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

Meng, Pei-Na1; Yin, De-Lu2; Lu, Wen-Qi1; Xu, Tian1; You, Wei1; Wu, Zhi-Ming1; Wu, Xiang-Qi1; Ye, Fei1

Editor(s): Wang., Ning-Ning

Author Information
doi: 10.1097/CM9.0000000000001067
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Abstract

Introduction

Acute coronary syndromes mainly result from abrupt thrombotic occlusion based on atherosclerotic vulnerable plaques (VPs) that rupture or erode suddenly.[1–2] In general, the pathological features of VP involve the following: thin fibrous cap, large lipid core, macrophage infiltration, expansive remodeling, neovascularization, and others.[3–6] It is noteworthy that plaques with thinner fibrous cap and larger lipid necrotic core are recognized as a distinct type of VP, termed thin cap fibroatheroma (TCFA).[3–6] The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) demonstrated that TCFA was closely correlated to major adverse cardiovascular events, especially when the cap thickness was <65 μm.[4] Fibrous cap thickness (FCT) is a major determinant of plaque instability and propensity for rupture or erosion[7]; thus, increase in FCT is critical in stabilizing VPs.

Statins are known to have the ability of stabilizing plaques and inducing an increase in the FCT, especially following intensive statin treatment.[8–11] Nevertheless, high-dose statin can also cause more adverse effects, such as myalgia, increase in the levels of hepatic enzymes, and new-onset diabetes, particularly in patients from East Asian countries, such as China.[12,13] Ezetimibe is a drug that can decrease the plasma cholesterol levels by lowering cholesterol absorption from the small intestine. When used in combination with statins, it can induce a further reduction of 6% to 25% in the low-density lipoprotein (LDL-C) level, and has shown better tolerance in patients as compared to a double dose of statin.[14] Nevertheless, to our knowledge, whether the combination therapy is superior to intensive statin monotherapy in increasing the FCT of VPs has not been systemically investigated.

The present study retrospectively investigated the effect of intensive statin vs. that of low-dose statin combined with ezetimibe therapy on the progression of the FCT of VPs, as assessed using optical coherence tomography (OCT).

Methods

Ethical approval

This was a retrospective single center study that was performed with the patients’ written informed consents and approval by the local ethics committee of the Nanjing First Hospital.

Patients

Inclusion criteria

Patients (aged ≥18 years and ≤80 years) had VPs (OCT showed that the target lesion had a minimum FCT <65 μm and lipid core >90°) and deferred from intervention at our single center (Department of Cardiology, Nanjing First Hospital) from January 2014 to December 2018. They had hypercholesterolemia (LDL-C >1.8 mmol/L), and their lipid-lowering drugs only involved intensive statin (rosuvastatin 15–20 mg or atorvastatin 30–40 mg) or low-dose statin + ezetimibe (rosuvastatin 5–10 mg or atovastatin 10–20 mg + ezetimibe 10 mg) for at least a year. Moreover, patients should had undergone coronary angiography (CAG) and OCT examination at the 12-month follow-up.

Exclusion criteria

Myocardial infarction within the previous one month; left ventricular ejection fraction <40%; detection of thrombus in the target vessel on OCT examination; severe stenosis, tortuosity, and calcification at the target lesions; acute inflammation; infection; and pregnancy were the exclusion criteria.

Variables and OCT data collection

Information on clinical presentations, plasma biomarkers, as well as characteristics during CAG and OCT examination were collected using medical records and angiographic reviews.

Target VP was defined as a thin fibrous cap (minimum FCT <65 μm) and a large lipid core (>90°). For each cross section, the lumen area, lumen diameter, and FCT were evaluated at every 1-mm longitudinal interval. When there were ≥2 TCFAs, the one with the minimum FCT was considered the target VP. The FCT was measured twice, and the average value was considered for the final result.

OCT imaging was performed using a FD-OCT (ILUMIEN OPTIS OCT system, Abbott Vascular, Santa Clara, CA, USA). Images were acquired at 15 frames per second and digitally archived. The OCT images were analyzed using proprietary off-line review system (OPTISTM Metallic Stent Optimization Software-ORW Version, Abbott Vascular, CA, USA) at the core laboratory (Nanjing Cardiovascular Center, Nanjing First Hospital, Nanjing, China). At least two independent cardiologists needed to be in agreement about the results.

