Percent Change In Plaque Volume Research Articles

Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome.

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)].

Effect of sitagliptin on plaque changes in coronary artery following acute coronary syndrome in diabetic patients: The ESPECIAL-ACS study

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS). MethodsThe ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis. ResultsA total of 41 patients were randomly allocated to either sitagliptin group (diet and exercise with sitagliptin 50–100mg daily, n=21) or control group (diet and exercise, n=20) within 72h after percutaneous coronary intervention, and underwent volumetric IVUS and IB-IVUS analyses at baseline and 6-month follow-up. At 6-month follow-up, the percent change in PV as primary endpoint was larger in the sitagliptin group than in the control group, but the difference was not statistically significant (−4.0±8.5% vs. −1.4±8.8%, p=0.35). In IB-IVUS analysis, the percent change in lipid PV significantly decreased in the sitagliptin group compared with the control group (−7.1±21.5% vs. 15.6±41.8%, p=0.03). ConclusionsCompared with diet and exercise therapy, sitagliptin did not significantly reduce coronary PV in diabetic patients with ACS at 6-month follow-up. However, the percent change in lipid PV significantly decreased in the sitagliptin group, suggesting that sitagliptin has a potential to stabilize the plaque vulnerability.

Comparison of the Effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque Determined by Angioscopy and Intravascular Ultrasound in Japanese With Stable Angina Pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] Randomized Trial)

Diminishing yellow color, evaluated by coronary angioscopy, is associated with plaque stabilization and regression. Our aim was to assess the effect of aggressive lipid-lowering therapy with rosuvastatin on plaque regression and instability. Thirty-seven patients with stable angina or silent myocardial ischemia who planned to undergo elective percutaneous coronary intervention and had angioscopic yellow plaques of grade 2 or more were randomized to high-dose (group H, 20 mg/day, n = 18) or low-dose (group L, 2.5 mg/day, n = 19) rosuvastatin therapy for 48 weeks. Yellow plaque was graded on a 4-point scale of 0 (white) to 3 (bright yellow) by angioscopy, and plaque volume was determined by intravascular ultrasound for plaques with a length of 5 to 15 mm. Color and volume were assessed at baseline and after 48 weeks by the investigators blinded to the rosuvastatin dosage, and were compared between the 2 dosing groups. The level of low-density lipoprotein-cholesterol decreased from 130.3 ± 25.5 mg/dl to 61.7 ± 16.5 mg/dl (-50 ± 19%: high intensity) in group H (p <0.001) and from 130.9 ± 28.5 mg/dl to 89.7 ± 29.0 mg/dl (-30 ± 22%: moderate intensity) in group L (mean ± SD, p <0.001). The average color grade of yellow plaques decreased from 2.0 to 1.5 in group H (p <0.001) and from 2.0 to 1.6 in group L (p <0.001) after 48 weeks. Plaque volume decreased significantly in group H but not in group L. The percent change in plaque volume was significantly larger in group H than in group L (p = 0.005). In conclusion, both high-dose and low-dose rosuvastatin increased plaque stability. However, high-dose rosuvastatin was more effective than low-dose rosuvastatin in inducing plaque volume regression. Clinical Trial Registration No: UMIN-CTR, UMIN000003276.

Combined Lipid Lowering by Ezetimibe and Statin and Coronary Plaque Regression: A Meta- Analysis of Randomized Controlled Trials

Background: It is not clear whether the addition of ezetimibe to statin will result in greater reduction in coronary plaque. We aimed to perform a meta-analysis of all RCTs and prospective studies that evaluated role of dual lipid lowering strategy in atherosclerosis regression. Methods: We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus and relevant references for RCTs (inception through December 20, 2015 without language restrictions) and performed meta-analysis using random effects model. Percentage change in plaque volume, change in lumen volume, percentage change in LDL, HDL and hsCRP were measured outcomes. Results: 3 RCTs and 1 prospective non randomized trial with a total population of 554 comprising mostly of Asian population were analyzed. Statin plus ezetimibe showed significantly greater lowering of plaque volume than statin alone (WMD -4.13 mm3 range of -7.42 mm3 to 0.85 mm3; p=0.01); there was a trend towards increased lumen volume in combination group without statistical significance [WMD 1.90 mm3 (-4.61 to 8.40); p=0.57).Combination strategy resulted in significantly higher percentage lowering of LDL at the end of follow up [WMD: -16.16(-22.47 to -9.85) p ≤ 0.00001]. No differences in percentage change in HDL and hsCRP were observed between two groups. Conclusion: Combination lipid lowering by statin plus ezetimibe causes significantly greater reduction in plaque volume and lowering of LDL cholesterol. Further larger studies are needed to validate the findings in all population groups.

