pitavastatin and Coronary-Artery-Disease

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 are the first line of therapy to reduce low-density lipoprotein cholesterol (LDL-C) in order to decrease cardiovascular events. Pitavastatin is the latest statin to be introduced to the market. Areas covered: In this article, the authors review the efficacy, safety, and tolerability of pitavastatin. The authors also review a recent cardiovascular outcome study. Expert opinion: Pitavastatin produces dose-dependent reductions in LDL-C at lower doses than other statins. The maximum approved dose of 4 mg reduces LDL-C by about 40-49% in different patient groups and is equivalent to atorvastatin 20 mg in this effect. Pitavastatin undergoes minimal metabolism so drug-drug interactions are less likely than with many other statins, but it can interact with some drugs that inhibit drug transporters. Compared with other statins, it has been associated with greater increases in high-density lipoprotein cholesterol and it was found to be less likely to cause new onset diabetes. In a recent study in Japanese patients with stable coronary artery disease, pitavastatin 4 mg was more effective than pitavastatin 1 mg in reducing cardiovascular events. Therefore, the highest dose may be preferred in high-risk patients.

Topics: Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines; Treatment Outcome

The aim of this study is to compare the efficacy and safety of pitavastatin and atorvastatin using data from randomized-controlled trial pooled together by means of a meta-analysis and decide which is better.. PubMed, CENTRAL, Web of Knowledge, and ClinicalTrials.gov website were searched for randomized-controlled trials published until October 2016. Eligible studies comparing pitavastatin with atorvastatin head to head and reporting the outcome of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glycated hemoglobin, and intravascular ultrasound evaluation were enrolled. Heterogeneity was assessed by using the I statistic, and the extracted data were estimated by fixed-effects model.. Eleven trials including a total number of 1733 participants were identified. Compared with atorvastatin, changes in the mean differences of LDL-C and HDL-C were 2.51 [95% confidence interval (CI): 1.17-3.86; I=48%; P=0.0003] and 2.17 (95% CI: 1.42-2.91; I=40%; P<0.00001), respectively, for pitavastatin. The changes in the mean differences of glycated hemoglobin was -0.15 (95% CI: -1.44-1.15; I=0%; P=0.83) for pitavastatin compared with atorvastatin. For plaque volume, lumen volume, and external elastic membrane, the changes are -0.93 (95% CI: -3.04-1.19; I=50%; P=0.39), 0.17 (95% CI: -2.91-3.26; I=0%; P=0.91), and -0.43 (95% CI: -1.96-1.11; I=4%; P=0.58), respectively, for pitavastatin versus atorvastatin.. In this study, pitavastatin seems to be less effective in reducing LDL-C and elevating HDL-C level compared with atorvastatin. Moreover, there is no significant difference in changes of glycated hemoglobin and intravascular ultrasound evaluation between pitavastatin and atorvastatin.

Topics: Aged; Atorvastatin; Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Dyslipidemias; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Quinolines; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Ultrasonography, Interventional

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, have revolutionized the treatment of hypercholesterolemia and coronary artery disease prevention. However, there are considerable issues regarding statin safety and further development of residual risk control, particularly for diabetic and metabolic syndrome patients. Pitavastatin is a potent statin with low-density lipoprotein (LDL) cholesterol-lowering effects comparable to those of atorvastatin or rosuvastatin. Pitavastatin has a high-density lipoprotein (HDL) cholesterol raising effect, may improve insulin resistance, and has little influence on glucose metabolism. Considering these factors along with its unique pharmacokinetic properties, which suggest minimal drug-drug interaction, pitavastatin could provide an alternative treatment choice, especially in patients with glucose intolerance or diabetes mellitus. Many clinical trials are now underway to test the clinical efficacy of pitavastatin in various settings and are expected to provide further information.

Topics: Animals; Coronary Artery Disease; Diabetes Mellitus; Drug Interactions; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Quinolines

Atherogenic dyslipidemia is characterised by high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and moderate to marked elevations in low-density lipoprotein-cholesterol (LDL-C) concentrations; such dyslipidemia is further characterised by high apolipoprotein B (apoB): apolipoprotein A1 (apoA1) ratios. Numerous clinical trials have demonstrated that statins are effective in lowering LDL-C and reducing cardiovascular (CV) risk in people with dyslipidemia. However, the most effective treatments should target all of the key atherogenic features, rather than LDL-C alone. Pitavastatin is a new member of the statin class whose distinct pharmacological features translate into a broad spectrum of action on both apoB-containing and apoA1-containing lipoprotein components of the atherogenic lipid profile. The efficacy and safety of this statin has been demonstrated by a large clinical development programme conducted both in Japanese and Caucasian populations. Phase III and IV studies in a wide range of patients with primary hypercholesterolemia or combined dyslipidemia showed that 12 weeks' treatment with pitavastatin l-4 mg was well tolerated, significantly improved lipid profiles (including LDL-C, TG, and HDL-C levels) and increased the EAS-/NCEP ATP Ill-recommended LDL-C target attainment rate to a similar or greater degree as comparable doses of atorvastatin, simvastatin, or pravastatin. Results were similar across all patient groups and were generally sustained after 52 weeks of treatment. However, whereas the effects of atorvastatin and simvastatin on HDL-C levels remained constant over the long term, pitavastatin-treated patients experienced progressive and maintained elevations in HDL-C, ultimately increasing by up to 14.3% vs. initial baseline. In this context, it is significant that the in vitro studies of Yamashita et al. [J Atheroscler Thromb 2010;17:436-51] have shown pitavastatin to be distinguished by its potent stimulation of apoA1 production in hepatocyte-like cells. These findings suggest that pitavastatin may be highly efficacious in raising levels of lipid-poor apoA1 particles, which are known to be highly active in ABCA1-mediated cellular cholesterol efflux, an observation which is pertinent to the excessive accumulation of cholesterol in macrophage foam cells of the atherosclerotic plaque. Indeed, the intravascular remodelling and maturation of lipid-poor apoA1 particles is known to drive flux of apoA1, ch

Topics: Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Coronary Artery Disease; Double-Blind Method; Dyslipidemias; Europe; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Lipids; Multicenter Studies as Topic; Plaque, Atherosclerotic; Pyrroles; Quinolines; Randomized Controlled Trials as Topic; Russia; Simvastatin; Triglycerides

This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin.. This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline.. A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001).. Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.