Statistical analyses

Categorical variables are presented as frequencies, and comparisons were performed using Fisher exact test. Student's t test was used for comparing normally distributed continuous data, and the Mann-Whitney U-test was used for comparing non-normal continuous data. The data are presented as mean ± standard deviation or median (Q1, Q3). The relationship between the ΔFCT% and other factors was investigated using linear regression analysis. First, univariate linear regression analysis was used to investigate the association of every possible risk factor [age, hypertension, diabetes, smoking, total cholesterol (TC), total triglyceride (TG), LDL-C, hypersensitive C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) at baseline and at the 12-month follow-up] and ΔFCT%. Thereafter, the variables with P value < 0.10 were used in the multivariate linear regression analysis. Computations were performed with SPSS version 18.0 (SPSS Inc., Chicago, IL, USA). A P value < 0.05 was considered statistically significant.

Results

Patient population

Total 53 patients were finally enrolled from January 2014 to December 2018 at the Department of Cardiology, Nanjing First Hospital. Based on their lipid-lowering drug treatments, they were divided into the following two groups: 26 patients were allocated to the intensive statin group (among them, 20 patients received rosuvastatin 20 mg or atorvastatin 40 mg, four reduced their rosuvastatin dose from 20 mg to 15 mg, and two lowered their atorvastatin dose from 40 mg to 30 mg after 1–3 months owing to myalgia caused by a higher dose of statin), and 27 were allocated to the combination therapy group (rosuvastatin 5–10 mg or atorvastatin 10–20 mg + ezetimibe 10 mg). As per the guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016), the maximum dose of rosuvastatin is 20 mg and that for atorvastatin is 40 to 80 mg per day in China; however, due to inexperience, atorvastatin 80 mg/day is not recommended regularly.[13] All the subjects received the above therapy for at least 1 year. OCT examinations were performed at baseline and at the 12-month follow-up.

Baseline clinical characteristics

There were no significant differences in the clinical characteristics (age, history of hypertension, diabetes mellitus, current smoking, medications, and distribution of target lesions) at baseline between the two groups (P > 0.05) [Table 1].

Table 1
Table 1:
Baseline clinical characteristics between intensive statin treatment group and low-dose statin combined with ezetimibe therapy group.

Laboratory results

There were no significant differences in the levels of aspartate aminotransferase, creatine kinase, TC, TG, LDL-C, high-density lipoprotein (HDL-C), hs-CRP, and Lp-PLA2 at baseline (P > 0.05).

The serum TC, TG, LDL-C, hs-CRP, and Lp-PLA2 levels were reduced at the 12-month follow-up in both groups. Among them, only LDL-C and Lp-PLA2 levels were significantly different between the two groups (the combination therapy group vs. intensive statin group: LDL-C, 1.36 ± 0.19 vs. 1.46 ± 0.15 mmol/L, t = 2.132, P = 0.038; Lp-PLA2, 162.00 [145.00, 175.00] vs. 187.00 [157.00, 215.00] ng/mL, t = 3.907, P < 0.001).

There were no significant differences in the ΔTG%, ΔHDL-C%, and Δhs-CRP% between the two groups (P > 0.05); however, ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group and were listed as follows (combination treatment group vs. intensive statin group: −26.17 [−27.56, −21.54]% vs. −21.44 [−23.24, −18.35]%, t = 3.548, P = 0.001; −[51.36 ± 7.05]% vs. –[45.63 ± 5.80]%, t = 3.225, P = 0.002; −33.92 [−42.02,−20.66]% vs. −30.09 [−34.81,−12.90]%, t = 2.110, P = 0.040) [Table 2].

Table 2
Table 2:
Laboratory results at baseline and 12-month follow-up between intensive statin treatment group and low-dose statin combined with ezetimibe therapy group.

OCT findings

There were no significant differences in the FCT, lipid core angle (LCA), minimum lumen diameter (MLD), and minimum lumen area (MLA) at baseline between the two groups (P > 0.05).

The FCT was increased in both the groups (the combination treatment group vs. the 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, and the ΔFCT% increased more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = −9.085, P < 0.001) [Figures 1 and 2].

