Benjamin Benhuri, Hiroki Ueyama, Hisato Takagi, Alexandros Briasoulis and Toshiki Kuno* Pages 390 - 397 ( 8 )
Background: Statins are the mainstay of treatment for low-density lipoprotein cholesterol (LDL-C) lowering, however, some patients cannot tolerate statins because of adverse effects. Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are alternative treatment options. The purpose of this meta-analysis was to compare LDL-C reduction with ezetimibe vs PCSK9i in patients not on statins.
Methods: PubMed and EMBASE were searched until 14th March 2020 for randomized clinical trials (RCTs) assessing the efficacy of ezetimibe vs PCSK9i in patients not on statins. The primary outcome was a reduction in LDL-C levels. A subgroup analysis of statin intolerant patients was also performed.
Results: We identified 8 RCTs that enrolled a total of 1602 patients comparing the two pharmacotherapies. PCSK9i lowered LDL-C levels significantly more than ezetimibe (mean difference (MD): -36.5; 95% confidence interval (CI) [-38.3, -34.7, p<0.00001, I2=4%]. In the statin intolerant subgroup, PCSK9i showed significantly greater reduction in LDL-C levels compared with ezetimibe (MD: -36.1; 95% CI [-39.2, -33.1, p<0.00001, I2=21%]. There were no significant differences in LDL-C reduction between different PCSK9i dosages (140 mg once every 2 weeks vs 420 mg once every 4 weeks) (MD: -1.87; 95% CI [-4.45, 0.71, p<0.16, I2=0].
Conclusion: Among patients who are statin intolerant or not receiving statins, PCSK9i use is associated with significantly lower LDL-C levels than after treatment with ezetimibe. PCSK9i might be useful in the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) in this subset of patients.
PCSK9, ezetimibe, atherosclerosis, statin intolerance, HMG-CoA, statins.
Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003, Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Division of Cardiovascular Medicine, Section of Heart Failure and Transplantation, University of Iowa, Iowa City, IA 52242, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY 10003