Abstract
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.
Keywords: PCSK9, ezetimibe, atherosclerosis, statin intolerance, HMG-CoA, statins.
Graphical Abstract
[http://dx.doi.org/10.1016/j.jacc.2019.03.009] [PMID: 30894319]
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.05.037] [PMID: 27664503]
[http://dx.doi.org/10.1007/s40256-019-00379-9] [PMID: 31724105]
[http://dx.doi.org/10.1161/JAHA.116.005367] [PMID: 28971955]
[http://dx.doi.org/10.1345/aph.1P150] [PMID: 20702755]
[http://dx.doi.org/10.1007/s11886-015-0582-z] [PMID: 25894795]
[http://dx.doi.org/10.1093/eurheartj/ehv043] [PMID: 25694464]
[http://dx.doi.org/10.1016/j.jacl.2014.03.002] [PMID: 24793444]
[http://dx.doi.org/10.1001/jamacardio.2017.0911] [PMID: 28423147]
[http://dx.doi.org/10.1016/j.jacc.2017.07.752] [PMID: 28859793]
[http://dx.doi.org/10.1002/pds.2255] [PMID: 21956915]
[http://dx.doi.org/10.1016/j.jacc.2016.12.036] [PMID: 28302290]
[http://dx.doi.org/10.1002/14651858.CD012502.pub2]
[http://dx.doi.org/10.1016/j.jacl.2020.01.001] [PMID: 32192644]
[http://dx.doi.org/10.1016/j.amjcard.2019.11.022] [PMID: 31839147]
[http://dx.doi.org/10.7326/0003-4819-151-4-200908180-00136] [PMID: 19622512]
[PMID: 31748467]
[http://dx.doi.org/10.1016/j.jacc.2014.03.018] [PMID: 24691094]
[http://dx.doi.org/10.1016/S0140-6736(12)61771-1] [PMID: 23141812]
[http://dx.doi.org/10.1016/j.jacl.2015.08.006] [PMID: 26687696]
[http://dx.doi.org/10.1001/jama.2016.3608] [PMID: 27039291]
[http://dx.doi.org/10.1016/j.ijcard.2014.06.049] [PMID: 25037695]
[http://dx.doi.org/10.1016/j.jacc.2014.03.019] [PMID: 24694531]
[http://dx.doi.org/10.1001/jama.2012.25790] [PMID: 23128163]
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.018] [PMID: 28599257]
[http://dx.doi.org/10.7326/0003-4819-158-7-201304020-00004] [PMID: 23546564]
[http://dx.doi.org/10.5551/jat.RV17030] [PMID: 30662020]
[http://dx.doi.org/10.5114/aoms.2015.49807] [PMID: 25861286]
[http://dx.doi.org/10.1007/s10557-005-5686-z] [PMID: 16453090]
[http://dx.doi.org/10.2337/dcS13-2038]
[http://dx.doi.org/10.7326/0003-4819-137-7-200210010-00015] [PMID: 12353951]
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.08.014] [PMID: 31591002]
[http://dx.doi.org/10.7326/M13-2526] [PMID: 24514899]
[http://dx.doi.org/10.1111/j.1365-2796.2008.02062.x] [PMID: 19141093]
[PMID: 12846338]
[http://dx.doi.org/10.1517/14740338.2014.932348] [PMID: 24961142]
[http://dx.doi.org/10.1007/s11789-019-00099-z] [PMID: 30838555]
[http://dx.doi.org/10.1016/j.jacc.2017.07.745] [PMID: 28886926]
[http://dx.doi.org/10.7326/M16-0838] [PMID: 28738423]
[http://dx.doi.org/10.1016/j.jacl.2019.06.008] [PMID: 31371271]
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[http://dx.doi.org/10.1016/j.jacc.2018.10.039] [PMID: 30428396]
[http://dx.doi.org/10.1002/jca.21695] [PMID: 30817043]
[http://dx.doi.org/10.1080/14656566.2016.1197202] [PMID: 27254275]
[http://dx.doi.org/10.1161/CIRCOUTCOMES.117.003939] [PMID: 29326146]
[http://dx.doi.org/10.1001/jamacardio.2019.1647] [PMID: 31166576]
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]