Impact of Age on Antiplatelet Monotherapy in the Chronic Maintenance Period After Percutaneous Coronary Intervention: A Post Hoc Analysis From the HOST-EXAM Extended Study.

BACKGROUNDS: The HOST-EXAM Extended study reported the benefit of clopidogrel monotherapy over aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). This age-specific subgroup analysis of the study aimed to assess the impact of age on antiplatelet monotherapy after PCI. METHODS: We analysed data from the per-protocol population (4717 patients) with a median follow-up of 5.8 years. The old age group comprised 2033 patients (43.1%), defined as those 65 years of age or older. The primary end point was the composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. The secondary end points were thrombotic composite outcomes and any bleeding. RESULTS: Age correlated with an elevated risk of adverse events, particularly from age 65. Clopidogrel monotherapy was associated with a reduction of the primary end point in both the old age group (19.4% vs 23.1%, hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.664-0.968; P = 0.022) and the young age group (7.8% vs 11.7%, HR 0.646, 95% CI 0.506-0.825; P < 0.001), without significant interaction (interaction P = 0.167). These findings were consistent for the secondary composite thrombotic end point and any bleeding events (interaction P value of secondary thrombotic end point: 0.786; interaction P value of any bleeding end point: 0.565). Consistent results were observed in analyses with a 75-year age cutoff and in subgroup analyses by 10-year age intervals. CONCLUSIONS: In patients requiring antiplatelet monotherapy after PCI, occurrence of both ischemic and bleeding events dramatically increased from age 65. The beneficial impact of clopidogrel over aspirin monotherapy was consistent regardless of age. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02044250.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Comparative effects of nebivolol and carvedilol on left ventricular diastolic function in older patients with heart failure and preserved ejection fraction.

Background: Although many studies have compared carvedilol and nebivolol in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), such comparative studies for the elderly have not been reported yet. Nebivolol is known to be effective for improving diastolic function of elderly patients with HF. Thus, this study aimed to determine whether nebivolol could improve LV diastolic function to a greater extent than carvedilol in older patients aged over 70 years. Methods: This trial was a prospective, randomized, open-label, single-center, active-controlled study that enrolled 62 patients with class II or III HF over 70 years of age with an LVEF ≥40%. Patients were randomized into a carvedilol group or a nebivolol group. Transthoracic echocardiography was performed at baseline and 12 months by the same investigator who was blinded to clinical data. The primary endpoint was E/e' measured by echocardiographic evaluation 12 months after treatment. Results: The median duration of follow-up was 24 months. Baseline clinical characteristics and echocardiographic parameters, such as LV diastolic function indices, did not differ significantly between carvedilol and nebivolol groups. Twelve-month follow-up echocardiography data showed no significant difference in E/e' or other LV diastolic function indices between the two groups. There were no significant changes in echocardiographic parameters over 12 months in either group. Conclusions: There was no difference between carvedilol and nebivolol for improving diastolic function of elderly HF patients with LVEF ≥40%. This study showed no superiority of nebivolol over carvedilol in elderly patients with HF.

Complete chloroplast genome sequence of Solanum iopetalum, one of the tuber-bearing wild potato relatives.

Solanum iopetalum belongs to the Solanaceae family and is one of the tuber-bearing wild Solanum species. In this study, chloroplast genome sequencing of the species, completed with Illumina sequencing technology, is presented. The length of the chloroplast genome is 155,625 bp with a GC content of 37.86%. It comprises a large single copy (LSC) region of 86,057 bp, a small single copy (SSC) region of 18,382 bp, and two inverted repeat regions (IRa and IRb) of 25,593 bp. Additionally, 158 functional genes in the genome are identified, including 105 protein-coding genes, 8 ribosomal RNAs, and 45 transfer RNAs. Phylogenetic analysis revealed that S. iopetalum is grouped into a large clade with other Solanum species, including cultivated potatoes (S. tuberosum) and is closely related to Mexican Solanum species (S. stoloniferum, S. verrucosum, S. hougasii, S. hjertingii, and S. demissum). This study provides useful genomic information for future breeding and evolutionary studies of S. iopetalum and other Solanum species.

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia.

PURPOSE: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. METHODS: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. IMPLICATIONS: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. CLINICALTRIALS: gov identifier: NCT04584736.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

The Busan Regional CardioCerebroVascular Center Project's Experience Over a Decade in the Treatment of ST-segment Elevation Myocardial Infarction.

