pitavastatin and Acute-Coronary-Syndrome

Stains remain the first therapeutic approach in patients with dyslipidemia to control plasma lipids levels and cardiovascular risk. Multiple clinical trials have demonstrated the benefits of statins in reducing major cardiovascular adverse events in primary and secondary prevention. Moreover, in patients with coronary artery disease, statins decrease coronary atherosclerotic plaque volume and composition, inducing atheroma stabilization. Pitavastatin, is a new-generation lipophilic statin, indicated for the treatment of dyslipidemia and prevention of cardiovascular diseases. The purpose of this review, the first at our knowledge on this topic, is to summarize and examine the current knowledge about the effectiveness of pitavastatin in patients with coronary artery disease. The available data suggest that pitavastatin significantly, lowers the rate of adverse cardiovascular events, in patients at a high risk of atherosclerotic disease, with stable angina pectoris or with acute coronary syndrome. Moreover intravascular ultrasound have shown that pitavastatin induces favorable changes in plaque morphology, increasing the fibrous cap thickness, and decreasing both plaque and lipid volume indexes. Globally the efficacy of pitavastatin is greater or similar to other statins.

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Quinolines

Statins have proven beneficial for reducing both primary and secondary events in patients with coronary heart disease. Tight control of serum lipid parameters in these patients is recommended by the most recent clinical guidelines. Although numerous lipid-lowering treatments are available, only a small percentage of eligible patients receive therapy and fewer achieve their lipid-lowering goals. Thus it is clear that new treatment strategies to manage patients with lipid abnormalities are warranted. Pitavastatin (Lival; Kowa Pharmaceuticals America, Montgomery, AL, USA) has been recently approved for the treatment of hypercholesterolemia and combined dyslipidemia. Pitavastatin 1-4 mg/day has shown similar low-density lipoprotein-reducing activity to other commercially available statins, including simvastatin and atorvastatin. Adverse events occurred at similar rates to other statins in clinical trials with favorable effects seen in patients with dyslipidemia and metabolic syndrome. Pharmacokinetic drug-drug interactions are minimized due to the lack of significant metabolism of pitavastatin by the cytochrome P450 enzyme system, although some drugs affect its uptake into hepatocytes and should be avoided. In addition to its higher acquisition cost, pitavastatin has not been shown to improve clinical outcomes in high-risk patient populations and thus may not be the agent of choice in many patients at this time in lieu of cheaper, clinically proven alternatives.

Topics: Acute Coronary Syndrome; Comorbidity; Diabetes Mellitus; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Quinolines; Renal Insufficiency, Chronic

Topics: Acute Coronary Syndrome; Atorvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Pyrroles; Quinolines

The effects of high-sensitivity C-reactive protein (hs-CRP) levels on clinical outcomes in chronic-phase acute coronary syndrome (ACS) patients undergoing aggressive lipid-lowering therapy remain unclear. We examined the effects of hs-CRP levels on the prognosis of ACS patients who underwent aggressive lipid-lowering therapy and determined treatment targets for hs-CRP value.. This post-hoc sub-analysis of a prospective randomized control trial (HIJ-PROPER) included 1734 ACS patients with dyslipidemia, who were divided into hs-CRP quartiles after 3 months of treatment. Primary endpoints were combined all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. Secondary endpoint was all-cause death.. The median follow-up period was 3.7 years. Overall, 1415 patients were evaluated retrospectively. No significant among-group differences were noted in low-density lipoprotein cholesterol (LDL-C) levels over time (p = 0.44). Kaplan-Meier analyses revealed that the incidence of the primary and secondary endpoints was significantly higher in the highest hs-CRP group than in the other groups [hazard ratio (HR) = 1.52, 95% confidence interval (CI) = 1.16-2.00, p < 0.01; HR = 5.30, 95% CI = 2.47-11.32, p < 0.01, respectively]. The cut-off hs-CRP level to predict all-cause death was 0.74 mg/L (receiver operating characteristic curve: sensitivity: 68%, specificity: 62%). Multivariate analyses revealed that hs-CRP ≥0.74 mg/L　at 3 months was correlated with an increased risk of all-cause death (adjusted HR = 3.68, 95% CI = 2.22-6.10, p < 0.01).. Elevated hs-CRP levels independently predicted a worse prognosis, regardless of LDL-C levels, suggesting that interventions against elevated inflammatory responses plus intensive lipid-lowering therapy and coronary revascularization are encouraging options for secondary prevention in ACS patients.. This trial is registered with the UMIN Clinical Trials Registry number UMIN000002742. Trial name: Proper level of lipid lowering with pitavastatin and ezetimibe in acute coronary syndrome (HIJ-PROPER) URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr-view.cgi?recptno=R000003334.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; C-Reactive Protein; Dyslipidemias; Ezetimibe; Female; Humans; Male; Middle Aged; Quinolines; Single-Blind Method

