Population-Based Study of the Incidence and Mortality Rate of Acute Aortic Dissection.

BACKGROUND: Acute aortic dissection (AAD) has high morbidity and a high fatality rate for a cardiovascular disease. Recent studies suggested that the incidence of AAD is increasing. However, the actual incidence and mortality rates of AAD are not well known. This study investigated the current epidemiology of AAD within the Yatsushiro medical jurisdictional area.Methods and Results: A population-based review of patients with AAD was performed in a geographically well-defined area. Data were collected retrospectively from January 2011 to December 2020 for a total of 196 patients with AAD (Stanford Type A, n=126 [64.3%]; Stanford Type B, n=70 [35.7%]). The mean patient age was 74.3 years, and 55.6% (109/196) were women. The crude and age-standardized incidence rates of AAD in our medical jurisdictional area were 13.6 and 11.4 per 100,000 inhabitants per year, respectively. The crude and age-standardized 30-day mortality rates of AAD were 4.9 and 4.0 per 100,000 inhabitants per year, respectively. There were upward tendencies for both the incidence and 30-day mortality rate of AAD with age, with both being significantly higher in patients aged ≥85 years (P<0.001). CONCLUSIONS: This population-based study detected a higher incidence of AAD than previous studies, but reported a lower incidence of AAD in men than in women. Increasing age was associated with an increased incidence and mortality rate of AAD.

Pseudoaneurysm of mitral-aortic intervalvular fibrosa with rupture: a case report.

BACKGROUND: Mitral-aortic intervalvular fibrosa (MAIVF) is a fibrous region connecting the anterior mitral leaflet (AML) and aortic valve. Pseudoaneurysm of the MAIVF is a rare condition that has been reported as a sequela of infective endocarditis (IE) and surgical trauma. Here, we report a case of a ruptured pseudoaneurysm of the MAIVF, along with some literature reviews. CASE PRESENTATION: A 65-year-old man diagnosed with moderate aortic regurgitation five years previously had a fever of unknown origin. He suddenly developed headache and apraxia and was transported to our hospital. He was diagnosed with intracranial hemorrhage and admitted. One week after admission, echocardiography revealed aorto-mitral discontinuity and protrusion with severe regurgitant flow from left ventricular outflow tract to the left atrium. The AML was suspected to have ruptured. However, intraoperatively, the AML structure was preserved. A ruptured pseudoaneurysm of the MAIVF was also observed. Therefore, we successfully performed pseudoaneurysm repair using a bovine pericardial patch, aortic valve replacement, and mitral annuloplasty. CONCLUSIONS: P-MAIVF is a rare but potentially life-threatening complication of IE, for which timely diagnosis and prompt appropriate therapeutic intervention are required. In the present case, although neither obvious active IE nor history of previous IE could be identified, healed IE was considered based on the clinical course. The patient had intracranial hemorrhage (ICH) with well-controlled heart failure and underwent elective surgical repair more than one month after the onset of ICH, while the clinical course after the surgical procedure was uneventful.

Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Dose-Dependent Inhibitory Effect of Rosuvastatin in Japanese Patients with Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases-INVITATION Trial.

AIM: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. METHODS: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. RESULTS: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. CONCLUSIONS: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

Temporal trends in coronary intervention strategies and the impact on one-year clinical events: data from a Japanese multi-center real-world cohort study.

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used.

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

AIM: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. METHODS: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL. RESULTS: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008). CONCLUSIONS: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Imaging-guided PCI for event suppression in Japanese acute coronary syndrome patients: community-based observational cohort registry.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR ( http://www.umin.ac.jp/ctr/ ). Identifier: KICS (UMIN000015397).

Area-Based Medicine in the Super-Ageing Society in Japan.

Japan's health insurance system has reached a critical turning point owing to a decreasing birthrate, increasing longevity, and changes in disease trends. The Japanese government is promoting the establishment of a community-based integrated care system aimed at maintaining the dignity of elderly individuals and supporting independent living. This care system will ensure medical and nursing care, preventive measures, and independent living support. This type of care system should be based on the characteristics of individual geographical areas, as there are marked regional variations in patterns of aging, lifestyle, and the adequacy of local medical care. Therefore, it is important that medical services are tailored to fit the kind of medical care needed by residents of each geographical area and to provide medical services accordingly. In this paper, we propose a need for area-based medicine, whereby medical care is provided according to the characteristics of individual geographical areas in super-ageing societies such as that of Japan. J. Med. Invest. 67 : 40-43, February, 2020.

Importance of measurement of the diameter of the distal radial artery in a distal radial approach from the anatomical snuffbox before coronary catheterization.

