Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques

Abstract

Background Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography. Method Patients who had VPs (minimum FCT <65 μm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15–20 mg or atorvastatin 30–40 mg) and combination therapy group (rosuvastatin 5–10 mg or atorvastatin 10–20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U -test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis. Result Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs . intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = −9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = −9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up ( B = −0.203, t = −2.701, P = 0.010), ΔTC% ( B = −0.573, t = −2.048, P = 0.046), and Δhs-CRP % ( B = −0.30...

Associated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China

“…Fourth, it is interesting that both low and high dosages, compared with standard dosage, of statin at discharge were more likely to discontinue, which is independent of other observed predictors of statin discontinuation. Use of high-dose statin has been shown to be associated with adverse reactions 29 30. Thus, side effects, such as muscle complaints due to myopathy,31 and rhabdomyolysis,32 33 might have decreased the adherence to the statin therapy in our study.…”

Effect of ezetimibe–statin combination therapy vs. statin monotherapy on coronary atheroma phenotype and lumen stenosis in patients with coronary artery disease: a meta-analysis and trial sequential analysis

“…In total, 926 individuals (460 in the ezetimibe–statin combination therapy group and 466 in the statin monotherapy group) were included in the 11 eligible articles ( Kovarnik et al, 2012 ; Habara et al, 2014 ; Nakajima et al, 2014 ; Masuda et al, 2015 ; Tsujita et al, 2015 ; Lee et al, 2016 ; Hougaard et al, 2017 ; Hibi et al, 2018 ; Hougaard et al, 2020 ; Meng et al, 2020 ; Oh et al, 2021 ), comprising nine RCTs ( Habara et al, 2014 ; Masuda et al, 2015 ; Tsujita et al, 2015 ; Lee et al, 2016 ; Hougaard et al, 2017 ; Hibi et al, 2018 ; Hougaard et al, 2020 ; Oh et al, 2021 ), one non-randomized trial ( Nakajima et al, 2014 ), and one retrospective trial ( Meng et al, 2020 ). Eight studies involving 723 participants (358 in the dual-lipid-lowering therapy and 365 in the statin monotherapy group) reported outcomes on IVUS ( Nakajima et al, 2014 ; Masuda et al, 2015 ; Tsujita et al, 2015 ; Lee et al, 2016 ; Hougaard et al, 2017 ; Hibi et al, 2018 ; Oh et al, 2021 ), and three studies with a total of 190 participants (97 in the dual-lipid-lowering therapy and 93 in statin monotherapy group) reported outcomes on OCT ( Habara et al, 2014 ; Hougaard et al, 2020 ; Meng et al, 2020 ). All eligible studies focused on CAD, with four studies in stable angina pectoris (SAP) ( Habara et al, 2014 ; Masuda et al, 2015 ; Oh et al, 2021 ), three in acute coronary syndrome (ACS) ( Nakajima et al, 2014 ; Lee et al, 2016 ; Hibi et al, 2018 ), two in CAD ( Tsujita et al, 2015 ; Meng et al, 2020 ), and two in ST-segment elevation myocardial infarction (STEMI) ( Hougaard et al, 2017 ; Hougaard et al, 2020 ).…”

“…Eight studies involving 723 participants (358 in the dual-lipid-lowering therapy and 365 in the statin monotherapy group) reported outcomes on IVUS ( Nakajima et al, 2014 ; Masuda et al, 2015 ; Tsujita et al, 2015 ; Lee et al, 2016 ; Hougaard et al, 2017 ; Hibi et al, 2018 ; Oh et al, 2021 ), and three studies with a total of 190 participants (97 in the dual-lipid-lowering therapy and 93 in statin monotherapy group) reported outcomes on OCT ( Habara et al, 2014 ; Hougaard et al, 2020 ; Meng et al, 2020 ). All eligible studies focused on CAD, with four studies in stable angina pectoris (SAP) ( Habara et al, 2014 ; Masuda et al, 2015 ; Oh et al, 2021 ), three in acute coronary syndrome (ACS) ( Nakajima et al, 2014 ; Lee et al, 2016 ; Hibi et al, 2018 ), two in CAD ( Tsujita et al, 2015 ; Meng et al, 2020 ), and two in ST-segment elevation myocardial infarction (STEMI) ( Hougaard et al, 2017 ; Hougaard et al, 2020 ). In particular, four trials were conducted in patients without a history of statin use before enrollment ( Lee et al, 2016 ; Hougaard et al, 2017 ; Hibi et al, 2018 ; Hougaard et al, 2020 ).…”

The impact of lipid-lowering medications on coronary artery plaque characteristics

“…In another study utilizing IVUS and involving patients who underwent PCI, the use of ezetimibe in combination with background statin showed a greater reduction in LDL-C ( p < 0.001) and coronary plaque regression (78% vs. 58%; p = 0.004) than those on statin alone [55] . Statin therapy combined with ezetimibe also showed a significant increase in fibrous cap thickness compared to intensive statin monotherapy in multiple studies [ 56 , 57 ].…”