Topics: Biomarkers; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin I

The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients.. From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively.. During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months.. After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.

Topics: Aged; Angina, Unstable; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Coronary Artery Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Stroke; Male; Middle Aged; Myocardial Infarction; Quinolines; Risk Factors

It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction.. The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m. Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

Topics: Aged; Angina, Stable; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, LDL; Coronary Artery Disease; Female; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; Prospective Studies; Quinolines; Treatment Outcome

People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown.. REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally.. To date the Mechanistic Substudy has completed planned enrollment, with 805 participants.. This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.

Topics: Adult; Aged; Anti-HIV Agents; Biomarkers; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Plaque, Atherosclerotic; Primary Prevention; Prospective Studies; Quinolines; Risk Factors

The effect of lipid-lowering agents on progression of coronary artery calcification (CAC) remains unclear. We evaluated the effects of pitavastatin 2 mg/day (PIT2), pitavastatin 4 mg/day (PIT4), and PIT2 combined with eicosapentaenoic acid (PIT2+EPA) on CAC progression.Methods and Results:This prospective multicenter study in Japan included patients with an Agatston score of 1-999, hypercholesterolemia, and no evidence of cardiovascular disease. Patients were allocated into PIT2, PIT4, or PIT2+EPA groups. The primary outcome was the annual percent change in Agatston score in all patients. In total, 156 patients who had multi-detector row computed tomography without any artifacts were included in the primary analysis. Pitavastatin did not significantly reduce the annual progression rate of the Agatston score (40%; 95% CI: 19-61%). The annual progression rate of Agatston score in the PIT2 group was not significantly different from that in the PIT4 group (34% vs. 42%, respectively; P=0.88) or the PIT2+EPA group (34% vs. 44%, respectively; P=0.80). On post-hoc analysis the baseline ratio of low- to high-density lipoprotein cholesterol was a significant predictor of non-progression of Agatston score by pitavastatin (OR, 2.17; 95% CI: 1.10-44.12; P=0.02).. Pitavastatin does not attenuate progression of CAC. Intensive pitavastatin treatment and standard treatment with EPA does not reduce progression of CAC compared with standard treatment.

Topics: Aged; Cholesterol, LDL; Coronary Artery Disease; Disease Progression; Eicosapentaenoic Acid; Female; Humans; Japan; Male; Middle Aged; Prospective Studies; Quinolines; Treatment Outcome; Vascular Calcification

Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD.REAL-CAD is a prospective, multicenter, randomized, open-label, blinded-endpoint, physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group and 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event, including CV death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients and the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit.After the study is completed, we will have categorical evidence on the optimal statin dose and target LDL-C level for secondary prevention in Japanese patients.

Topics: Aged; Asian People; Coronary Artery Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Prospective Studies; Quinolines; Research Design

Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population.. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention.. High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

Topics: Aged; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Coronary Artery Disease; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Japan; Male; Middle Aged; Prospective Studies; Quinolines; Risk Assessment; Risk Factors; Time Factors; 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

This study aimed to clarify the relationships between arterial remodeling patterns and plaque volume regression or stabilization. The TOGETHAR trial is a prospective open-label trial designed to assess coronary plaque regression and stabilization with multiple plaque imaging modalities following 52 weeks of pitavastatin treatment (2 mg/day). Coronary plaques were observed in 46 patients with both angioscopy and intravascular ultrasound at baseline and after 52 weeks of drug treatment. We divided these patients into three groups according to their remodeling indices (RI). Group P consisted of patients with a baseline RI >1.05, Group M of patients with a baseline RI of 0.95-1.05, and Group N of patients with a baseline RI <0.95 and then evaluated differences in coronary plaque volume changes and yellow grade among the three groups. In the positive remodeling group, whose remodeling index (RI) exceeded 1.05 at baseline, RI and percent atheroma volume (PAV) were significantly reduced (RI 1.14 ± 0.07 to 1.05 ± 0.10, p = 0.010, PAV 47.3 ± 8.3 to 45.3 ± 7.3 mm(3), p = 0.048). There was no relationship between baseline RI and the change in yellow grade of plaque. RI increased without significant change of PAV or a decrease in lumen volume in group N, with RI below 0.95 at baseline. Plaques with positive remodeling were more likely to have plaque volume regression by pitavastatin than those without in patients with coronary artery disease. Moreover, plaques with positive and negative remodeling were changed into those with intermediate remodeling by pitavastatin. Pitavastatin might induce not only plaque regression or stabilization, but also conformational normalization of vessel structure.

Topics: Aged; Angioscopy; Coronary Artery Disease; Coronary Vessels; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Japan; Male; Middle Aged; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Quinolines; Remission Induction; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Remodeling

 Levels of platelet reactivity in patients on dual antiplatelet therapy (DAPT) can be influenced by concomitant treatment with statins. We verified if the pharmacodynamic effects of CYP3A4-metabolized statins (atorvastatin) and non-CYP3A4-metabolized statins (pitavastatin) differ in patients with coronary artery disease (CAD) treated with DAPT..  A total of 155 CAD patients receiving DAPT (clopidogrel 75mg plus aspirin 100mg) entered the PORTO trial. Patients were randomly assigned to atorvastatin (20mg day) or pitavastatin (4mg day) for 30 days, and then switched to the other drug for 30 days. Platelet reactivity was expressed as VerifyNow P2Y12 platelet response units (PRU) before and after each 30-day treatment period. High platelet reactivity was defined as PRU >208. As compared with pretreatment (192±49), PRU was significantly higher after 30-day atorvastatin (210±56; P=0.003), but was unchanged after 30-day pitavastatin (199±47 PRU, NS). In the 48 patients with PRU >208 at baseline (232±44), PRU increased significantly after 30-day atorvastatin (258±41, P=0.004), but not after 30-day pitavastatin (237±43, NS). In the 107 patients with PRU <208 at baseline (174±52), PRU did not change significantly with respect to baseline either after 30-day atorvastatin (188±61, NS) or after 30-day pitavastatin (181±59, NS)..  Pitavastatin, a non-CYP3A4-metabolized statin, does not affect clopidogrel's response as compared with atorvastatin in patients who are borderline or poor responders to DAPT. 