Figure 1
Figure 1:
The minimum fibrous cap thickness was 50 μm at baseline in the intensive statin group (left); the minimum fibrous cap thickness was increased to 110 μm at the 12-month follow-up in the intensive statin group (right).
Figure 2
Figure 2:
The minimum fibrous cap thickness was 60 μm at baseline in the combination therapy group (left); the minimum fibrous cap thickness was increased to 140 μm at the 12-month follow-up in the combination therapy group (right).

The LCA was decreased at the 12-month follow-up in both the groups; there was no significant difference in the ΔLCA% of the two groups (P > 0.05).

MLD and MLA seemed larger at the 12-month follow-up compared to those at baseline; however, there were no significant differences between the two groups (P > 0.05) [Table 3].

Table 3
Table 3:
OCT measurements at baseline and at the 12-month follow-up between the intensive statin treatment group and the low-dose statin combined with ezetimibe therapy group.

The association of ΔFCT% and risk factors:

From the univariate linear regression analysis (including age, history of hypertension, diabetes mellitus, current smoking, TC, TG, LDL-C, hs-CRP, Lp-PLA2 at baseline, Lp-PLA2 at the 12-month follow-up, ΔTC%, ΔTG%, ΔLDL-C%, Δhs-CRP%, and ΔLp-PLA2%), serum TC (B = −18.293, t = −3.374, P = 0.001), LDL-C (B = −38.850, t = −2.759, P = 0.008), Lp-PLA2 (B = −0.136, t = 2.127, P = 0.038) at the 12-month follow-up, ΔTC% (B = −1.350, t = −3.402, P = 0.001), and Δ hs-CRP% (B = −0.179, t = −1.808, P = 0.076) were associated with the ΔFCT%.

From multivariate linear regression analysis (including TC, LDL-C, Lp-PLA2 at 12-month follow-up and ΔTC%, Δhs-CRP%), only serum Lp-PLA2 at the 12-month follow-up (B = −0.203, t = −2.701, P = 0.010) and the ΔTC% (B = −0.573, t = −2.048, P = 0.046), Δhs-CRP% (B = −0.302, t = −2.963, P = 0.005) showed an independent association with ΔFCT% [Table 4].

Table 4
Table 4:
Association of ΔFCT% and risk factors.

Discussion

The study retrospectively investigated the effect of intensive statin compared to that of low-dose statin combined with ezetimibe in VP progression as evaluated using OCT. The FCT was increased more in the low-dose statin combined with ezetimibe therapy group, and ΔFCT% was associated with the change in the serum lipid and inflammatory factor levels.

FCT is an important determinant of plaque instability[7,15]; the PROSPECT study showed that when the minimum FCT was <65 μm, it could rupture.[4] Statins have the ability to stabilize plaques and induce the regression of coronary atherosclerosis; further, they exert pleiotropic effects, such as anti-inflammation and endothelial function improvement especially in high-dose therapy.[16–19] Several studies have shown that statin therapy can increase the FCT by reducing the plasma LDL-C level.[10,20] The ΔFCT% was increased more in the intensive statin group than in the lower dose statin group.[8,10,21] The Effect of PitavaStatin on Coronary Fibrous cap Thickness-Assessment by Fourier-Domain Optical CoheRence Tomography study showed that if statins were used earlier, FCT increased more.[22] The Effect of AtorvaStatin therapY on FIbrous cap Thickness study on coronary atherosclerotic plaque, as assessed with OCT showed that statins increased the FCT and reduced the accumulation of macrophages; the advantages were more obvious in the higher dose statin treatment than in the lower dose statin treatment.[8] However, in our country, most patients are unable to tolerate high-dose statin owing to its dose-dependent adverse effects, such as myalgia and liver dysfunction.[13] Thus, there is a need for additional therapies. Ezetimibe can lower the plasma cholesterol level by reducing cholesterol absorption from the small intestine; the combination of ezetimibe and statin therapy was widely used owing to its superior effect in terms of reduction in the LDL-C and lower prevalence of adverse effects.[23] However, whether the combination therapy had a superior effect on stabilizing coronary VP, especially increasing the FCT remains unclear.[24–26] Few studies have evaluated the effect of combination therapy on the FCT of VPs. One study showed that when ezetimibe was combined with statin, it could further increase the FCT more than statin monotherapy[27]; this finding is similar to our result. However, why it is superior to intensive statin therapy? This might be attributable to a further reduction in the lipid levels and inflammatory factor levels because of combination therapy. Plasma lipid levels and inflammation are major risk factors of plaque instability[28–30]; the resolution of these two indicators is crucial for the stabilization of VP. When ezetimibe was combined with a lower dose stain, it could achieve a similar or lower reduction in the lipid percentage than intensive statin therapy, and it had good tolerance in most Chinese patients. However, whether ezetimibe monotherapy exerts an anti-inflammatory effect remains controversial.[31–35] Several studies have shown that ezetimibe monotherapy could decrease CRP, while in combination with statin, it caused additional reduction in CRP.[31–32] The Improved Reduction of Outcomes: Vytorin Efficacy International Trial study showed a further decrease in CRP when added to statins therapy.[14] However, it is unclear whether these additional benefits are related to further lipid reduction or other mechanisms of ezetimibe that accentuate these effects when combined with statins. A previous study found that ΔFCT% may be related to the reduction in TC, LDL-C, and hs-CRP,[27] comparable to our results. However, our sample size was relatively small; therefore, larger, randomized registry studies are required to confirm our findings.