This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events.. The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. The entire cohort was divided into three groups according to tertiles of HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, HDL-C >43, <53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups.. The primary endpoint event occurred in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively, and its incidence was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19-1.9; p = 0.001). Irrespective of the treatment regimen, Group 1 had significantly higher rates of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12-2.22; p = 0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05-1.98; p = 0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Multivariate analysis revealed that lower body mass index, prevalence of diabetes mellitus, higher levels of high-sensitivity C reactive protein at baseline, and lower levels of HDL-C at 3-month follow-up were independent predictors of the incidence of primary endpoint.. Lower levels of HDL-C at 3-month follow-up are independently associated with higher incidence of cardiovascular events in ACS patients receiving contemporary lipid-lowering therapy.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Cholesterol, HDL; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Quinolines; Treatment Outcome

Background This study aimed to examine the impact of baseline eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio on clinical outcomes of patients with acute coronary syndrome. Methods and Results In the HIJ-PROPER (Heart Institute of Japan Proper Level of Lipid Lowering With Pitavastatin and Ezetimibe in Acute Coronary Syndrome) study, 1734 patients with acute coronary syndrome and dyslipidemia were randomly assigned to pitavastatin+ezetimibe therapy or pitavastatin monotherapy. We divided the patients into 2 groups based on EPA/AA ratio on admission (cutoff 0.34 μg/mL as median of baseline EPA/AA ratio) and examined their clinical outcomes. The primary end point comprised all-cause death, nonfatal myocardial infarction, nonfatal stroke, unstable angina pectoris, or ischemia-driven revascularization. Percentage reduction of low-density lipoprotein cholesterol and triglyceride from baseline to follow-up was similar regardless of baseline EPA/AA ratio. Despite the mean low-density lipoprotein cholesterol level during follow-up being similar between the low- and high-EPA/AA groups, the mean triglyceride levels during follow-up were significantly higher in the low- than in the high-EPA/AA group. After 3 years of follow-up, the cumulative incidence of the primary end point in patients with low EPA/AA was 27.2% in the pitavastatin+ezetimibe group compared with 36.6% in the pitavastatin-monotherapy group (hazard ratio 0.69; 95% CI, 0.52-0.93; P=0.015). However, there was no effect of pitavastatin+ezetimibe therapy on the primary end point in patients with high EPA/AA (hazard ratio 0.92; 95% CI, 0.70-1.20; P=0.52). Conclusions Among acute coronary syndrome patients who have dyslipidemia and low EPA/AA ratio, adding ezetimibe to statin decreases the risk of cardiovascular events compared with statin monotherapy. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000002742.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Anticholesteremic Agents; Arachidonic Acid; Cholesterol, LDL; Drug Therapy, Combination; Dyslipidemias; Eicosapentaenoic Acid; Ezetimibe; Fatty Acids, Unsaturated; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Prognosis; Quinolines; Risk Assessment; Stroke