Topics: Aged; Aged, 80 and over; Aspirin; Atorvastatin; Clopidogrel; Coronary Artery Disease; Cross-Sectional Studies; Cytochrome P-450 CYP3A; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrroles; Quinolines; Ticlopidine

Many clinical trials have shown that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can significantly reduce coronary artery disease in both primary and secondary prevention. A recent study showed that aggressive lipid-lowering therapy with strong statins could achieve coronary artery plaque regression, as evaluated with gray-scale intravascular ultrasound (IVUS). However, it is unknown whether coronary plaque regression and stabilization are reinforced when eicosapentaenoic acid (EPA) is used with a strong statin.. We aim to assess patients with stable angina or acute coronary syndrome who had undergone successful percutaneous coronary intervention (PCI) with integrated backscatter IVUS (IB-IVUS) guidance. They will be randomly allocated to receive pitavastatin (4mg), or pitavastatin (4mg) plus EPA (1800mg), and prospectively followed for 6-8 months.. The primary endpoint will be changes in tissue characteristics in coronary plaques, evaluated by IB-IVUS, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels, and inflammatory markers. The safety profile will also be evaluated.. The combination therapy of EPA and pitavastatin for regression of coronary plaque evaluated by IB-IVUS (CHERRY) study will be the first multicenter study using IB-IVUS to investigate the effects of combination therapy with pitavastatin and EPA on coronary plaque volume and tissue characteristics.

Topics: Coronary Artery Disease; Coronary Vessels; Drug Therapy, Combination; Eicosapentaenoic Acid; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Prospective Studies; Quinolines; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein cholesterol levels. Although statins increase serum PCSK9 levels, the effects of different types of statins on the serum PCSK9 levels have not been examined in detail. The purpose of the present study was to compare the effects of pitavastatin versus pravastatin on the serum PCSK9 levels. A total of 164 patients with coronary artery disease who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin (intensive lipid-lowering therapy) or 20 mg/day of pravastatin (moderate lipid-lowering therapy). The serum PCSK9 levels were measured before statin treatment and 8 months after therapy. A significantly greater reduction in low-density lipoprotein cholesterol was observed in the pitavastatin group (-41% vs -28%, p = 0.0001). The serum levels of total PCSK9 and heterodimer PCSK9 significantly increased from 192 to 249 ng/ml (37%, p <0.0001) and 147 to 206 ng/ml (78%, p <0.0001) in the pitavastatin group and from 192 to 249 ng/ml (39%, p <0.0001) and 143 to 201 ng/ml (65%, p <0.0001) in the pravastatin group, respectively. The increase in total and heterodimer PSCK9 did not differ between the 2 groups. No significant correlations were found between the percentage of changes in heterodimer PCSK9 and changes in the various lipid parameters in either group. In conclusion, significant increases in the total and heterodimer PSCK9 levels were observed at 8 months after treatment with pitavastatin and pravastatin; however, these increases did not differ between the 2 statins.

Topics: Aged; Apoptosis; Biomarkers; Coronary Artery Disease; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pravastatin; Proprotein Convertase 9; Proprotein Convertases; Prospective Studies; Quinolines; Serine Endopeptidases; Severity of Illness Index; Treatment Outcome

A low n-3 to n-6 polyunsaturated fatty acid (PUFA) ratio is associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined, particularly in patients treated with different types of statins. This study compared the effects of n-3 to n-6 PUFA ratios on coronary atherosclerosis in patients treated with pitavastatin and pravastatin. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Pitavastatin and pravastatin were used to treat 51 and 50 patients, respectively. Changes in the docosahexaenoic acid (DHA)/arachidonic acid (AA) and eicosapentaenoic acid+DHA/AA ratios were not correlated with the percentage change in plaque volume in the pitavastatin group, whereas the percentage change in plaque volume and the changes in the DHA/AA ratio (r = -0.404, p = 0.004) and eicosapentaenoic acid+DHA/AA ratio (r = -0.350, p = 0.01) in the pravastatin group showed significant negative correlations. Multivariate regression analysis showed that age (β = 0.306, p = 0.02), the presence of diabetes mellitus (β = 0.250, p = 0.048), and changes in the DHA/AA ratio (β = -0.423, p = 0.001) were significant predictors of the percentage change in plaque volume in patients treated with pravastatin. In conclusion, decreases in n-3 to n-6 PUFA ratios are associated with progression in coronary atherosclerosis during pravastatin therapy but not during pitavastatin therapy.

Topics: Aged; Atherosclerosis; Biomarkers; Coronary Artery Disease; Dose-Response Relationship, Drug; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Percutaneous Coronary Intervention; Pravastatin; Prospective Studies; Quinolines; Severity of Illness Index; Treatment Outcome; Ultrasonography, Interventional