Abstract 14134: Effects of Statin Plus Ezetimibe versus Statin Alone on Coronary Atherosclerosis in Acute Coronary Syndrome

Introduction: IMPROVE-IT trial showed that ezetimibe plus statin treatment, as compared with statin alone, decreased cardiovascular events in patients with acute coronary syndrome (ACS). However, proir studies have failed to show a beneficial effect of ezetimibe on carotid plaque progression when added to statin treatment. Hypothesis: The addition of ezetimibe to statin therapy affects coronary plaque behavior in the non-culprit vessel. Methods: We conducted a prospective, randomized open-label parallel group study with blind endpoint evaluation conducted at 10 centers in Japan. A total of 128 statin naïve patients with ACS undergoing intravascular ultrasound (IVUS) guided percutaneous coronary intervention were randomized and nonculprit coronary lesions associated with mild-to-moderate stenosis in 103 patients had evaluable IVUS examinations at baseline and at 8 to 12 months follow-up. Conventional IVUS and integrated backscatter (IB)-IVUS measurements at 1-mm intervals were calculated. Patients were randomly assigned to receive either 2mg/day of pitavastatin plus 10mg/day ezetimibe or 2mg/day of pitavastatin. Primary endpoints were the percentage change in non-culprit coronary plaque volume and percent change in lipid plaque volume. Results: Mean low density lipoprotein cholesterol was reduced from 125mg/dl to 65mg/dl in the combination therapy group receiving statin plus ezetimibe (n=50) and 126mg/dl to 87 mg/dl in the statin alone group (n=53)(between group difference of 16.9%, P&lt;0.0001). Length of analyzed segment did not differ between the groups (median 38.0 vs. 41.2 mm, p=0.40). The primary endpoint, percent change in plaque volume, was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups resulted in reduction of plaque volume compared with baseline (both p=0.001). The percent change in lipid plaque volume did not differ between the groups (4.3 vs. -3.0%, P=0.37). Conclusions: Among patients with acute coronary syndrome, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone.

Abstract 11806: Not Glycemic Control Using Sitagliptin But Lipid Control is Associated With Change in Coronary Atherosclerosis in Patients With Type 2 Diabetes -A Serial Integrated Backscatter Intravascular Ultrasound Study

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. However, clinical usefulness of DPP-4 inhibitors, particularly effects of these drugs on coronary atherosclerosis has not been fully evaluated. Hypothesis: We assessed the hypothesis that sitagliptin, a DPP-4 inhibitor, has beneficial effects on coronary atherosclerosis beyond its hypoglycemic action. Methods: A prospective, open-labeled, randomized multicenter study was performed at 6 Japanese centers. Twenty-eight patients with type 2 diabetes who have undergone elective percutaneous coronary intervention (PCI) were randomly assigned to either the sitagliptin group (group S) or control group (group C). Neither DPP-4 inhibitors nor glucagon-like peptide-1 analogues have been used in group C during study period. Non- PCI lesions were evaluated by integrated backscatter (IB)-intravascular ultrasound (IVUS) at the time of PCI and at 48-week follow-up. The primary end point was percentage change in plaque volume measured using grayscale IVUS and the secondary end point was changes in plaque compositions measured using IB-IVUS. Results: Grayscale IVUS analysis demonstrated that plaque volume tended to be decreased in both groups (group S: -1.7%; group C: -3.2%), but could not reach statistically significance. In addition, percentage changes in plaque volume did not differ between the 2 groups. On IB-IVUS analysis, a significant decrease in the lipid component (group S: from 200.1 to 179.8 mm3, p=0.02; group C: from 298.3 to 256.6 mm3, p=0.1) and an increase in the calcified component (group S: from 2.1 to 3.2 mm3, p=0.06; group C: from 2.3 to 4.8 mm3, p=0.04) were observed. Univariate and multivariate regression analyses showed that sitagliptin use did not correlate with a decrease in the lipid component, whereas percentage change in serum non high-density lipoprotein cholesterol (HDL-C) was an independent and significant predictor associated with change in the lipid component (β=0.454, p=0.04). Conclusions: Sitagliptin had no effects on coronary atherosclerosis in patients with type 2 diabetes. Not glycemic control but lipid control, particularly a decrease in non-HDL-C was associated with the reduction in lipid component.