The aim of the present study was to assess the effect of early statin therapy on fibrous-cap thickness in coronary plaques of patients with acute coronary syndrome (ACS) by using optical coherence tomography.. Statins can contribute to the stabilization of coronary plaques.. This is a prospective, randomized, active-controlled, single-center study. Patients with ACS and untreated dyslipidemia were enrolled and randomly allocated (ratio 1:1) to either the early statin group (received pitavastatin 4 mg/day from baseline) or the late statin group (received pitavastatin 4 mg/day from 3 weeks after the baseline). Optical coherence tomography was performed at baseline, 3-week, and 36-week follow-up to assess nonculprit coronary plaques in 53 patients.. Between baseline and 3-week follow-up, fibrous-cap thickness increased in the early statin group (140 μm [interquartile range (IQR):120 to 170 μm] to 160 μm [IQR: 130 to 190 μm]; p = 0.017), but decreased in the late statin group (135 μm [IQR: 110 to 183 μm] to 130 μm [IQR: 108 to 160 μm]; p = 0.020). The percentage of increase in fibrous-cap thickness between baseline and 3-week follow-up was significantly greater in the early statin group compared with the late statin group (8.3% [IQR: 0.0% to 21.4%] vs. -5.8% [IQR: -16.0% to 0.0%]; p < 0.001). Between baseline and 36-week follow-up, fibrous-cap thickness increased comparably in the 2 groups.. Early therapy with pitavastatin 4 mg/day for patients with ACS provided an increase in fibrous-cap thickness in coronary plaques during the first 3 weeks of follow-up and a further increase during 36 weeks of follow-up. The study was registered with UMIN Clinical Trial Registry (Effect of PitavaStatin on Coronary Fibrous-cap Thickness-Assessment by Fourier-Domain Optical CoheRence Tomography [ESCORT]; UMIN000002678).

Topics: Acute Coronary Syndrome; Aged; Coronary Vessels; Female; Fibrosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Quinolines; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial.Methods and Results:We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naïve patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The primary endpoint was the percentage change in non-culprit coronary plaque volume (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n=53; between-group difference, 16.9%, P<0.0001). The percent change in PV was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups had reduction of PV compared with baseline (both P<0.01). The percent change in lipid PV did not differ between the groups (4.3 vs. -3.0%, P=0.37).. In statin-naïve patients with ACS, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone. [Clinical Trial Registration: www.clinicaltrials.gov (NCT00549926)].

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Cholesterol, LDL; Disease Progression; Drug Therapy, Combination; Ezetimibe; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Quinolines; Ultrasonography, Interventional

The systematic inflammatory response might confound renal impairment, and both have been reported to affect clinical outcomes after acute coronary syndrome. We examined the impacts of the high-sensitivity C-reactive protein (hsCRP) level and estimated glomerular filtration rate level on the prognosis for acute coronary syndrome patients who underwent aggressive lipid-lowering therapy in contemporary practice. This was a subanalysis of the HIJ-PROPER study, and 1,734 patients were enrolled. Patients were divided into 4 groups using an hsCRP value of 10mg/L and an estimated glomerular filtration rate value of 60 ml/min/1.73 m

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ezetimibe; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Prognosis; Prospective Studies; Quinolines; Renal Insufficiency; Single-Blind Method; Time Factors

To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L).. The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91).. Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed.. UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Anticholesteremic Agents; Cholesterol, LDL; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Non-ST Elevated Myocardial Infarction; Prospective Studies; Quinolines; ST Elevation Myocardial Infarction; Treatment Outcome

There is a residual risk of coronary heart disease (CHD) despite intensive statin therapy for secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by the addition of eicosapentaenoic acid (EPA) to high-dose pitavastatin (PTV).. We enrolled 193 CHD patients who underwent percutaneous coronary intervention (PCI) in six hospitals. Patients were randomly allocated to the PTV group (PTV 4mg/day, n=96) or PTV/EPA group (PTV 4mg/day and EPA 1800mg/day, n=97), and prospectively followed for 6-8 months. Coronary plaque volume and composition in nonstenting lesions were analyzed by integrated backscatter intravascular ultrasound (IB-IVUS).. The PTV/EPA group showed a greater reduction in total atheroma volume compared to PTV group. IB-IVUS analyses revealed that lipid volume was significantly decreased during follow-up period in only PTV/EPA group. The efficacy of additional EPA therapy on lipid volume reduction was significantly higher in stable angina pectoris (SAP) patients compared to acute coronary syndrome patients. EPA/AA ratio was significantly improved in PTV/EPA group compared to PTV group. There was no significant difference in the incidence of major adverse cardiovascular events and side effects.. Combination EPA/PTV therapy significantly reduced coronary plaque volume compared to PTV therapy alone. Plaque stabilization was also reinforced by EPA/PTV therapy in particular SAP patients. The addition of EPA is a promising option to reduce residual CHD risk under intensive statin therapy.