Many large-scale clinical trials have confirmed that statins are effective in reducing low-density lipoprotein cholesterol (LDL-C) level, resulting in reducing cardiovascular events. Recent studies have focused on the effects of statins on high-density lipoprotein cholesterol (HDL-C). Here we compared the effects of two statins on lipid profile and other metabolic parameters.. The study population included 129 patients with stable coronary artery disease, hypercholesterolemia, and hypo-HDL-cholesterolemia (HDL-C<50mg/dl). They were randomly allocated to treatment by pitavastatin 2-4 mg/day or atorvastatin 10-20mg/day and followed-up for 30 months. The primary endpoint was percent changes in HDL-C and adiponectin during the study. The secondary endpoints were percent and absolute changes in markers of glucose metabolism, serum lipids, and apolipoproteins.. The effects of 30-month treatment with pitavastatin on HDL-C were significantly greater than those of atorvastatin (%change: pitavastatin: 20.1 ± 25.7%, atorvastatin: 6.3 ± 19.8%, p=0.01; absolute change: pitavastatin: 7.3 ± 9.1mg/dl, atorvastatin: 2.3 ± 8.0mg/dl, p=0.02). A similar trend was seen with regard to apolipoprotein-AI (ApoAI) (%change: pitavastatin: 20.8 ± 19.3%, atorvastatin: 11.4 ± 17.6%, p=0.03; absolute change: pitavastatin: 23.1 ± 20.2mg/dl, atorvastatin: 12.1 ± 19.4 mg/dl, p=0.02). Treatment with pitavastatin, but not atorvastatin, significantly increased adiponectin levels. Neither statin had a significant effect on hemoglobin A1c. No severe adverse events were registered during the study.. Long-term treatment with pitavastatin resulted in significantly greater increases in serum HDL-C and ApoAI levels without adverse effects on glucose metabolism, compared with atorvastatin.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Apolipoprotein A-I; Atorvastatin; Cholesterol, HDL; Coronary Artery Disease; Endpoint Determination; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Pyrroles; Quinolines; Young Adult

The TRUTH trial demonstrated that 8-month statin therapy alters the composition of coronary artery plaque using virtual histology (VH)-intravascular ultrasound (IVUS). The extended TRUTH study was conducted to evaluate the relationship between changes in coronary atherosclerosis and mid-term clinical outcomes and identify the factors associated with cardiovascular events.. Of 164 patients with angina pectoris who participated in the TRUTH trial, 119 subjects with analyzable IVUS data at both enrollment and the 8-month follow-up were enrolled and observed for at least two years. The primary end point was the time to first occurrence of cardiovascular composite events, including cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, unstable angina and ischemic-driven revascularization, except for target lesion revascularization.. The frequency of reaching the primary end point was 13% (16/119), with a mean follow-up period of 41.9±9.4 months. Although plaque regression and changes in plaque composition were not associated with future cardiovascular events, the serum high-sensitivity C-reactive protein (hs-CRP) levels at the start of the extended TRUTH study were significantly higher in the event group than in the event-free group (1.43 mg/L vs. 0.58 mg/L, p=0.01). A multivariate logistic regression analysis showed that the hs-CRP level was an independent significant predictor of cardiovascular events (odds ratio: 1.69; 95% confidence interval: 1.14-2.50, p=0.01).. Coronary artery plaque regression and changes in plaque composition during statin therapy do not predict future cardiovascular events in patients with angina pectoris. Instead, the serum hs-CRP level can be used as a predictor of cardiovascular events.

Topics: Aged; Angina Pectoris; C-Reactive Protein; Cardiovascular Diseases; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemia; Japan; Male; Middle Aged; Myocardial Infarction; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Regression Analysis; Risk Factors; Treatment Outcome; Ultrasonography, Interventional

Recent trials using intravascular ultrasound (IVUS) have shown that statins induce regression and stabilization of coronary artery plaques. However, there are no reports on whether regression and stabilization in coronary artery plaques associated with statin therapy continue or not. The purpose of the present study was to examine the time course of statin-induced changes in coronary atherosclerosis.. Coronary atherosclerosis was evaluated using virtual histology-IVUS in 39 patients at the time of a percutaneous coronary intervention, 8 months after statin therapy (mid-term), and at 48-month (long-term) follow-up. IVUS images qualified for evaluation obtained from 30 of these patients at three time points.. Significant decreases in low-density lipoprotein cholesterol and high-sensitivity C-reactive protein were observed at 8 months and these decreases continued for 48 months. A decrease in external elastic membrane volume was observed at 8 months (-1.1%) and reached significance at 48 months (-5.9%, P=0.0001). Plaque volume tended to decrease over time, but this was not statistically significant (-1.6% at 8 months and -3.8% at 48 months). An increase in the calcified plaque component was observed at 8 months (0.09±0.34 mm/mm) and reached significance at 48 months (0.21±0.33 mm/mm, P=0.002). Change in the calcified component and change in the external elastic membrane volume showed a significant negative correlation at the long-term follow-up (r=-0.598, P=0.0005).. Continued negative vessel remodeling associated with an increase in the calcified plaque component was observed following prolonged statin therapy by serial virtual histology-IVUS analysis.

Topics: Aged; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Linear Models; Male; Middle Aged; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Quinolines; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification

Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.. Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = -35.0 ± 14.1% and atorvastatin group = -38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (-37.1 ± 12.9% vs. -38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.. Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.. ClinicalTrials.gov NCT01386853 http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Lipoproteins; Male; Middle Aged; Pyrroles; Quinolines; Risk Factors; Treatment Outcome; Triglycerides

A low ratio of n-3 to n-6 polyunsaturated fatty acids has been associated with cardiovascular events. However, the effects of this ratio on coronary atherosclerosis have not been fully examined. The purpose of the present study was to evaluate the correlations between the n-3 to n-6 polyunsaturated fatty acid ratio and coronary atherosclerosis. Coronary atherosclerosis in nonculprit lesions in the percutaneous coronary intervention vessel was evaluated using virtual histology intravascular ultrasound in 101 patients at the time of percutaneous coronary intervention and 8 months after statin therapy. Forty-six patients (46%) showed atheroma progression and the remaining 55 patients (54%) showed atheroma regression at 8-month follow-up. Significant negative correlations were observed between percentage change in plaque volume and change in the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (r = -0.190, p = 0.05), docosahexaenoic acid (DHA)/AA ratio (r = -0.231, p = 0.02), and EPA+DHA/AA ratio (r = -0.240, p = 0.02). Furthermore, percentage change in the fibrous component volume was negatively and significantly correlated with change in the EPA/AA ratio (r = -0.206, p = 0.04) and EPA+DHA/AA ratio (r = -0.217, p = 0.03). Multivariate regression analysis showed that change in the EPA+DHA/AA ratio was a significant predictor of percentage change in plaque volume and fibrous component volume (β = -0.221, p = 0.02, and β = -0.200, p = 0.04, respectively). In conclusion, decreases in serum n-3 to n-6 polyunsaturated fatty acid ratios are associated with progression in coronary atherosclerosis evaluated using virtual histology intravascular ultrasound in statin-treated patients with coronary artery disease.

