Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention

Tsujita, Kenichi; Sugiyama, Seigo; Sumida, Hitoshi; Shimomura, Hideki; Yamashita, Takuro; Yamanaga, Kenshi; Komura, Naohiro; Sakamoto, Kenji; Oka, Hideki; Nakao, Kōichi; Nakamura, Sunao; Ishihara, Masaharu; Matsui, Kunihiko; Sakaino, Naritsugu; Nakamura, Natsuki; Yamamoto, Nobuyasu; Koide, Shunichi; Matsumura, Toshiyuki; Fujimoto, Kazuteru; Tsunoda, Ryusuke; Morikami, Yasuhiro; Matsuyama, Koushi; Oshima, Shuichi; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao; Investigators, Precise–Ivus

doi:10.1016/j.jacc.2015.05.065

Cited by 367 publications

(166 citation statements)

References 20 publications

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“…This result suggests that worsened clinical presentation and vulnerable plaque features at baseline may result in more favorable responses among nonculprit plaques to statin. Similar results were reported in several previous studies using intravascular ultrasonography and OCT 10, 38, 39. Takarada et al demonstrated that the efficacy of statin therapy on improving FCT, assessed by serial OCT, was significantly greater in plaques with thinner caps than in those with thicker caps 10.…”

Section: Discussionsupporting

confidence: 86%

“…In addition, most studies that tested the efficacy of statin therapy on plaque stabilization in patients with ACS demonstrated improvement in plaque phenotype 10, 11, 40, 41. Recently, Tsujita et al conducted a randomized trial to investigate the efficacy of additional ezetimibe intake over atorvastatin alone on changes in plaque volume over 9 to 12 months of follow‐up 39. They reported that plaque regression in the group treated with additional ezetimibe was greater in the ACS cohort than in the stable angina cohort.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Minami

Wang

Aguirre

et al. 2017

JAHA

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BackgroundPrevious studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin‐cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease.Methods and ResultsA total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin‐cap area (fibrous cap thickness, <200 μm) was measured using a novel 3‐dimensional computer‐aided algorithm. Overall, the thin‐cap area significantly decreased from baseline (median, 2.852 mm2; 25th–75th percentile, 1.023–6.157 mm2) to follow‐up (median, 1.210 mm2; 25th–75th percentile, 0.250–3.192 mm2; P<0.001), and low‐density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow‐up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin‐cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350–3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, −1.535 mm2; 95% confidence interval, −2.561 to −0.509 mm2; P=0.003).ConclusionsChronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Minami

Wang

Aguirre

et al. 2017

JAHA

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“…Recently, the PRECISE-IVUS (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial found that sterols (lathosterol, campesterol, and sitosterol) and their ratio to cholesterol increased with atorvastatin monotherapy but decreased with the atorvastatin-ezetimibe combination. Interestingly, the campesterol-to-cholesterol ratio reduction was positively related to a reduction in percent atheroma volume [20]. The notion that statin-ezetimibe combination therapy might reduce the variability in LDL-C-lowering response is also supported by a recent analysis of patient-level data pooled from 27 double-blind controlled studies [21].…”

Section: Variability In Individual Response To Statin Therapymentioning

confidence: 86%

“…As expected, the atorvastatin-ezetimibe combination resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 vs. 73.3 mg/dl; p \ 0.001). More importantly, a significantly greater percentage of patients who received atorvastatin-ezetimibe experienced coronary plaque regression (78 vs. 58%; p = 0.004) [20]. An interesting substudy of this trial showed that achieved LDL-C was the strongest independent predictor of reduction in coronary atheroma volume [79].…”

Section: Impact Of the Atorvastatin-ezetimibe Combination On The Progmentioning

confidence: 89%

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Ferreira

Silva

2016

Am J Cardiovasc Drugs

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Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

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“…Az ezetimibbel a 2002-ben történt bevezetése óta számos vizsgálatot végeztek, ezek közül a fentebb részletezett IMPROVE-IT hozott érté-kes evidenciákat: a szer hatékonyan csökkenti a cardiovascularis rizikót, 21%-kal csökkentve az ischaemiás stroke bekövetkeztének esélyét is [27]. Az 50% feletti LDL-C-szint-csökkenést, emellett az ezetimib haté-konyságát támasztotta alá a coronariaplakk-regresszió-ban több vascularis ultrahanggal elvégzett vizsgálat is [29,30].…”

Section: Az Ldl-koleszterin-szint Csökkentésének úJ Irányvonalaiunclassified

Lipidek és az agyérbetegség – Új lehetőségek az LDL-koleszterin-szint csökkentésére

et al. 2016

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A stroke világszerte a harmadik leggyakoribb halálok, a szívinfarktus és a daganatos betegségek után, funkcionális kimenetele pedig valamennyi betegség közül a legrosszabb. A koleszterin, különösen az LDL-C-szint kulcsszerepet játszik az érelmeszesedésben, a plakkok kialakulásában. Az elmúlt években bebizonyosodott, hogy az LDL-C-szint növekedésével arányosan emelkedik a cerebrovascularis betegségek incidenciája és halálozása. A statinterápia egyér-telműen csökkenti a stroke-rizikót, de a más módszerekkel elért lipidszintcsökkentő kezelésnek eddig nem volt igazoltan szignifikáns hatása. A magasabb dózisú statinkezelés preventív hatása egyértelmű, ugyanakkor az ilyen dózis alkalmazása fokozott óvatosságot igényel korábbi intracerebralis vérzést elszenvedett betegeknél, és kockáztathatjuk az új keletű diabetes kialakulását is. A közelmúltban közzétett IMPROVE-IT vizsgálat elsőként igazolta, hogy a statinterápia mellé adott nem statin típusú ezetimibbel az LDL-C-szint tovább csökkenthető, ezzel párhuzamosan tovább mérséklődik a cardio-és cerebrovascularis események incidenciája, a mellékhatások számának növekedése nélkül. Ezek az eredmények újra megerősítették a minél nagyobb mértékű LDL-C-szint-csökkentés jelentőségét. A statin-ezetimib kombináció révén a célértékek elérése alacsony és közepes statindózissal is lehetséges, csökkentve ezáltal a magas dózisú statinkezelés mellékhatásainak veszélyét. Orv. Hetil., 2016Hetil., , 157(52), 2059Hetil., -2065 Kulcsszavak: LDL-koleszterin, stroke, statinok, ezetimib Lipids and cerebrovascular disease -New therapeutic options in lowering LDL-cholesterolStroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a nonstatin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to hig...

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Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention

Cited by 367 publications

References 20 publications

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Lipidek és az agyérbetegség – Új lehetőségek az LDL-koleszterin-szint csökkentésére

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