This was a retrospective, observational study that employed a relatively small sample and had a selection bias of the enrolled patients. Thus, these findings strongly suggest the need for a larger, randomized registry study to validate our findings.

The present results suggest that low-dose statin combined with ezetimibe therapy could cause a profound and significant increase in the FCT as compared to intensive statin monotherapy. The decrease in the Lp-PLA2, ΔTC%, and Δhs-CRP% was independently associated with increased FCT. Thus, low-dose statin combined with ezetimibe therapy may be a better choice for stabilizing VP as compared to intensive statin therapy.

Funding

This study was supported by a grant from the Nanjing Medical Science and Technology Development Foundation, Nanjing Department of Health (No. 201803008).

Conflicts of interest

None.

References

1. Johnson TW, Räber L, di Mario C, Bourantas C, Jia H, Mattesini A, et al. Clinical use of intracoronary imaging. Part 2: acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making: an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J 2019; 40:2566–2584. doi: 10.1093/eurheartj/ehz332.
2. Ma CY, Xu ZY, Wang SP, Peng HY, Liu F, Liu JH, et al. Change of inflammatory factors in patients with acute coronary syndrome. Chin Med J 2018; 131:1444–1449. doi: 10.4103/0366-6999.233953.
3. Sugiyama T, Yamamoto E, Bryniarski K, Xing L, Lee H, Isobe M, et al. Nonculprit plaque characteristics in patients with acute coronary syndrome caused by plaque erosion vs plaque rupture: a 3-vessel optical coherence tomography study. JAMA Cardiol 2018; 3:207–214. doi: 10.1001/jamacardio.2017.5234.
4. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, et al. A prospective natural history study of coronary atherosclerosis. N Engl J Med 2011; 364:226–235. doi: 10.1056/NEJMoa1002358.
5. Arbab-Zadeh A, Fuster V. From detecting the vulnerable plaque to managing the vulnerable patient: JACC state-of-the-art review. J Am Coll Cardiol 2019; 74:1582–1593. doi: 10.1016/j.jacc.2019.07.062.
6. Obaid DR, Calvert PA, Brown A, Gopalan D, West NEJ, Rudd JHF, et al. Coronary CT angiography features of ruptured and high-risk atherosclerotic plaques: correlation with intra-vascular ultrasound. J Cardiovasc Comput Tomogr 2017; 11:455–461. doi: 10.1016/j.jcct.2017.09.001.
7. Tasar O, Kocabay G, Karabag Y, Karabay AK, Karabay CY, Kalkan S, et al. Insulin-like growth factor-1 levels predict myocardial injury and infarction after elective percutaneous coronary intervention: an optical coherence tomography study. Postepy Kardiol Interwencyjnej 2020; 16:162–169. doi: 10.5114/aic.2020.96059.
8. Komukai K, Kubo T, Kitabata H, Matsuo Y, Ozaki Y, Takarada S, et al. Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study. J Am Coll Cardiol 2014; 64:2207–2217. doi: 10.1016/j.jacc.2014.08.045.
9. Kini AS, Vengrenyuk Y, Shameer K, Maehara A, Purushothaman M, Yoshimura T, et al. Intracoronary imaging, cholesterol efflux, and transcriptomes after intensive statin treatment: the YELLOW II study. J Am Coll Cardiol 2017; 69:628–640. doi: 10.1016/j.jacc.2016.10.029.