Topics: Aged; Biomarkers; Chromatography, Gas; Coronary Artery Disease; Coronary Vessels; Disease Progression; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pravastatin; Prospective Studies; Quinolines; Treatment Outcome; Ultrasonography, Interventional

A low n-3 to n-6 polyunsaturated fatty acids (PUFAs) ratio is reported to be associated with cardiovascular events. However, the effects of statins on this ratio have not been fully examined.. A total of 101 patients with coronary artery disease, who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of pravastatin. Serum PUFA levels were measured at baseline and 8 months after treatment with statins.. Pitavastatin was used to treat 51 patients and the remaining 50 patients were treated using pravastatin. A significant positive correlation was observed between the percent change in low-density lipoprotein cholesterol and that in dihomogamma-linolenic acid (r = .376, P = .007), arachidonic acid (AA; r = .316, P = .02), eicosapentaenoic acid (EPA; r = .408, P = .003), or docosahexaenoic acid (DHA; r = .270, P = .056) in the pitavastatin group. However, these correlations were not observed in the pravastatin group. The DHA/AA ratio decreased significantly in the pitavastatin group only (from 0.96 to 0.83, P = .0002) and the DHA/AA ratio was significantly lower in the pitavastatin group at 8 months (0.83 vs 0.96, P = .03). The EPA/AA ratio did not show significant changes in either group.. Pitavastatin decreased the serum DHA/AA ratio, whereas pravastatin had no effect on this ratio. Neither pitavastatin nor pravastatin had an effect on the serum EPA/AA ratio in patients with coronary artery disease.

Topics: Aged; alpha-Linolenic Acid; Arachidonic Acid; Cholesterol, LDL; Coronary Artery Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Longitudinal Studies; Male; Middle Aged; Pravastatin; Prospective Studies; Quinolines

Although statin-induced regression in coronary atherosclerosis seems to be greater in patients with acute coronary syndrome than in those with stable coronary artery disease, no reports have examined this. The purpose of the present study was to compare the changes in coronary atherosclerosis in patients with stable versus unstable angina pectoris (AP). The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound, and analyzable intravascular ultrasound data were obtained from 119 patients (83 patients with stable AP and 36 with unstable AP). A significant decrease in plaque volume was observed in patients with unstable AP (-2.2%, p = 0.02) but not in patients with stable AP. A significant increase in the necrotic-core component (0.30 mm(3)/mm, p = 0.009) was observed only in patients with unstable AP. Significant positive correlations were observed between the percentage of change in platelet-activating factor acetylhydrolase and the percentage of change in plaque volume (r = 0.346, p = 0.05) in patients with unstable AP. No significant correlations were observed in patients with stable AP. Multivariate regression analyses showed that a reduction in platelet-activating factor acetylhydrolase was associated with regression in coronary atherosclerosis, particularly of the fibrous component (β = 0.443, p = 0.003), in patients with unstable AP. In conclusion, regression of the coronary artery plaque volume was greater, although statin therapy did not halt the increases in plaque vulnerability, in patients with unstable AP compared to those with stable AP. A reduction in the serum platelet-activating factor acetylhydrolase level was associated with regression in coronary atherosclerosis, particularly the fibrous plaque volume, in patients with unstable AP.

Topics: Aged; Angina, Stable; Angina, Unstable; Biomarkers; Coronary Artery Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Lipids; Male; Plaque, Atherosclerotic; Pravastatin; Quinolines; Regression Analysis; Treatment Outcome; Ultrasonography, Interventional

Systemic therapy with statin has been shown to lower the risk of coronary events; however, the in vivo effects of statin therapy on plaque volume and composition are less understood.. We conducted a prospective, open-labeled, randomized, multicenter study in 11 centers in Japan. A total of 164 patients were randomized to receive either 4 mg/d of pitavastatin (intensive lipid-lowering therapy) or 20 mg/d of pravastatin (moderate lipid-lowering therapy). Analyzable intravascular ultrasound data were obtained for 119 patients at baseline and at 8-month follow-up. The primary end point was the difference of volume changes in each of the 4 main plaque components (fibrosis, fibrofatty, calcium, and necrosis), assessed by virtual histology intravascular ultrasound, between the 2 groups.. The mean low-density lipoprotein cholesterol level at follow-up was significantly lower in the pitavastatin than in the pravastatin group (74 vs 95 mg/dL, P < .0001). During the 8-month follow-up period, statin therapy reduced the absolute and relative amount of fibrofatty component (pitavastatin: from 1.09 to 0.81 mm(3)/mm, P = .001; pravastatin: from 1.05 to 0.83 mm(3)/mm, P = .0008) and increased in the amount of calcium (pitavastatin: from 0.42 to 0.55 mm(3)/mm, P < .0001; pravastatin: from 0.44 to 0.55 mm(3)/mm, P = .005), whereas volume changes in both plaque components were not statistically different between the 2 groups.. Both pitavastatin and pravastatin altered coronary artery plaque composition by significantly decreasing the fibrofatty plaque component and increasing the calcified plaque component.

Topics: Aged; Coronary Artery Disease; Coronary Vessels; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Treatment Outcome; Ultrasonography, Interventional

Renal dysfunction is an independent risk factor for cardiovascular events. However, little is known regarding the impacts of renal dysfunction on coronary atherosclerosis.. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the TRUTH study using virtual histology intravascular ultrasound in 164 patients with angina pectoris. We analyzed correlations between the estimated glomerular filtration rate (eGFR) and coronary atherosclerosis before and during statin therapy.. Baseline eGFR was 64.5 mL/min per 1.73 m(2) . Serum low-density lipoprotein cholesterol level decreased significantly from 132 to 85 mg/dL (-35%, P < 0.0001) after 8 months. Weak, but significant, negative correlations were observed between eGFR and external elastic membrane volume (r = -0.228, P = 0.01) and atheroma volume (r = -0.232, P = 0.01) at baseline. The eGFR was also negatively correlated with fibro-fatty volume (r = -0.254, P = 0.005) and fibrous volume (r = -0.241, P = 0.008) at baseline. Multivariate regression analyses showed that eGFR was a significant independent predictor associated with statin pre-treatment volume in fibro-fatty (β = -0.23, P = 0.01) and fibrous (β = -0.203, P = 0.02) components. Furthermore, eGFR was positively correlated with volume change in the fibro-fatty component during statin therapy (r = 0.215, P = 0.02).. Decreased eGFR is associated with expanding remodelling and a greater atheroma volume, particularly the fibro-fatty and fibrous volume before statin therapy in patients with normal to mild renal dysfunction. Reduction of fibro-fatty volume during statin therapy gradually accelerated with decreasing renal function.