Topics: Acute Coronary Syndrome; Aged; Angina, Stable; Combined Modality Therapy; Eicosapentaenoic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Quinolines

In contrast to current guidelines in Western countries, moderate reduction of low-density lipoprotein cholesterol (LDL-C) is recommended for Japanese patients with atherosclerotic cardiovascular disease and dyslipidemia even in secondary prevention. HIJ-PROPER (Heart Institute of Japan-PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute coRonary syndrome) is a prospective, randomized, open-label, blinded endpoint multicenter trial designed to assess whether closely controlled LDL-C lowering with a standard statin dose plus ezetimibe, targeting LDL-C of <70mg/dL, would reduce cardiovascular events more than standard statin monotherapy targeting LDL-C of <100mg/dL as per the Japan Atherosclerotic Society guideline in patients with acute coronary syndrome (ACS) and dyslipidemia.. We recruited patients with ACS and dyslipidemia who had undergone coronary angiography. Participants are randomly allocated to either intensive LDL-C lowering treatment (target LDL-C of <70mg/dL; pitavastatin plus ezetimibe) or standard LDL-C lowering treatment (target LDL-C of 90-100mg/dL; pitavastatin monotherapy). The primary endpoint is a composite of total death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, and any ischemia-driven revascularization. Patients will be followed for a minimum of 3 years.. Between January 2010 and April 2013, 1734 patients were enrolled from 19 hospitals in Japan with a mean age of 65.6 years; 75.5% were men and 83.3% were statin-naïve. The qualifying ACS was an acute MI in 61.5%. This study is expected to report its findings in August 2016.. HIJ-PROPER will determine whether targeting LDL-C of <70mg/dL with pitavastatin plus ezetimibe can improve cardiovascular outcomes in Japanese patients with ACS and dyslipidemia in comparison to targeting LDL-C of 90-100mg/dL with standard pitavastatin monotherapy.. UMIN000002742.

Topics: Acute Coronary Syndrome; Aged; Cholesterol, LDL; Coronary Angiography; Drug Therapy, Combination; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Japan; Male; Middle Aged; Prospective Studies; Quinolines

Early initiation of EPA treatment in combination with a statin within 24h after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) reduces inflammation and ventricular arrhythmia compared with statin monotherapy; however, the impact of early initiation of EPA treatment on cardiovascular events is unclear. We determined whether early eicosapentaenoic acid (EPA) treatment in patients with acute coronary syndrome (ACS) reduces adverse cardiovascular events.. This prospective, open-label, blind end point-randomized trial consisted of 241 patients with ACS. Patients were randomly assigned to receive pitavastatin (2mg/day) with or without 1800mg/day of EPA initiated within 24h after PCI. The primary endpoint was defined as cardiovascular events occurring within 1year, including death from a cardiovascular cause, nonfatal stroke, nonfatal MI and revascularization.. The mean EPA/arachidonic acid ratio at follow-up was 0.40 in the control group and 1.15 in the EPA group. A primary endpoint event occurred in 11 patients (9.2%) in the EPA group and 24 patients (20.2%) in the control group (absolute risk reduction, 11.0%; hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.87; P=0.02). Notably, death from a cardiovascular cause at 1year was significantly lower in the EPA group than in the control group (0.8% vs. 4.2%, P=0.04).. Early initiation of treatment with EPA combined with statin after successful primary PCI reduced cardiovascular events after ACS.. UMIN Clinical Trials Registry (UMIN-CTR); Registry Number, UMIN000016723; URL, http://www.umin.ac.jp/ctr/index-j.htm.

