The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis

Abstract

Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3,105 participants were included in the final analysis; 1,558 (50.18%) participants received ezetimibe and statin combination therapy and 1,547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients co-administered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.

Fixed dose drug combinations – are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries

“…Besides this, there have also been FDCs containing different lipid-lowering medicines including ezetimibe combined with either simvastatin, atorvastatin, or rosuvastatin [186][187][188][189][190]. The belief is that by combining different lipid-lowering medicines with different mechanisms of action adherence can be enhanced along with improved effectiveness and outcomes [191].…”

Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges

“…The intake of statins depends on cholesterol levels and other cardiovascular risk factors that must be carefully considered and examined. Various forms of statins are commercially available and they are often prescribed in combination with other drug agents, such as ezetimibe, colesevelam, fibrates, or niacin [ 53 , 54 ], to increase their beneficial effects for the treatment of hyperlipidemia. However, statins are prescribed on a long-term basis and are well-tolerated by most people, but they can also have serious adverse effects in some cases, such as liver damage, muscle problems, neuropathy, and increased blood sugar that can lead to type 2 diabetes mellitus [ 55 ].…”

Pengaruh Komorbid dan Jenis Terapi terhadap Outcome Kolesterol Total Pasien Dislipidemia

“…16 bahwa statin efektif menurunkan atau mencapai kadar LDL < 70mg/dl pada 141 pasien, LDL 70-100 mg/dl pada 453 pasien, HDL 40-59 mg/dl sebanyak 1014 pasien, HDL ≥ 60 mg/dl pada 180 pasien dan kolesterol total <200 mg/dl pada 948 pasien 16 . Penelitian sebelumnya oleh Zhu,Y dkk (2020) 17 menyatakan statin adalah terapi pertama pada pasien dislipidemia dan penyakit atelosklerosis 17 . Statin dapat megurangi kadar kolesterol LDL sebanyak ≥ 50% dan penggunaan statin direkomendasikan jika kadar kolesterol LDL ≥ 70 mg/dL 18 .…”