Topics: Aged; Biomarkers; Coronary Artery Disease; Coronary Vessels; Dyslipidemias; Female; Fibrosis; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Kidney; Kidney Diseases; Lipids; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Pravastatin; Prospective Studies; Quinolines; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; 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

Oxidized LDL accelerates vascular endothelial damage and the progression of early arteriosclerosis, and is known as an independent risk factor for coronary artery disease. In this study, we administered pioglitazone and pitavastatin for 16 weeks to 18 patients who had type 2 diabetes complicated by dyslipidemia and then investigated the influence of these 2 drugs on MDA-LDL(i. e., oxidized LDL). As a result, a significant decrease of MDA-LDL was observed in both groups, but a significant decrease of the MDA-LDL/LDL-C ratio (an indicator of the extent of oxidation of LDL) was only observed in the pioglitazone group. Accordingly, it was demonstrated that pioglitazone improves oxidative stress, and the possibility was suggested that the MDA-LDL/LDL-C ratio is useful for the evaluation of oxidative stress in clinical practice.

Topics: Aged; Arteriosclerosis; Biomarkers; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Disease Progression; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Lipoproteins, LDL; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Pioglitazone; Quinolines; Risk Factors; Thiazolidinediones

Pitavastatin is a novel, potent, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. This study compared the long-term efficacy of pitavastatin and simvastatin in dyslipidemic patients at high risk of coronary heart disease.. A 44-week blinded extension study was conducted at 24 centers in five European countries for patients who had previously completed a 12-week randomized, double-blind core study in which they received pitavastatin 4 mg or simvastatin 40 mg once daily. Patients originally randomized to pitavastatin 4 mg continued at the same dose throughout the extension study (n = 121). In simvastatin-treated patients (n = 57), the dose was increased to 80 mg in five patients who had not attained the National Cholesterol Education Program (NCEP) target for low-density lipoprotein cholesterol (LDL-C) during the core study. Primary endpoints were the proportion of patients attaining the NCEP and European Atherosclerosis Society (EAS) LDL-C targets, and the NCEP target for non-high-density lipoprotein cholesterol (non-HDL-C) at weeks 16 and 44.. Of the 178 patients who entered the extension study, 156 patients (109 in the pitavastatin group, 47 in the simvastatin groups) completed the 44-week treatment period. At week 44, NCEP and EAS targets were attained by 81.7% and 84.2%, respectively, of pitavastatin-treated patients, and 75.4% and 73.7%, respectively, of simvastatin-treated patients. NCEP targets for non-HDL-C were achieved by 79.2% of pitavastatin-treated patients and 70.2% of simvastatin-treated patients. Both treatments were generally well tolerated, but pitavastatin 4 mg was associated with a numerically lower incidence of discontinuations due to treatment-emergent adverse events (5.8% vs. 10.5% of patients) and a lower rate of myalgia (4.1% vs. 12.3%) compared with simvastatin 40-80 mg.. Pitavastatin 4 mg provides long-term efficacy similar to that of simvastatin 40-80 mg. Further studies should ascertain whether trends suggesting that pitavastatin may exhibit a more favorable long-term tolerability profile are statistically significant.

Topics: Aged; Cholesterol, LDL; Coronary Artery Disease; Double-Blind Method; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Quinolines; Simvastatin

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

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

Few studies have serially monitored the change of coronary plaque after statin therapy using multiple plaque imaging modalities.. A prospective open-label trial was performed to assess coronary plaque regression and stabilization following 52 weeks of pitavastatin treatment (2 mg/day). Coronary segments that included the most diseased plaque of 90 patients determined on angioscopy were analyzed using intravascular ultrasound (IVUS). The yellow grade of each plaque of 46 patients who had matched angioscopy and IVUS data was evaluated on angioscopy. Low-density lipoprotein-cholesterol (LDL-C) was reduced 34.5% (145.0+/-24.0 mg/dl to 93.6+/-22.6 mg/dl, P<0.001), and high-density lipoprotein cholesterol increased 17.8% (44.9+/-11.1 mg/dl to 51.9+/-11.7 mg/dl, P<0.001). Yellow grade decreased (2.9+/-0.8 to 2.6+/-0.7, P=0.040) during 52 weeks. The reduction of yellow grade was not correlated with the LDL-C level at 52 weeks or its change. The change of yellow grade was inversely correlated with maximum yellow grade at baseline. Percent atheroma volume on IVUS did not change during 52 weeks, but its change for 52 weeks was significantly correlated with LDL-C level at 52 weeks (Spearman's rank correlation coefficient 0.312, P=0.035).. Fixed dose pitavastatin stabilized vulnerable coronary plaques by the reduction of yellow grade without significant reduction of plaque volume. The stabilization and regression of atherosclerotic plaques by statin may differ, but both nonetheless contribute to the reduction of cardiovascular events (UMIN Clinical Trials Registry UMIN000001107).