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

Effects of Phase II Comprehensive Cardiac Rehabilitation on Coronary Plaque Volume After Acute Coronary Syndrome

The present study aimed to determine the effects of phase II (PII) comprehensive cardiac rehabilitation (CR) on coronary plaque volume in patients after acute coronary syndrome (ACS).We assigned 46 patients with ACS who had undergone standard phase I CR into groups who proceeded with PII-CR (PII-CR; n = 21) and those who did not (non-PII-CR; n = 25). We then measured anthropometric parameters and daily physical activity using a pedometer for up to 60 days. The isokinetic strength of the knee extensor and flexor muscles and exercise tolerance were tested and non-culprit lesions were analyzed using volumetric intravascular ultrasound at baseline and 6 months later.Baseline characteristics did not significantly differ between the two groups and exercise tolerance was significantly improved in both. Waist size and fat weight were significantly decreased, and muscle strength was significantly increased in the PII-CR group but not in the non-PII-CR group. The percent change in plaque volume (primary endpoint) did not differ significantly between the two groups. The percent change in plaque volume was significantly and negatively correlated with daily physical activity.Although risk factors, muscle strength, and exercise tolerance were improved by PII-CR, plaque regression did not differ significantly between the two study groups. A significant correlation between percent change in coronary plaque volume and physical activity was observed. A comprehensive phase II-CR, including frequent supervised exercise sessions and a program encouraging an increase in daily physical activity, may reduce plaque volume in patients after ACS (UMIN000006038).

Effect of combination of ezetimibe and a statin on coronary plaque regression in patients with acute coronary syndrome: ZEUS trial (eZEtimibe Ultrasound Study)

BackgroundMany trials have shown that statins can reduce plaque volume (PV) associated with the degree of LDL-C reduction.The goal of this study is to determine whether the combination of ezetimibe and a statin produces greater reductions in coronary plaque volume compared to statin monotherapy in patients with acute coronary syndrome (ACS). MethodsProspective serial intravascular ultrasound (IVUS) of non-culprit lesions of the target vessel was performed in 95 patients with ACS. Of these, 50 patients were administered combination of atorvastatin 20mg/day and ezetimibe 10mg/day. 45 subjects treated by atorvastatin 20mg/day alone were the control group. At the beginning and 24weeks after PCI, quantitative PV was accessed by IVUS. The primary end point was the percentage change in non-culprit coronary PV. ResultsLDL-C was significantly decreased by 49.8% in the ezetimibe/atorvastatin group compared with 34.6% in the atorvastatin group. Significant regression of plaque volume was observed from baseline to follow-up in both groups. The percentage changes in PV were greater in the ezetimibe/atorvastatin group than in the atorvastatin alone group (12.5% versus 7.6%, p=0.06), but statistically not significant. In 34 diabetic patients, regression of PV was significantly greater in the ezetimibe/atorvastatin group than in the statin alone group (13.9% versus 5.1%, p=0.04) and % change of PV significantly correlated with LDL-C reduction. ConclusionsAdditional LDL-C reduction with combination therapy tended to reduce more plaque regression compared to a statin alone in patients with ACS. In diabetic patients, further reduction of LDL-C was associated with a significantly greater reduction in PV.

Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in Japanese patients with stable coronary artery disease