OBJECTIVES: The Regional CardioCerebroVascular Center (RCCVC) project was initiated to improve clinical outcomes for patients with acute myocardial infarction or stroke in non-capital areas of Korea. The purpose of this study was to evaluate the outcomes and issues identified by the Busan RCCVC project in the treatment of ST-segment elevation myocardial infarction (STEMI). METHODS: Among the patients who were registered in the Korean Registry of Acute Myocardial Infarction for the RCCVC project between 2007 and 2019, those who underwent percutaneous coronary intervention (PCI) for STEMI at the Busan RCCVC were selected, and their medical data were compared with a historical cohort. RESULTS: In total, 1161 patients were selected for the analysis. Ten years after the implementation of the Busan RCCVC project, the median door-to-balloon time was reduced from 86 (interquartile range [IQR], 64-116) to 54 (IQR, 44-61) minutes, and the median symptom-to-balloon time was reduced from 256 (IQR, 180-407) to 189 (IQR, 118-305) minutes (p<0.001). Inversely, the false-positive PCI team activation rate increased from 0.6% to 21.4% (p<0.001). However, the 1-year cardiovascular death and major adverse cardiac event rates did not change. Even after 10 years, approximately 75% of the patients had a symptom-to-balloon time over 120 minutes, and approximately 50% of the patients underwent inter-hospital transfer for primary PCI. CONCLUSIONS: A decade after the implementation of the Busan RCCVC project, although time parameters for early reperfusion therapy for STEMI improved, at the cost of an increased false-positive PCI team activation rate, survival outcomes were unchanged.

Complete chloroplast genome sequence of Solanum hjertingii, one of the wild potato relatives.

Solanum hjertingii is a wild tuber-bearing species classified in the Solanaceae family. The chloroplast genome of S. hjertingii was completed via de novo assembly using Illumina paired-end sequencing data. Total length of the chloroplast genome of S. hjertingii is 155,545 bp consisting of 85,976 bp in a large single copy, 18,383 bp in a small single copy, and 25,593 bp in a pair of inverted repeat regions. Its structure is circular and typically quadripartite. It contains 158 predicted genes in total, including 105 protein-coding, 45 tRNA, and eight rRNA genes. Maximum likelihood phylogenetic analysis of the sequence along with 33 species in the Solanaceae family revealed that S. hjertingii belongs to a large clade with other Solanum species including S. tuberosum and is most closely grouped in the clade with S. hougasii and S. stoloniferum in the clade.

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

BACKGROUND: Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population. METHODS: We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250. FINDINGS: Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035). INTERPRETATION: Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. FUNDING: ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

Complete chloroplast genome sequence of the wild diploid potato relative, Solanum acaule.

Solanum acaule is a wild tuber-bearing species classified in the Solanaceae. The complete chloroplast genome of S. acaule was constructed by de novo assembly using Illumina paired-end (PE) sequencing data. The chloroplast genome of S. acaule is circular and has a length of 155,570 bp and typical quadripartite consisting of 86,020 bp of large single copy, 18,364 bp of small single copy, and 25,593 bp of a pair of inverted repeat regions. A total of 158 genes were annotated including 105 protein-coding genes, 45 tRNA genes, and eight rRNA genes. Maximum likelihood phylogenetic analysis of the sequence with 31 species in the Solanaceae revealed that S. acaule is fully resolved in a large clade with nine other Solanum species including S. tuberosum.

Prognostic effect of increased left ventricular wall thickness in severe aortic stenosis.

BACKGROUND: It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS. METHODS AND RESULTS: This study included 290 severe AS patients (mean age 69.4 ± 11.0 years; 136 females) between January 2008 and December 2018. For outcome assessment, the endpoint was defined as death from all causes, cardiovascular death, and the aortic valve replacement (AVR) surgery rate. During follow-up (48.7 ± 39.0 months), 157 patients had AVR, 43 patients died, and 28 patients died from cardiovascular causes. Patients with increased LVWT underwent AVR surgery much more than those without LVWT (60.0% vs. 39.0%, p < 0.001). Furthermore, in patients with increased LVWT, the all-cause and cardiovascular death rates were significantly lower in the AVR group than in the non-AVR group (8.8% vs. 27.3%, p < 0.001, 4.8%, vs. 21.0%, p < 0.001). Multivariate analysis revealed that increased LVWT, age, dyspnea, and AVR surgery were significantly correlated with cardiovascular death. CONCLUSIONS: In patients with severe AS, increased LVWT was associated with a higher AVR surgery rate and an increased rate of cardiovascular death independent of other well-known prognostic variates. Thus, these findings suggest that increased LVWT might be used as a potential prognostic factor in severe AS patients.

Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.

PURPOSE: Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). METHODS: In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. FINDINGS: Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). IMPLICATIONS: The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

Efficacy and Tolerability of Pitavastatin Versus Pitavastatin/Fenofibrate in High-risk Korean Patients with Mixed Dyslipidemia: A Multicenter, Randomized, Double-blinded, Parallel, Therapeutic Confirmatory Clinical Trial.

PURPOSE: Dyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD. METHODS: This multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150-500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non-HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment. FINDINGS: The difference in the mean percentage change in non-HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was -12.45% (95% CI, -17.18 to -7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non-HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. IMPLICATIONS: In these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non-HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.

Community-Based Pre-Hospital Electrocardiogram Transmission Program for Reducing Systemic Time Delay in Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: In acute ST-segment elevation myocardial infarction (STEMI), on-site transmission of electrocardiogram (ECG) has been shown to reduce systemic time delay to reperfusion and improve outcomes. However, it has not been adopted in community-based emergency transport system in Korea. METHODS: Busan Regional Cardio-cerebrovascular Center and Busan Metropolitan City Fire and Safety Headquarters (BMFSH) jointly developed and conducted a pre-hospital ECG transmission program. Seven tertiary hospitals and 22 safety stations of BMFSH participated. Systemic time delay to reperfusion of STEMI patients in the program was compared with that of 95 patients transported by 119 emergency medical system (EMS) before the program was implemented. RESULTS: During the study period, 289 ECG transmissions were made by 119 EMS personnel, executed within 5 minutes in 88.1% of cases. Of these, 42 ECGs were interpreted as ST-segment elevation. Final diagnosis of STEMI was made in 20 patients who underwent primary percutaneous coronary intervention. With the program, systemic time delay to reperfusion was significantly reduced (median [interquartile range; IQR], 76.0 [62.2-98.7] vs. 90.0 [75.0-112.0], p<0.01). Significant reduction of door-to-balloon time was also observed (median [IQR], 45.0 [34.0-69.5] vs. 58.0 [51.0-68.0], p=0.03). The proportion of patients with systemic time delay shorter than 90 minutes rose (51.6% vs. 75.0%, p=0.08) with pre-hospital ECG transmission. CONCLUSIONS: We developed and implemented a community-based pre-hospital ECG transmission program for expeditious triage of STEMI patients. Significant reductions of systemic time delay and door-to-balloon time were observed. The expanded use of pre-hospital ECG transmission should be encouraged to realize the full potential of this program.

Long-Term Outcomes of Unprotected Left Main Coronary Artery Disease: Comparison of Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention.

OBJECTIVE: We compared the long-term outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease in a real-world population. BACKGROUND: CABG is the standard of care for ULMCA disease. Contemporary randomized trials have reported conflicting results with the two revascularization strategies for the treatment of ULMCA disease at intermediate-term follow-up. METHODS: We evaluated 422 consecutive patients with ULMCA disease who underwent CABG (n = 273) or PCI (n = 149) from 1998-2008. The primary outcome measure was major adverse cardiac and cerebrovascular event (MACCE) rate, defined as the composite of all-cause death, myocardial infarction (MI), stroke, or target-vessel revascularization (TVR) at 10 years. Propensity-score matched (PSM) analysis was used to assess long-term MACCE. RESULTS: The cumulative 10-year incidence of risk for MACCE was not significantly different between the PCI and CABG groups (24.8% vs 20.5%, respectively; log rank P=.22; log rank PSM P=.45). The risk for all-cause death was not significantly different between the two groups (log rank P=.09; PSM log rank P=.51). The risk for stroke was significantly lower with PCI (log rank P=.02), but was not significant after matching (PSM log rank P=.27). The risk for TVR was significantly higher with PCI vs CABG prior to and after matching (log rank P<.001; log rank PSM P=.01). There were no significant differences in MACCE between the two groups when stratified by SYNTAX scores ≤22% (log rank P=.61) and >23% (log rank P=.06). CONCLUSION: In patients with ULMCA disease, PCI was comparable with CABG for long-term MACCE and death rates. The TVR rate was higher in the PCI group.

