Takafumi Yagi, MD Masaharu Okada, MD, PhD |
| author_facet | Yoshihiro Iwasaki, MD, PhD Takenobu Shimada, MD, PhD Takefumi Kishimori, MD Atsuyuki Wada, MD, PhD Jumpei Koike, MD Takehiro Matsumoto, MD, PhD Takafumi Yagi, MD Masaharu Okada, MD, PhD |
| author_sort | Yoshihiro Iwasaki, MD, PhD |
| collection | DOAJ |
| description | Background: The beneficial outcomes of ezetimibe plus statin therapy are well-established in coronary artery disease, but these remain unknown in lower extremity artery disease (LEAD). Objectives: This study evaluated the efficacy of an intensified lipid-lowering strategy involving ezetimibe plus statins vs statin monotherapy for reducing major adverse limb events and mortality in patients with LEAD. Methods: This retrospective analysis included patients aged ≥18 years diagnosed with LEAD from the TriNetX global health care database from 2013 to 2022, excluding those with recent acute coronary syndrome or stroke. The primary outcome was the 12-month cumulative incidence of major lower limb amputation and all-cause death as a composite endpoint. Propensity score matching was used to adjust for baseline characteristics and confounders, yielding 4,204 patients in each group. Results: The composite endpoint was lower with statins plus ezetimibe vs statin monotherapy (5.8% vs 10.2%; P < 0.001; HR: 0.54; 95% CI: 0.46-0.64). Taken individually, both major lower limb amputation (2.7% vs 4.6%; P < 0.001; HR: 0.57; 95% CI: 0.45-0.72) and all-cause death (3.4% vs 6.3%; P < 0.001; HR: 0.52; 95% CI: 0.42-0.65) were significantly lower with combination therapy. Subgroup analyses showed consistent effects across all subgroups. Conclusions: Compared to statin monotherapy, an intensified lipid-lowering strategy (ie, ezetimibe plus statins), significantly reduced the incidence of major lower limb amputation and all-cause mortality in real-world patients with LEAD. |
| format | Article |
| id | doaj-art-cdd7a1fd8244409fa9bf6eae10f9122c |
| institution | Kabale University |
| issn | 2772-963X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Advances |
| spelling | doaj-art-cdd7a1fd8244409fa9bf6eae10f9122c2025-08-20T03:46:54ZengElsevierJACC: Advances2772-963X2025-09-014910207410.1016/j.jacadv.2025.102074Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery DiseaseYoshihiro Iwasaki, MD, PhD0Takenobu Shimada, MD, PhD1Takefumi Kishimori, MD2Atsuyuki Wada, MD, PhD3Jumpei Koike, MD4Takehiro Matsumoto, MD, PhD5Takafumi Yagi, MD6Masaharu Okada, MD, PhD7Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanDepartment of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, JapanDepartment of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan; Address for correspondence: Dr Takefumi Kishimori, Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase, Kusatsu, Shiga 525-8585, Japan.Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanDepartment of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanDepartment of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanDepartment of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanDepartment of Cardiovascular Medicine, Omi Medical Center, Kusatsu, JapanBackground: The beneficial outcomes of ezetimibe plus statin therapy are well-established in coronary artery disease, but these remain unknown in lower extremity artery disease (LEAD). Objectives: This study evaluated the efficacy of an intensified lipid-lowering strategy involving ezetimibe plus statins vs statin monotherapy for reducing major adverse limb events and mortality in patients with LEAD. Methods: This retrospective analysis included patients aged ≥18 years diagnosed with LEAD from the TriNetX global health care database from 2013 to 2022, excluding those with recent acute coronary syndrome or stroke. The primary outcome was the 12-month cumulative incidence of major lower limb amputation and all-cause death as a composite endpoint. Propensity score matching was used to adjust for baseline characteristics and confounders, yielding 4,204 patients in each group. Results: The composite endpoint was lower with statins plus ezetimibe vs statin monotherapy (5.8% vs 10.2%; P < 0.001; HR: 0.54; 95% CI: 0.46-0.64). Taken individually, both major lower limb amputation (2.7% vs 4.6%; P < 0.001; HR: 0.57; 95% CI: 0.45-0.72) and all-cause death (3.4% vs 6.3%; P < 0.001; HR: 0.52; 95% CI: 0.42-0.65) were significantly lower with combination therapy. Subgroup analyses showed consistent effects across all subgroups. Conclusions: Compared to statin monotherapy, an intensified lipid-lowering strategy (ie, ezetimibe plus statins), significantly reduced the incidence of major lower limb amputation and all-cause mortality in real-world patients with LEAD.http://www.sciencedirect.com/science/article/pii/S2772963X25004995all-cause mortalityezetimibeLEADmajor lower limb amputationstatin |
| spellingShingle | Yoshihiro Iwasaki, MD, PhD Takenobu Shimada, MD, PhD Takefumi Kishimori, MD Atsuyuki Wada, MD, PhD Jumpei Koike, MD Takehiro Matsumoto, MD, PhD Takafumi Yagi, MD Masaharu Okada, MD, PhD Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease JACC: Advances all-cause mortality ezetimibe LEAD major lower limb amputation statin |
| title | Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease |
| title_full | Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease |
| title_fullStr | Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease |
| title_full_unstemmed | Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease |
| title_short | Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease |
| title_sort | clinical outcomes of ezetimibe plus statins in patients with lower extremity artery disease |
| topic | all-cause mortality ezetimibe LEAD major lower limb amputation statin |
| url | http://www.sciencedirect.com/science/article/pii/S2772963X25004995 |
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