Coronary catheterization by a distal radial approach at the site of the anatomical snuffbox has recently been reported to be both safe and useful. No data are available on the diameter of the distal radial artery (DRA) in Japan, and it is unclear whether the DRA is large enough to withstand the insertion of a conventional sheath by a traditional radial approach. We enrolled 142 patients who underwent coronary catheterization and evaluated the vessel diameter of the DRA using ultrasound. The vessel diameter of the DRA in the anatomical snuffbox (2.6 ± 0.5 mm) was significantly smaller than that of the proximal radial artery (PRA) at the conventional puncture site (3.1 ± 0.4 mm). The difference in vessel diameter between the DRA and PRA was 0.5 ± 0.4 mm, and the DRA/PRA ratio was 0.8 ± 0.1. Although the vessel diameter of the DRA was positively correlated with that of the PRA (r = 0.66, p < 0.0001), in some cases the DRA was extremely small compared to the PRA. When the vessel diameter of the DRA is smaller than the outer diameter of the sheath scheduled for use, we should puncture the PRA at the outset. We could perform coronary catheterization by a distal radial approach without major bleeding or adverse events, and there was no radial artery occlusion at the site of the anatomical snuffbox or the forearm. For coronary catheterization by a distal radial approach, we should evaluate whether there is sufficient vessel diameter using ultrasound before the procedure. In addition, this approach can be an effective option from the viewpoint of radial artery preservation.

Acute myocardial infarction following sequential multi-vessel occlusion in a case of polycythemia vera.

A 59-year-old female was brought to our emergency room with severe chest pain. Based on the electrocardiogram (ECG) and echocardiography, an acute coronary syndrome (ACS) was suspected. Her initial ECG showed ST elevation in the inferior leads (II, III, and aVF), which had progressed to involve the anterior leads (V2-V4) by the time she was shifted to the catheterization room. A coronary angiogram revealed total occlusion of the mid-left anterior descending (LAD) artery and a filling defect of the distal right coronary artery. Although we had emergently treated her using thrombus aspiration following stent implantation, lots of thrombi re-formed on the stent. We surmised her ACS was primarily caused by thrombus formation due to polycythemia vera (PV) based on the presence of increased blood consistency on admission. We performed repetitive long-inflation using a perfusion balloon and repeated thrombus aspiration. Finally, she was diagnosed as an untreated case of PV as a result of detailed blood investigations. Thereafter, we successfully treated her using the combination of dual antiplatelet therapy and direct oral anticoagulant therapy. Our experience highlights the importance of an urgent identification of PV. Effective management strategies should be successfully implemented in such patients as soon as possible. .

Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial.

BACKGROUND: Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD. METHODS: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol < 70 mg/dL). Serial volumetric IVUS findings obtained at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients were compared stratified by the presence or absence of CKD. RESULTS: CKD was observed in 52 patients (26%) among 202 enrolled patients. Compared with the non-CKD group, the CKD group was significantly older (71.5 ±â€¯8.6 years vs. 64.4 ±â€¯9.6 years, P < 0.001) with similar prevalence of comorbid coronary risk factors and lipid profiles. Similar to the non-CKD group (-1.4 [-2.8 to -0.1]% vs. -0.2 [-1.7 to 1.0]%, P = 0.002), the atorvastatin/ezetimibe combination significantly reduced ∆PAV compared with atorvastatin alone even in the CKD group (-2.6 [-5.6 to -0.4]% vs. -0.9 [-2.4 to 0.2]%, P = 0.04). CONCLUSIONS: As with non-CKD, intensive lipid-lowering therapy with atorvastatin/ezetimibe demonstrated stronger coronary plaque regression effect even in patients with CKD compared with atorvastatin monotherapy. TRIAL REGISTRATION: NCT01043380 (ClinicalTrials.gov).

Dose-dependent INhibitory effect of rosuVastatin In Japanese patienTs with Acute myocardial infarcTION on serum concentration of matrix metalloproteinases - INVITATION trial.

BACKGROUND: Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid-rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a critical role in inflammatory processes underlying plaque rupture. Some reports suggested statins inhibit the increased MMP levels after AMI. However, there are a few comparison studies between the different dosages of the same statin and circulating levels of MMPs. PURPOSE: This study will preliminarily investigate the potential effects of appropriate or low dose of rosuvastatin on circulating MMPs levels in AMI patients. Moreover, we will also obtain plasma from patients while undergoing diagnostic angiography to determine differences in various cardiac sites and peripheral vessels. METHODS: This study is a multicenter, open-label, randomized, parallel-group study to be conducted to compare the appropriate or low dose of rosuvastatin in the effect on serum levels of inflammatory markers in AMI patients. The eligible patients undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive either appropriate or low-dose rosuvastatin daily using a web-based randomization software within 24h after PCI. The low-dose group will be treated with rosuvastatin 2.5mg once daily with a follow-up. The appropriate-dose group will begin treatment with rosuvastatin 5mg once daily, and the dose of rosuvastatin will be titrated to 10mg within 4 weeks. During administration of the study treatment, subjects will undergo laboratory testing including MMPs and be monitored for the occurrence of adverse events up to 24 weeks. The primary endpoint will be the change rate of MMPs at 24 weeks after administration. CONCLUSIONS: INVITATION will compare the appropriate or low dose of rosuvastatin in the effects on serum levels of inflammatory markers including MMPs in AMI patients. This study will provide significant information on rosuvastatin as an anti-inflammatory agent for AMI.

Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto: Atrial Fibrillation Suppression Trial (SILK study).

BACKGROUND: Experimental studies suggest that angiotensin II-receptor blockers can influence atrial remodeling and may prevent atrial fibrillation (AF). Therefore, we hypothesized that irbesartan may prevent the recurrence of AF following either catheter ablation or electrical cardioversion of AF. METHODS: Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto (SILK study) is a prospective, multicenter, randomized, and open-label comparative evaluation of the effects of irbesartan and amlodipine on AF recurrence in hypertensive patients with AF who are scheduled to undergo catheter ablation or electrical cardioversion of AF. The primary end point was either AF or atrial tachycardia (AT) recurrence. AF/AT recurrence was evaluated for 6 months using 24-h Holter electrocardiogram and portable electrocardiogram. The secondary endpoints included the change in blood pressure, the interval from the procedure to the first AF/AT recurrence, cardiovascular events, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), and changes in the biomarkers [brain natriuretic polypeptide (BNP), high-sensitivity C-reactive protein (hs-CRP), urinary albumin/creatinine]. RESULTS: The study enrolled 98 patients (irbesartan; n=47, amlodipine; n=51). The recurrence of AF/AT was observed in 8 patients (17.0%) in the irbesartan group and in 10 patients (19.6%) in the amlodipine group. There was no significant difference in the AF/AT recurrence between the irbesartan and amlodipine groups. Blood pressure decreased similarly in both groups. There were no significant differences between the two groups as regards to the interval from the procedure to the first AF/AT recurrence, occurrence of cardiovascular events, changes in LAD and LVEF. BNP and urinary albumin/creatinine significantly decreased similarly in both groups, but no significant difference was found in hs-CRP between the two groups. CONCLUSIONS: In hypertensive patients with AF, treatment with irbesartan did not have any advantage over amlodipine in the reduction of AF/AT recurrence after catheter ablation or electrical cardioversion.

Prognostic Value of the CHADS2 Score for Adverse Cardiovascular Events in Coronary Artery Disease Patients Without Atrial Fibrillation-A Multi-Center Observational Cohort Study.

BACKGROUND: The CHADS2 score has mainly been used to predict the likelihood of cerebrovascular accidents in patients with atrial fibrillation. However, increasing attention is being paid to this scoring system for risk stratification of patients with coronary artery disease. We investigated the value of the CHADS2 score in predicting cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation. METHODS AND RESULTS: This was a multicenter, observational cohort study. The subjects had been admitted to one of the participating institutions with coronary artery disease requiring percutaneous coronary intervention. We calculated the CHADS2 scores for 7082 patients (mean age, 69.7 years; males, 71.9%) without clinical evidence of atrial fibrillation. Subjects were subdivided into low- (0-1), intermediate- (2-3), and high-score (4-6) groups and followed for 1 year. The end point was a composite of cardiovascular/cerebrovascular death, nonfatal myocardial infarction, and ischemic stroke at 1-year follow-up. Rates of triple-vessel/left main trunk disease correlated positively with CHADS2 score categories. CHADS2 scores among single, double, and triple-vessel/left main trunk groups were 2 (1-2), 2 (1-3), and 2 (2-3), respectively (P<0.001). A total of 194 patients (2.8%) had a cardiovascular/cerebrovascular event, and Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular/cerebrovascular events in proportion to a higher CHADS2 score (log-rank test, P<0.001). Multivariate Cox hazard analysis identified CHADS2 score (per 1 point) as an independent predictor of cardiovascular/cerebrovascular events (hazard ratio, 1.31; 95% CI, 1.17-1.47; P<0.001). CONCLUSIONS: This large cohort study indicated that the CHADS2 score is useful for the prediction of cardiovascular/cerebrovascular events in coronary artery disease patients without atrial fibrillation.

Clinical outcomes of percutaneous coronary intervention for acute coronary syndrome between hospitals with and without onsite cardiac surgery backup.