Background: Recent clinical trials have demonstrated that intensive low-density lipoprotein-cholesterol (LDL-C) lowering therapy by strong statins could prevent recurrent cardiovascular event and have beneficial regressive effects on coronary plaques. Otherwise, the use of ezetimibe in combination with statin has been reported to provide greater reduction in LDL-C level than statin monotherapy. However, it is not established whether additional LDL-C lowering achieved with the addition of ezetimibe to statin monotherapy will lead to further reduction in coronary plaque volume. Methods: In this prospective, open-label, randomized study, 40 patients with stable coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI), whose LDL-C levels were higher than 100 mg/dl, were divided into combination therapy group (n=21, rosuvastatin 5mg plus ezetimibe 10mg daily) or statin monotherapy group (n=19, rosuvastatin 5mg daily). Serial volumetric intravascular ultrasound (IVUS) analysis were performed at baseline and after 6 months of follow-up for a non-PCI site. Results: LDL-C level was significantly decreased by 54.1% in the combination group (from 132.7±31.7 mg/dl to 59.5±17.1 mg/dl, p<0.001) vs. 42.1% in the monotherapy group (from 122.0±15.7 mg/dl to 69.1±19.7 mg/dl, p<0.001). Plaque volume (PV) was significantly reduced in the combination group (14.2±12.9% decrease) compared with the monotherapy group (2.1±17.0% decrease; p=0.016). Moreover, percent change in PV showed a significantly positive correlation with percent change and nominal change of LDL-C (r=0.403, p=0.011, and r=0.418, p=0.008, respectively), and percent change of non high-density lipoprotein cholesterol (r=0.380, p=0.024). It also showed a significant positive correlation with follow-up small dense LDL level (r=0.455, p=0.006). Conclusions: Aggressive LDL-C lowering therapy by ezetimibe in addition to statin may exert significant regression of coronary plaque volume compared with usual-dose statin monotherapy in patients with stable CAD.

No harmful effect of stem cell mobilization by granulocyte-colony stimulating factor on non-culprit coronary plaques after sirolimus-eluting stent implantation

Purpose: Previous studies have demonstrated that stem cell mobilization by granulocyte-colony stimulating factor (G-CSF) attenuates the endothelial dysfunction in mechanically disrupted animal artery models. However, some clinical studies have shown increased neointimal hyperplasia in patients who underwent bare metal stent implantation. Furthermore, the effect of stem cell mobilization on non-culprit plaques is unknown. The purpose of this study was to evaluate the effects of stem cell mobilization by G-CSF on non-culprit coronary plaques after sirolimus-eluting stent (SES) implantation. Methods: This double-blinded randomized placebo-control study (primarily designed to evaluate the effect of stem cell mobilization by G-CSF on endothelial function after SES implantation) assigned patients to the G-CSF group (n=50) or the placebo group (n=50). After successful SES implantation, the patients received subcutaneous injection of G-CSF (300 mg daily) or saline for 5 days. Follow-up angiography and intravascular ultrasound (IVUS) was performed 9 months after SES implantation. Plaque volume was measured by IVUS at non-culprit segments which were defined as more than 5mm proximal or distal from the stent. Percent change in plaque volume (ΔPV) of non-culprit segments between post-procedure and follow-up was evaluated. Results: Plasma CD34+ cell level did not differ between the 2 groups at baseline (0.94±0.55 vs. 0.93±0.68/μL, p = 0.96). It significantly increased after G-CSF injection (0.94±0.55 vs. 18.39±13.55/μL, p <0.001) but did not in the placebo group (0.93±0.68/μL vs. 1.35±2.36/μL, p = 0.22). No death or myocardial infarction was observed during follow-up. Follow-up IVUS was available in 39 G-CSF patients (78%) and 43 placebo patients (86%) (p = 0.30). There was no significant difference in ΔPV between both groups at proximal (-11.0±16.4% vs. -14.7±9.8%, p = 0.35) and distal (-5.1±28.6% vs. -4.9±17.3%, p = 0.97) non-culprit segments. Conclusion: Stem cell mobilization by G-CSF does not increase plaque volume at non-culprit coronary plaques after SES implantation.

Impacts of age on coronary atherosclerosis and vascular response to statin therapy

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm(3)/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm(3)/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (-2.4 %, p = 0.007) and plaque volume (-3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (β = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.

Comparison of Effects of Serum n-3 to n-6 Polyunsaturated Fatty Acid Ratios on Coronary Atherosclerosis in Patients Treated With Pitavastatin or Pravastatin Undergoing Percutaneous Coronary Intervention

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.

Effects of Serum n-3 to n-6 Polyunsaturated Fatty Acids Ratios on Coronary Atherosclerosis in Statin-Treated Patients With Coronary Artery Disease

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.

Reverse Vessel Remodeling But Not Coronary Plaque Regression Could Predict Future Cardiovascular Events in ACS Patients With Intensive Statin Therapy

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.

Clustering of Metabolic Syndrome Components Attenuates Coronary Plaque Regression During Intensive Statin Therapy in Patients With Acute Coronary Syndrome

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.