Topics: Aged; Angioscopy; Cholesterol, LDL; Coronary Artery Disease; Drug Monitoring; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Plaque, Atherosclerotic; Quinolines; 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

Many clinical trials have shown that 3-hydroxy-3-methylglutaryl-conenzyme A reductase inhibitors (statins) can significantly reduce the incidence of coronary artery disease in both primary and secondary prevention. A recent study showed that aggressive lipid-lowering therapy with statins could achieve regression of coronary artery plaque evaluated with gray-scale intravascular ultrasound (IVUS). However, the actual changes in coronary artery plaque composition produced by statin therapy have not been well delineated.. This study will be a prospective, open-label, randomized multicenter study of 160 patients with stable or unstable angina who have undergone percutaneous coronary intervention with Virtual Histology IVUS (VH-IVUS). Patients will be randomly assigned to either the pitavastatin or pravastatin group. After treatment for 24-40 weeks, VH-IVUS will be performed again in the same segment of the coronary artery. The primary endpoint will be quantitative changes in each of the 4 components measured by VH-IVUS.. The treatment with statin on atheroma regression evaluated by intravascular ultrasound with Virtual Histology (TRUTH) study will be the first multicenter study using VH-IVUS to evaluate the effects of statins on changes in coronary artery plaque composition and the findings will clarify the mechanisms of coronary artery plaque stabilization.

Topics: Atherosclerosis; Coronary Artery Disease; Coronary Vessels; Endpoint Determination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Pravastatin; Prospective Studies; Quinolines; Ultrasonography, Interventional; User-Computer Interface

Virtual histology intravascular ultrasound (VH-IVUS) is used to diagnose coronary plaques and evaluate statin therapy. However, in most cases, quantitative changes in plaques have been evaluated in the chronic stage. We evaluated the quantitative and qualitative early effects of 2 statins on coronary lesions using VH-IVUS.. Patients with acute coronary syndrome who underwent emergency percutaneous coronary intervention (PCI) were randomly assigned to receive pitavastatin (n=80; 2 mg/day) or atorvastatin (n=80; 10 mg/day) immediately after PCI. All patients underwent a blood lipid test and VH-IVUS evaluation of non-PCI lesions at admission and after 2-3 weeks of statin administration. After treatment, total cholesterol and low-density lipoprotein-cholesterol (LDL-C) showed significant decreases to similar levels in each group (P<0.001). In the pitavastatin group, the plaque volume index and fibrofatty volume index (FFVI) also decreased significantly. In patients from the pitavastatin group with a dense calcium ratio of < or =10% (n=61), the percentage changes in FFVI and LDL-C were correlated positively (r=0.305, P=0.017), whereas no significant changes were found after treatment in the atorvastatin group.. Fibrofatty composition and plaque volume decreased significantly following treatment with pitavastatin, which suggests that pitavastatin might have a higher affinity for fibrofat compared with atorvastatin.

Topics: Aged; Cholesterol; Cholesterol, LDL; Coronary Artery Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipids; Male; Middle Aged; Quinolines; Time Factors

Because postprandial hypertriglyceridemia and hyperglycemia may promote atherosclerosis, the present study investigated the effects of a clinical dose of pitavastatin on endothelial function and blood rheology in patients with coronary artery disease (CAD) before and after eating a test meal.. The 16 patients with stable CAD and mild dyslipidemia and 6 age-matched healthy men as controls were recruited. In each group, forearm blood flow (FBF) was measured during postischemic reactive hyperemia and blood samples were taken before and 2 h after the test meal. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also measured. The patients were started on pitavastatin 2 mg/day. The tests were repeated after 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in CAD patients than in control subjects (P=0.040). Fasting and postprandial FBF during reactive hyperemia significantly improved after pitavastatin treatment (P<0.05 vs baseline data for each phase) associated with reduced urine 8-OHdG, increased plasma adiponectin and improved lipid profile. No significant differences in baseline rheological parameters were seen between controls and CAD patients.. Pitavastatin significantly improved fasting and postprandial dyslipidemia and endothelial dysfunction in CAD patients, partly via reducing oxidative stress and increasing plasma adiponectin, although rheological parameters remained unchanged.

Topics: Adiponectin; Aged; Coronary Artery Disease; Dyslipidemias; Endothelium, Vascular; Fasting; Hemorheology; Humans; Male; Middle Aged; Oxidative Stress; Postprandial Period; Quinolines; Regional Blood Flow

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 compared short- and intermediate-term effects on lipid profiles, fibrinolytic parameter, and endothelial function between pitavastatin and atorvastatin. Short-term improvement of endothelial function was superior with pitavastatin compared to atorvastatin therapy. Pitavastatin could be a potentially better therapeutic choice for lipid-lowering and early alterations in endothelial function. Our study provides an important basis on which further trials involving larger numbers of patients may be studied prospectively.

Topics: Aged; Atorvastatin; Coronary Artery Disease; Endothelium, Vascular; Female; Fibrinolysis; Heptanoic Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Lipids; Male; Middle Aged; Prospective Studies; Pyrroles; Quinolines; Time Factors; Vasodilation

Topics: Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines

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

Topics: Cholesterol, LDL; Coronary Artery Disease; Humans; Quinolines

Topics: Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines; Simvastatin

Topics: Coronary Artery Disease; Humans; Japan; Quinolines

Topics: Cholesterol, LDL; Coronary Artery Disease; Humans; Japan; Quinolines

Topics: Coronary Artery Disease; Humans; Japan; Quinolines

Coronary high-intensity plaques detected by noncontrast T1-weighted imaging may represent plaque instability. High-intensity plaques can be quantitatively assessed by a plaque-to-myocardium signal-intensity ratio (PMR).. This pilot, hypothesis-generating study sought to investigate whether intensive statin therapy would lower PMR.. Prospective serial noncontrast T1-weighted magnetic resonance imaging and computed tomography angiography were performed in 48 patients with coronary artery disease at baseline and after 12 months of intensive pitavastatin treatment with a target low-density lipoprotein cholesterol level <80 mg/dl. The control group consisted of coronary artery disease patients not treated with statins that were matched by propensity scoring (n = 48). The primary endpoint was the 12-month change in PMR. Changes in computed tomography angiography parameters and high-sensitivity C-reactive protein levels were analyzed.. In the statin group, 12 months of statin therapy significantly improved low-density lipoprotein cholesterol levels (125 to 70 mg/dl; p < 0.001), PMR (1.38 to 1.11, an 18.9% reduction; p < 0.001), low-attenuation plaque volume, and the percentage of total atheroma volume on computed tomography. In the control group, the PMR increased significantly (from 1.22 to 1.49, a 19.2% increase; p < 0.001). Changes in PMR were correlated with changes in low-density lipoprotein cholesterol (r = 0.533; p < 0.001), high-sensitivity C-reactive protein (r = 0.347; p < 0.001), percentage of atheroma volume (r = 0.477; p < 0.001), and percentage of low-attenuation plaque volume (r = 0.416; p < 0.001).. Statin treatment significantly reduced the PMR of high-intensity plaques. Noncontrast T1-weighted magnetic resonance imaging could become a useful technique for repeated quantitative assessment of plaque composition. (Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technique [AQUAMARINE]; UMIN000003567).