The complete chloroplast genome sequence of the Alstroemeria hybrid variety 'Hanhera'.

Alstroemeria, a member of the Alstroemeriaceae family, is a species from South America. The chloroplast genome of Alstroemeria spp. was completed by de novo assembly using a small amount of whole genome sequencing data. The chloroplast genome of Alstroemeria spp. was 155,672 bp in length consisting of 84,379 bp of large single copy, 17,815 bp of small single copy, and 26,739 bp of a pair of inverted repeat regions. A total of 157 genes were annotated including 103 protein-coding genes (PCGs), 46 tRNA genes, and eight rRNA genes. Maximum likelihood phylogenetic analysis with seven species belonging to the Alstroemeriaceae or Liliaceae family revealed that Alstroemeria spp. is grouped with the species in the Alstroemeriaceae family.

Chloroplast genome sequence of the hybrid variety 'Gagsi', one of the colored calla lilies (Zantedeschia spp.).

The complete chloroplast genome of Zantedeschia spp. in the family Araceae was constituted by de novo assembly using a small amount of whole genome sequencing data. The chloroplast genome of Zantedeschia spp. was the circular DNA molecule with a length of 175,448 bp and consisted of 90,244 bp of large single copy, 8334 bp of small single copy, and 38,435 bp of a pair of inverted repeat regions. A total of 163 genes were annotated including 109 protein-coding genes, 46 tRNA genes and eight rRNA genes. Maximum likelihood phylogenetic analysis with 16 Araceae species revealed that Zantedeschia spp. is expectedly grouped with other Zantedeschia species.

Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy.

PURPOSE: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy. METHODS: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups. FINDINGS: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074). IMPLICATIONS: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.

Comparison of the Effects of Ticagrelor and Clopidogrel on Microvascular Dysfunction in Patients With Acute Coronary Syndrome Using Invasive Physiologic Indices.

BACKGROUND: Ticagrelor reduced the rate of myocardial infarction and death compared with clopidogrel in patients with acute coronary syndrome. However, little is understood about chronic treatment of ticagrelor on microvascular dysfunction. The objective of this study was to assess the impact of ticagrelor maintenance treatment on microvascular system and coronary flow in comparison with clopidogrel. METHODS: This study was a nonblinded, open-label, parallel-group, prospective, randomized controlled trial that enrolled 120 patients with acute coronary syndrome requiring stent implantation. Patients were randomized into the ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter) group. The primary end point was coronary microvascular dysfunction as measured by an index of microcirculatory resistance (IMR) at 6 months after treatment. RESULTS: The baseline clinical characteristics and physiological parameters, such as fractional flow reserve, coronary flow reserve, and IMR, did not differ between the ticagrelor and clopidogrel groups. Six-month follow-up physiological data showed that the IMR value was significantly lower in the ticagrelor group than the clopidogrel group (15.57±5.65 versus 21.15±8.39, P<0.01), and coronary flow reserve was higher in the ticagrelor group than in the clopidogrel group (3.85±0.72 versus 3.37±0.76, P<0.01). However, there was no difference in fractional flow reserve (0.87±0.08 versus 0.87±0.09, P=0.94) between the 2 groups. The improvement in IMR after 6 months of treatment was higher in the ticagrelor group (P<0.01). Analyses of 223 nonculprit vessels of registered patients based on physiological results showed no differences in baseline fractional flow reserve (0.93±0.13 versus 0.92±0.09, P=0.58), coronary flow reserve (3.62±1.27 versus 3.51±1.24, P=0.16), or IMR (21.37±12.37 versus 24.19±21.08, P=0.22) or in follow-up fractional flow reserve (0.91±0.09 versus 0.91±0.08, P=0.67), coronary flow reserve (3.91±1.22 versus 3.75±1.16, P=0.36), or IMR (19.43±10.32 versus 21.52±18.90, P=0.34) between the 2 groups. CONCLUSIONS: Compared with clopidogrel, 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome patients with stent implantation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02618733.

Effectiveness and Safety of Zotarolimus-Eluting Stent (Resolute™ Integrity) in Patients with Diffuse Long Coronary Artery Disease.

BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS: Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.