New evidence on pitavastatin: efficacy and safety in clinical studies

Importance of the field: Many clinical trials of pitavastatin have been done since its launch. New insights on pitavastatin from these trials are summarized and evaluated.Areas covered in this review: The results of clinical studies using pitavastatin, from 2008 to 2009, the LIVES study, the JAPAN-ACS study, the CHIBA study, the PIAT study and Phase III clinical trials in the West are reviewed.What the reader will gain: In the LIVES study, pitavastatin showed significant and continuous elevation of high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), as well as potential decrease in low-density lipoprotein cholesterol (LDL-C), in addition to long-term safety. Non-inferiority of pitavastatin against atorvastatin in the percentage change in plaque volume was proved in the JAPAN-ACS study. Also, comparable effects on LDL-C reduction rate of pitavastatin versus atorvastatin were confirmed in the CHIBA study and Phase III clinical trials in the West, and a greater increase in HDL-C was observed than with atorvastatin in the PIAT study.Take home message: Pitavastatin is a useful potent statin in raising HDL-C as well as in lowering of LDL-C, though a large-scale, clinical trial to confirm prevention of cardiovascular events is needed in the future.

Effect of Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome: A Multicenter Randomized Trial Evaluated by Volumetric Intravascular Ultrasound Using Pitavastatin Versus Atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] Study)

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).

A randomized placebo-controlled study on the effect of nifedipine on coronary endothelial function and plaque formation in patients with coronary artery disease: the ENCORE II study.

AimsEndothelial dysfunction and plaque formation are features of atherosclerosis. Inhibition of L-type calcium channels or HMG-CoA pathway improves endothelial function and reduces plaque size. Thus, we investigated in stable coronary artery disease (CAD) the effects of a calcium antagonist on coronary endothelial function and plaque size.Methods and resultsIn 454 patients undergoing PCI, acetylcholine (10−6 to 10−4 M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30–60 mg/day and followed for 18–24 months.Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns.ConclusionThe ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.

Abstract 2015: Effect of Early Intensive Statin Therapy on Regression of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome: The Multi-Center Randomized Trial Evaluated by Volumetric Intravascular Ultrasound Comparing Pitavastatin versus Atorvastatin (JAPAN-ACS study)

A prior single center study reported that early lipid-lowering therapy with atorvastatin 20 mg/day in patients (pts) with acute coronary syndrome (ACS) significantly reduced coronary plaque volume (PV) of the non-culprit site by intravascular ultrasound (IVUS) evaluation. Effect of statins other than atorvastatin on PV has not been evaluated yet in the setting of ACS. A prospective, randomized open-label parallel group study with blinded endpoint evaluation was perfomed at 33 centers in Japan. Pts with ACS undergoing IVUS-guided percutaneous coronary intervention (PCI) were randomly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin within 72 hours after PCI. The primary endpoint was the percentage change in non-culprit coronary PV by IVUS from baseline to 8 –12 months follow-up. The study was powered to evaluate non-inferiority of pitavastatin to atorvastatin. Between November 2005 and October 2006, 307 pts (pitavastatin group 153 pts and atorvastatin group 154 pts) were enrolled; 252 pts (82%) had IVUS image qualified for evaluation both at baseline and at follow-up. Low-density lipoprotein cholesterol (LDL-C) decreased from 130.9±33.3mg/dL at baseline to 81.1±23.4mg/dL at 8 –12 months follow-up (p= 0.001) in the pitavastatin group and from 133.8±31.4mg/dL to 84.1±27.4mg/dL (p= 0.001) in the atorvastatin group. PV decreased from 49.8±28.8mm 3 to 41.6±25.0mm 3 (p= 0.001) in the pitavastatin group and from 63.9±33.9mm 3 to 53.3±31.7mm 3 (p= 0.001) in the atorvastatin group. Mean percentage change in PV was −16.9±13.9% and −18.1±14.2% (p=0.5) in the pitavastatin and atorvastatin group, respectively. Upper limit of the 95% confidence interval of the mean difference in percentage change in PV between the two groups (1.11% (−2.27 to 4.48)) did not exceed the pre-defined non-inferiority margin of 5%. There was no significant correlation between percent change in plaque volume and LDL-C at baseline or at follow-up. Early intensive statin therapy with 4mg/day of pitavastatin or 20mg/day of atorvastatin in Japanese patients with ACS resulted in remarkable regression of coronary PV. The effect of pitavastatin 4mg/day on coronary PV was similar to that of atorvastatin 20mg/day.