Topics: Angiography; C-Reactive Protein; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Plaque, Atherosclerotic; Prospective Studies; Quinolines; Reproducibility of Results; Research Design; Tomography, X-Ray Computed; Treatment Outcome

The objective of the current study was to assess thin-capped fibroatheroma (TCFA) of the left main coronary artery (LMCA) and its changes after statin therapy.. We assessed the frequency and distribution of virtual histology intravascular ultrasound (VH-IVUS) thin-capped fibroatheroma (VH-TCFA) in the LMCA in 500 patients. Serial VH-IVUS examinations were available in 50 patients at 12-month follow-up.. The incidence of LM-TCFA was 8.8% (44/500). IVUS LMCA length was longer in patients with VH-TCFA vs without VH-TCFA. Reference external elastic membrane (EEM) area was similar, but reference lumen area and minimal lumen area were smaller in LMCA with VH-TCFA vs without VH-TCFA (P<.001). LMCA with VH-TCFA had a higher plaque burden (P<.001), a larger necrotic core area (P<.001), and more dense calcium (P<.001) at the maximum necrotic core (NC) site vs LMCA without VH-TCFA. In patients with an LMCA length greater than the median, 62% were located in the distal half of the LMCA. After 12 months of statin therapy, only 44.4% (4/9) of VH-TCFA had evolved to a non- VH-TCFA phenotype and 3 new VH-TCFA had appeared.. VH-TCFAs are clustered in the distal half of the LMCA with infrequent positive remodeling. It might persist despite the usual dose of statin therapy. Further study should confirm the changes in large vessels like the LMCA.

Topics: Aged; Atorvastatin; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Phenotype; Plaque, Atherosclerotic; Pyrroles; Quinolines; Registries; Retrospective Studies; Simvastatin; Ultrasonography, Interventional

It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function.. This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin.. This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration.. The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group.. The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.

Topics: Aged; Aged, 80 and over; Brachial Artery; Coronary Artery Disease; Endothelium, Vascular; Female; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Manometry; Microvessels; Middle Aged; Pyrimidines; Quinolines; Rosuvastatin Calcium; Sulfonamides

Topics: Adult; Anti-Infective Agents; Biomarkers; Coronary Angiography; Coronary Artery Disease; Electrocardiography; Fluorodeoxyglucose F18; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Multidetector Computed Tomography; Positron-Emission Tomography; Predictive Value of Tests; Quinolines; Treatment Outcome

The use of currently marketed drug-eluting stents presents safety concerns including increased late thrombosis, which is thought to result mainly from delayed endothelial healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). We recently developed a bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cationic electrodeposition technology. Statins are known to inhibit the proliferation of vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore hypothesized that statin-incorporated NP-eluting stents would attenuate in-stent stenosis without delayed endothelial healing effects.. Among six marketed statins, pitavastatin (Pitava) was found to have the most potent effects on VSMC proliferation and endothelial regeneration in vitro. We thus formulated a Pitava-NP-eluting stent (20µg Pitava per stent).. In a pig coronary artery model, Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as polymer-coated sirolimus-eluting stents (SES). At SES sites, delayed endothelial healing effects were noted, whereas no such effects were observed in Pitava-NP-eluting stent sites.. Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as SES without the delayed endothelial healing effects of SES in a porcine coronary artery model. This nanotechnology platform could be developed into a safer and more effective device in the future.

Topics: Animals; Blotting, Western; Cell Proliferation; Cells, Cultured; Constriction, Pathologic; Coronary Artery Disease; Disease Models, Animal; Drug-Eluting Stents; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Microscopy, Electron, Scanning; Nanoparticles; Quinolines; Swine

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

The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging.. Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics.. Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months.. Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant.. Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Plaque, Atherosclerotic; Quinolines; Tomography, Optical Coherence; Ultrasonography, Interventional

Topics: Coronary Artery Disease; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Plaque, Atherosclerotic; Quinolines; Tomography, Optical Coherence; Ultrasonography, Interventional

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

Recent lipid-lowering trials have reported that statin therapy may retard progression or stimulate regression of human coronary plaque. In the present study volumetric intravascular ultrasound (IVUS) analyses were performed to investigate the effect of pitavastatin, a newly developed statin, on regression of human coronary plaque.. Eighty-two patients matched for age and gender from 870 consecutive patients undergoing IVUS guided percutaneous coronary intervention were retrospectively assigned to either lipid-lowering therapy (n=41; pitavastatin 2 mg/day) or control group (n=41; diet only). Serial volumetric IVUS analyses of a matched left main coronary arterial site were performed. A significant reduction in low-density lipoprotein-cholesterol (LDL-C) level of 33.2% (p<0.001) was observed in the pitavastatin group. Plaque volume index (PVI) was significantly reduced in the pitavastatin group (10.6+/-9.4% decrease) compared with the control group (8.1+/-14.0% increase, p<0.001). There were positive correlations between the percent change in the PVI and follow-up LDL-C level (r=0.500, p<0.001) and the percent change in LDL-C level (r=0.479, p<0.001).. Lipid-lowering therapy with pitavastatin induced significant coronary plaque regression, associated with a significant reduction in the LDL-C level. The percent change in the PVI showed a significant positive correlation with the percent change in LDL-C level.

Topics: Aged; Angioplasty, Balloon, Coronary; Cholesterol, LDL; Coronary Artery Disease; Coronary Vessels; Data Interpretation, Statistical; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; Quinolines; Retrospective Studies; Triglycerides; Ultrasonography, Interventional