Topics: Acute Coronary Syndrome; Aged; Drug Administration Schedule; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Quinolines; Treatment Outcome

Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Necrosis; Phenotype; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Ultrasonography, Interventional

The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients.. Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA(1c).. The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.

Topics: Acute Coronary Syndrome; Aged; Analysis of Variance; Atorvastatin; Biomarkers; Body Mass Index; Chi-Square Distribution; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Female; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Linear Models; Male; Metabolic Syndrome; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prospective Studies; Pyrroles; Quinolines; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography, Interventional

To clarify whether the effects of statin treatment on plaque regression vary according to the presence or absence of polyvascular disease (PVD) in patients with acute coronary syndrome (ACS).. 307 patients with ACS who underwent percutaneous coronary intervention for the culprit lesion at 33 centers were treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was defined as coexistent, clinically recognized arterial disease other than coronary artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at baseline and at 8-12 months follow-up. Serial IVUS examinations were obtained in 252 patients. Atheroma volume and percent change in atheroma volume of the target plaque was assessed.. Patients of the CAD+PVD (n = 19) were older (68 vs. 62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels at baseline (116 vs. 134 mg/dL, p=0.03) than those of the CAD-only group (n = 233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although the baseline plaque volume was similar in the two groups (59 vs. 57 mm(3)), patients of the CAD+PVD group showed milder regression of atherosclerosis than those of the CAD-only group (-8.9% vs. -18.2%, p = 0.005). This difference remained significant even after adjustment for coronary risk factors including age and serum LDL-C (p = 0.047).. Statin treatment results in milder regression of coronary atherosclerosis in CAD patients with polyvascular disease compared to those with CAD only.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherosclerosis; Atorvastatin; Chi-Square Distribution; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Pyrroles; Quinolines; Regression Analysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Acute Coronary Syndrome; Atorvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Pyrroles; Quinolines

The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial has found that early aggressive statin therapy in patients with acute coronary syndrome (ACS) significantly reduces the plaque volume (PV) of non-culprit coronary lesions. The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy.. Serial intravascular ultrasound observations over 8-12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin. Linear regression analysis identified the presence of diabetes mellitus (DM) and PV at baseline as inhibiting factors, and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression. Significant correlation between % change of PV and low-density lipoprotein cholesterol (LDL-C) level was found in patients with DM (n=73, P<0.05, r=0.4), whereas there was no significant correlation between the 2 parameters in patients without DM (n=178).. The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts. Moreover, vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM.

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Coronary Artery Disease; Diabetes Mellitus; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pyrroles; Quinolines; Treatment Outcome; Ultrasonography, Interventional

We have shown that aggressive lipid lowering by pitavastatin and atorvastatin results in marked regression of atherosclerotic coronary lesions after acute coronary syndrome (ACS). The purpose of this study was to address the association of lipid levels after statin therapy with regression of atherosclerotic coronary lesions and major cardiovascular events in patients after ACS.. JAPAN-ACS is a prospective, randomized open-label study performed at 33 centers in Japan. Patients with ACS undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were randomly assigned to receive either 4 mg/day pitavastatin or 20 mg/day atorvastatin within 72 hours after PCI. IVUS image was obtained in 251 patients, including 73 diabetic patients. Lipid profiles at the end of the study were divided into quartiles and the association with the percent change in non-culprit coronary plaque volume (PV) was assessed in total and diabetic patients. We also studied whether baseline and follow-up levels of HDL-cholesterol are associated with restenosis after PCI.. Decreasing LDL-cholesterol, non-HDL-cholesterol, LDL-C/HDL-C ratio, apolipoprotein B quartiles were associated with a progressively smaller plaque burden in total and diabetic patients. In diabetic patients, further reduction of these parameters was associated with a significantly greater reduction in PV. We also found that patients with lower HDL-cholesterol had a significantly higher incidence of target lesion revascularization.. Early intensive statin therapy in patients after ACS results in remarkable regression of coronary PV. Diabetic patients can have a benefit with more intensive therapy to achieve a lower target level in Japanese.