BACKGROUND: Based on the 2011 American College of Cardiology/American Heart Association percutaneous coronary intervention (PCI) guideline, it is recommended that PCI should be performed at hospital with onsite cardiac surgery. But, data suggest that there is no significant difference in clinical outcomes following primary or elective PCI between the two groups. We examined the impact of with or without onsite cardiac surgery on clinical outcomes following PCI for acute coronary syndrome (ACS). METHODS AND RESULTS: From August 2008 to March 2011, subjects (n=3241) were enrolled from the Kumamoto Intervention Conference Study (KICS). Patients were assigned to two groups treated in hospitals with (n=2764) or without (n=477) onsite cardiac surgery. Clinical events were followed up for 12 months. Primary endpoint was in-hospital death, cardiovascular death, myocardial infarction, and stroke. And we monitored in-hospital events, non-cardiovascular deaths, bleeding complications, revascularizations, and emergent coronary artery bypass grafting (CABG). There was no overall significant difference in primary endpoint between hospitals with and without onsite cardiac surgery [ACS, 7.6% vs. 8.0%, p=0.737; ST-segment elevation myocardial infarction (STEMI), 10.4% vs. 7.5%, p=0.200]. There was also no significant difference when events in primary endpoint were considered separately. In other events, revascularization was more frequently seen in hospitals with onsite surgery (ACS, 20.0% vs. 13.0%, p<0.001; STEMI, 21.9% vs. 14.5%, p=0.009). We performed propensity score matching analysis to correct for the disparate patient numbers between the two groups, and there was also no significant difference for primary endpoint (ACS, 8.6% vs. 7.5%, p=0.547; STEMI, 11.2% vs. 7.5%, p=0.210). CONCLUSIONS: There is no significant difference in clinical outcomes following PCI for ACS between hospitals with and without onsite cardiac surgery backup in Japan.

Lipid profile associated with coronary plaque regression in patients with acute coronary syndrome: Subanalysis of PRECISE-IVUS trial.

BACKGROUND AND AIMS: Although dual low-density lipoprotein cholesterol (LDL-C)-lowering therapy (DLLT) with statin-ezetimibe combination showed clinical benefit in patients with acute coronary syndrome (ACS) confirming "the lower, the better," the underlying mechanisms of DLLT are still unknown. METHODS: PRECISE-IVUS trial evaluated the effects of DLLT on IVUS-derived coronary atherosclerosis and lipid profile, compared with atorvastatin monotherapy, quantifying the coronary plaque response in 100 ACS patients. We explored the potential predictors of plaque regression. RESULTS: Lower total cholesterol, LDL-C, triglyceride, remnant-like particles cholesterol, and stronger reduction of small dense LDL-C and cholesterol absorption markers were observed in patients with plaque regression compared to those with progression. Multivariate analysis revealed that achieved LDL-C was the strongest predictor for coronary plaque regression (95% CI: 0.944-1.000, p = 0.05), followed by age (95% CI: 0.994-1.096, p = 0.09). CONCLUSIONS: Incremental LDL-C lowering by DLLT was associated with stronger coronary plaque regression, reconfirming that lowering LDL-C to levels below previous targets provided additional clinical benefit.

Synergistic effect of ezetimibe addition on coronary atheroma regression in patients with prior statin therapy: Subanalysis of PRECISE-IVUS trial.

BACKGROUND: The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment. METHODS: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70 mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment. RESULTS: The baseline low-density lipoprotein cholesterol level (100.7 ± 23.1 mg/dl vs. 116.4 ± 25.9 mg/dl, p < 0.001) and lathosterol (55 (38 to 87)) µg/100 mg total cholesterol vs. 97 (57 to 149) µg/100 mg total cholesterol, p < 0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p < 0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-1.3 (-3.1 to -0.1)% vs. -0.9 (-2.3 to 0.9)%, p = 0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (-1.8 (-3.6 to -0.3)% vs. -0.1 (-1.6 to 0.8)%, p = 0.002). CONCLUSION: Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.

Impact of candesartan on cardiovascular events after drug-eluting stent implantation in patients with coronary artery disease: The 4C trial.

OBJECTIVE: The purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). BACKGROUND: Candesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events. METHODS: The 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386). RESULTS: The incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p=0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p=0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p=0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p=0.0493). CONCLUSIONS: The 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years.

Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention: The Multicenter Randomized Controlled PRECISE-IVUS Trial.

BACKGROUND: Despite standard statin therapy, a majority of patients retain a high "residual risk" of cardiovascular events. OBJECTIVES: The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI). METHODS: This trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients. RESULTS: The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (-1.538%; 95% confidence interval [CI]: -3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (-1.4%; 95% CI: -3.4% to -0.1% vs. -0.3%; 95% CI: -1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. CONCLUSIONS: Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition-induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380).