10. Takayama T, Komatsu S, Ueda Y, Fukushima S, Hiro T, Hirayama A, et al. Comparison of the effect of rosuvastatin 2.5 mg vs 20 mg on coronary plaque determined by angioscopy and intravascular ultrasound in Japanese with stable angina pectoris (from the aggressive lipid-lowering treatment approach using intensive rosuvastatin for vulnerable coronary artery plaque [ALTAIR] randomized trial). Am J Cardiol 2016; 117:1206–1212. doi: 10.1016/j.amjcard.2016.01.013.
11. Wang Z, Cho YS, Soeda T, Minami Y, Xing L, Jia HB, et al. Three-dimensional morphological response of lipid-rich coronary plaques to statin therapy: a serial optical coherence tomography study. Coron Artery Dis 2016; 27:350–356. doi: 10.1097/MCA.0000000000000370.
12. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology /American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 64:2713–2714. doi: 10.1016/j.jacc.2014.09.017.
13. Zhu JR, Gao RL, Zhao SP, Lu GP, Zhao D, Li JJ. Joint Committee on the revision of guidelines for the prevention and treatment of dyslipidemia in Chinese adults, Guidelines for the prevention and treatment of dyslipidemia in Chinese adults (in Chinese). Chin Circul J 2016; 31:937–953. doi: 10.3969/j.issn.1000-3614.2016.10.001.
14. Bohula EA, Giugliano RP, Cannon CP, Zhou J, Murphy SA, White JA, et al. Achivement and dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132:1224–1233. doi: 10.1161/CIRCULATIONAHA.115.018381.
15. Butcovan D, Mocanu V, Baran D, Ciurescu D, Tinica G. Assessment of vulnerable and unstable carotid atherosclerotic plaques on endarterectomy specimens. Exp Ther Med 2016; 11:2028–2032. doi: 10.3892/etm.2016.3096.
16. Afolabi A, Mustafina I, Zhao L, Li L, Sun R, Hu S, et al. Does spotty calcification attenuate the response of nonculprit plaque to statin therapy?: a serial optical coherence tomography study. Catheter Cardiovasc Interv 2018; 91:582–590. doi: 10.1002/ccd.27496.
17. Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res 2017; 120:229–243. doi: 10.1161/CIRCRESAHA.116.308537.
18. Vogt K, Mahajan-Thakur S, Wolf R, Bröderdorf S, Vogel C, Böhm A, et al. Release of platelet-derived sphingosine-1-phosphate involves multidrug resistance protein 4 (MRP4/ABCC4) and is inhibited by statins. Thromb Haemost 2018; 118:132–142. doi: 10.1160/TH17-04-0291.
19. Zhang GQ, Tao YK, Bai YP, Yan ST, Zhao SP. Inhibitory effects of simvastatin on oxidized low-density lipoprotein-induced endoplasmic reticulum stress and apoptosis in vascular endothelial cells. Chin Med J 2018; 131:950–955. doi: 10.4103/0366-6999.229891.
20. Kataoka Y, Hammadah M, Puri R, Duqqal B, Uno K, Kapadia SR, et al. Plaque microstructures in patients with coronary artery disease who achieved very low low-density lipoprotein cholesterol levels. Atherosclerosis 2015; 242:490–495. doi: 10.1016/j.atherosclerosis.2015.08.005.
21. Kataoka Y, Puri R, Hammadah M, Duqqal B, Uno K, Kapadia SR, et al. Frequency-domain optical coherence tomographic analysis of plaque microstructures at nonculprit narrowings in patients receiving potent statin therapy. Am J Cardiol 2014; 114:549–554. doi: 10.1016/j.amjcard.2014.05.035.
22. Nishiquchi T, Kubo T, Tanimoto T, Ino Y, Matsuo Y, Yamano T, et al. Effect of early pitavastatin therapy on coronary fibrous cap thickness assessed by optical coherence tomography in patients with acute coronary syndrome: the ESCORT study. JACC Cardiovasc Imaging 2018; 11:829–838. doi: 10.1016/j.jcmg.2017.07.011.