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Prospective Studies; Pyrroles; Quinolines; Treatment Outcome; Ultrasonography, Interventional

The Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering therapy with a statin resulted in a significant regression of coronary atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived protein with anti-atherogenic properties. Here, we investigated the association between adiponectin levels and the change in the plaque volume in ACS patients.. Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and 12 months after the PCI. The percent change in the plaque volume (%PV) in a non-culprit coronary artery segment was evaluated. The serum adiponectin and lipid parameters were measured both at baseline and at the follow-up.. At baseline, adiponectin was correlated positively with HDL-cholesterol and negatively correlated with triglyceride, but no correlation was observed with the PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in adiponectin was also associated with an increase of HDL-cholesterol and decrease of triglyceride, however, no significant correlation was observed with the %PV. A significantly higher incidence of major adverse cardiac events (MACE) was observed in patients with hypo-adiponectinemia at baseline. A multiple logistic regression analysis identified adiponectin as a significant independent predictor of MACE.. Adiponectin levels measured after PCI could serve as a marker of MACE in patients with ACS.

Topics: Acute Coronary Syndrome; Adiponectin; Aged; Angioplasty, Balloon, Coronary; Atorvastatin; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Coronary Vessels; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Logistic Models; Male; Middle Aged; Odds Ratio; Prospective Studies; Pyrroles; Quinolines; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Ultrasonography, Interventional; Up-Regulation

The objective of this study was to evaluate whether the regressive effects of aggressive lipid-lowering therapy with atorvastatin on coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) are generalized for other statins in multicenter setting.. A previous single-center study reported beneficial regressive effects of atorvastatin in patients with ACS on PV of the nonculprit site by intravascular ultrasound (IVUS) evaluation. The effect of statins other than atorvastatin on PV has not been evaluated in the setting of ACS.. The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study was a prospective, randomized, open-label, parallel group study with blind end point evaluation conducted at 33 centers in Japan. A total of 307 patients with ACS undergoing IVUS-guided percutaneous coronary intervention were randomized, and 252 patients had evaluable IVUS examinations at baseline and 8 to 12 months' follow-up. Patients were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin. The primary end point was the percentage change in nonculprit coronary PV.. The mean percentage change in PV was -16.9 +/- 13.9% and -18.1 +/- 14.2% (p = 0.5) in the pitavastatin and atorvastatin groups, respectively, which was associated with negative vessel remodeling. The upper limit of 95% confidence interval of the mean difference in percentage change in PV between the 2 groups (1.11%, 95% confidence interval: -2.27 to 4.48) did not exceed the pre-defined noninferiority margin of 5%.. The administration of pitavastatin or atorvastatin in patients with ACS equivalently resulted in significant regression of coronary PV (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome; NCT00242944).

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Coronary Artery Disease; Coronary Vessels; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pyrroles; Quinolines; Treatment Outcome; Ultrasonography, Interventional

We determined time course of stabilization of echolucent carotid plaques by statin therapy in patients with acute coronary syndrome (ACS). Treatment with 4 mg/d pitavastatin (n = 33) or placebo (n = 32) was initiated within 3 days after onset of ACS in 65 patients with echolucent carotid plaque. Vulnerable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) analysis before and 1 month after treatment in all patients. The calibrated IBS value (intima-media IBS value minus adventia IBS) of vulnerable carotid plaques favorably changed at 1 month after treatment in both groups, but the echolucency at 1 month improved more in the pitavastatin than in the placebo group (pitavastatin group: -18.7 +/- 3.3 dB at pretreatment versus -12.7 +/- 2.3 dB at 1 month *P < 0.001; placebo: -19.0 +/- 3.5 dB versus -16.9 +/- 3.2 dB, P < 0.05, *P < 0.01 versus the value at 1 month in placebo group). Levels of CRP, VEGF, and TNFalpha at 1 month were significantly lower in pitavastatin than placebo group. In conclusion, pitavastatin improved carotid plaque echolucency within 1 month of therapy in patients with ACS, in association with decrease in the inflammatory biomarkers related to vulnerable plaques.