23. Vavlukis M, Vavlukis A. Adding ezetimibe to statin therapy: latest evidence and clinical implications. Drugs Context 2018; 7:212534doi: 10.7573/dic.212534.
24. Ueda Y, Hiro T, Hirayama A, omatsu S, Matsuoka H, Takayama T, et al. Effect of ezetimibe on stabilization and regression of intracoronary plaque-the ZIPANGU study. Circ J 2017; 81:1611–1619. doi: 10.1253/circj.CJ-17-0193.
25. Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, et al. Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention: the multicenter randomized controlled PRECISE-IVUS trial. J Am Coll Cardiol 2015; 66:495–507. doi: 10.1016/j.jacc.2015.05.065.
26. Hibi K, Sonoda S, Kawasaki M, Otsuji Y, Murohara T, Ishii H, et al. Effects of ezetimibe-statin combination therapy on coronary atherosclerosis in acute coronary syndrome. Circ J 2018; 82:757–766. doi: 10.1253/circj.CJ-17-0598.
27. Habara M, Nasu K, Terashima M, Ko E, Yokota D, Ito T, et al. Impact on optical coherence tomographic coronary findings of fluvastatin alone versus fluvastatin + ezetimibe. Am J Cardiol 2014; 113:580–587. doi: 10.1016/j.amjcard.2013.10.038.
28. Ruotsalainen AK, Lappalainen JP, Heiskanen E, et al. Nuclear factor E2-related factor 2 deficiency impairs atherosclerotic lesion development but promotes features of plaque instability in hypercholesterolaemic mice. Cardiovasc Res 2019; 115:243–254. doi: 10.1093/cvr/cvy143.
29. Koyama K, Yoneyama K, Mitarai T, Ishibashi Y, Takahashi E, Konqoji K, et al. Association between inflammatory biomarkers and thin-cap fibroatheroma detected by optical coherence tomography in patients with coronary heart disease. Arch Med Sci 2015; 11:505–512. doi: 10.5114/aoms.2015.52352.
30. Yu ZM, Deng XT, Qi RM, Xiao LY, Yang CQ, Gong T. Mechanism of chronic stress-induced reduced atherosclerotic medial area and increased plaque instability in rabbit models of chronic stress. Chin Med J 2018; 131:161–170. doi: 10.4103/0366-6999.222322.
31. Catapano AL, Pirillo A, Norata GD. Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials. Br J Pharmacol 2017; 174:3973–3985. doi: 10.1111/bph.13805.
32. Lin H, Zhang YM. The effect of ezetimibe and simvastatin combination therapy on percutaneous coronary intervention patients. Int J Cardiol 2017; 242:1–3. doi: 10.1016/j.ijcard.2016.10.083.
33. Tie C, Gao K, Zhang N, Zhang SZ, Shen JL, Xie XJ, et al. Ezetimibe attenuates atherosclerosis associated with lipid reduction and inflammation inhibition. PLoS One 2015; 10:e0142430doi: 10.1371/journal.pone.0142430.
34. Jackowska P, Chałubiński M, Łuczak E, Wojdan K, Gorzelak-Pabis P, Olszewska-Banaszczyk M, et al. The influence of statin monotherapy and statin-ezetimibe combined therapy on FoxP3 and IL 10 mRNA expression in patients with coronary artery disease. Adv Clin Exp Med 2019; 28:1243–1248. doi: 10.17219/acem/108627.
35. Wu NQ, Guo YL, Zhu CG, Gao Y, Zhao X, Sun D, et al. Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers. Lipids Health Dis 2018; 17:265doi: 10.1186/s12944-018-0909-z.
Keywords:

Statins; Ezetimibe; Fibrous cap thickness; Coronary vulnerable plaques; Optical coherence tomography

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