Topics: Acute Coronary Syndrome; C-Reactive Protein; Carotid Stenosis; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Prospective Studies; Quinolines; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha; Ultrasonography; Vascular Endothelial Growth Factor A

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Phenotype; Plaque, Atherosclerotic; Quinolines; Tomography, Optical Coherence

We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia.. This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined.. The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy.. Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Predictive Value of Tests; Quinolines; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Sitosterols; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Humans; Prospective Studies; Quinolines; Risk Factors

Topics: Acute Coronary Syndrome; Atorvastatin; Evaluation Studies as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Quinolines

Matrix metalloproteinases (MMPs) have been implicated in development of atherosclerosis. MMPs are activated in patients with acute coronary syndrome (ACS). However, little data exist regarding the correlation between circulating levels of MMPs and plaque volume (PV) in patients with ACS. We therefore evaluated the impact of MMPs on coronary PV as a post hoc analysis from the JAPAN-ACS study.. The multicenter JAPAN-ACS trial revealed that aggressive statin therapy for patients with ACS significantly reduces coronary PV determined by intravascular ultrasound (IVUS). We studied 248 ACS patients who had serial IVUS examinations over 8-12 months in the trial. For each patient, MMP-1, 2, and 3 were measured both at baseline and at study end to evaluate the correlation between the percent change of PV and MMP levels.. MMP-3 levels were significantly decreased during the follow-up period (100 ng/mL to 73 ng/mL, p < 0.001), in contrast, MMP-1, -2 levels were significantly increased. MMP-3 levels at follow-up correlated with coronary plaque regression (p for trend = 0.016). A multivariable linear regression model showed both MMP-2 and MMP-3 levels at follow-up were independent variables for change of coronary PV (p = 0.038 and p = 0.016, respectively).. Circulating MMPs levels are associated with changes in coronary plaque volume determined by serial IVUS in patients with ACS.

Topics: Acute Coronary Syndrome; Atorvastatin; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinases; Middle Aged; Plaque, Atherosclerotic; Prospective Studies; Pyrroles; Quinolines; Remission Induction

Topics: Acute Coronary Syndrome; Atorvastatin; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Plaque, Atherosclerotic; Pyrroles; Quinolines

The JAPAN-ACS study demonstrated that statins significantly reduced coronary plaque volume in patients with acute coronary syndrome (ACS). The clinical implications of plaque regression for clinical outcomes in ACS patients has not been established. The Extended JAPAN-ACS study was conducted to evaluate the relationship between coronary plaque regression and long-term clinical outcome, and to explore the factors associated with cardiovascular events.. Patients with intravascular ultrasound (IVUS) data at both enrollment and follow-up in the JAPAN-ACS study were enrolled and observed for at least 3 years. Patients were divided into lesser and greater coronary plaque regression groups. The primary endpoint was defined as a composite of the following events: cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, and unstable angina. The median value of the percent change in plaque volume, 18.0%, was used as a cutoff point. There were 4 primary events (3.4%) in the lesser regression group, and 2 events (1.7%) in the greater regression group (P=0.4). Cumulative secondary cardiovascular events did not differ between the 2 groups. Multivariate analysis identified the high-density lipoprotein cholesterol (HDL-C) at baseline and the % change of the external elastic membrane volume as independent risk factors of cardiovascular events.. Coronary plaque regression induced by an intensive statin regimen did not predict future cardiovascular events in ACS patients. Rather, the baseline HDL-C level and reverse vessel remodeling might serve as predictors for cardiovascular events.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Atorvastatin; Biomarkers; Cerebral Infarction; Cholesterol, HDL; Coronary Artery Disease; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Plaque, Atherosclerotic; Predictive Value of Tests; Proportional Hazards Models; Pyrroles; Quinolines; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Acute Coronary Syndrome; Atorvastatin; Coronary Artery Disease; Coronary Vessels; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolic Syndrome; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Pyrroles; Quinolines

Topics: Acute Coronary Syndrome; Atorvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrroles; Quinolines; Reproducibility of Results; Treatment Outcome; Ultrasonography, Interventional