Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial.

BACKGROUND: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown. METHODS: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI. The primary end point was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year, which was powered for noninferiority of the OCT group compared with the IVUS group. Safety outcomes were also assessed. RESULTS: At 1 year, primary end point events occurred in 25 of 1005 patients (Kaplan-Meier estimate, 2.5%) in the OCT group and in 31 of 1003 patients (Kaplan-Meier estimate, 3.1%) in the IVUS group (absolute difference, -0.6 percentage points; upper boundary of one-sided 97.5% CI, 0.97 percentage points; P<0.001 for noninferiority). The incidence of contrast-induced nephropathy was similar (14 patients [1.4%] in the OCT group versus 15 patients [1.5%] in the IVUS group; P=0.85). The incidence of major procedural complications was lower in the OCT group than in the IVUS group (22 [2.2%] versus 37 [3.7%]; P=0.047), although imaging procedure-related complications were not observed. CONCLUSIONS: In patients with significant coronary artery lesions, OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year. The selected study population and lower-than-expected event rates should be considered in interpreting the trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique number: NCT03394079.

Comparison of optical coherence tomography-guided versus intravascular ultrasound-guided percutaneous coronary intervention: Rationale and design of a randomized, controlled OCTIVUS trial.

BACKGROUND: The clinical value of intracoronary imaging for percutaneous coronary intervention (PCI) guidance is well acknowledged. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most commonly used intravascular imaging to guide and optimize PCI in day-to-day practice. However, the comparative effectiveness of IVUS-guided versus OCT-guided PCI with respect to clinical end points remains unknown. METHODS AND DESIGN: The OCTIVUS study is a prospective, multicenter, open-label, parallel-arm, randomized trial comparing the effectiveness of 2 imaging-guided strategies in patients with stable angina or acute coronary syndromes undergoing PCI in Korea. A total of 2,000 patients are randomly assigned in a 1:1 ratio to either an OCT-guided PCI strategy or an IVUS-guided PCI strategy. The trial uses a pragmatic comparative effectiveness design with inclusion criteria designed to capture a broad range of real-world patients with diverse clinical and anatomical features. PCI optimization criteria are predefined using a common algorithm for online OCT or IVUS. The primary end point, which was tested for both noninferiority (margin, 3.1 percentage points for the risk difference) and superiority, is target-vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization) at 1 year. RESULTS: Up to the end of July 2020, approximately 1,200 "real-world" PCI patients have been randomly enrolled over 2 years. Enrollment is expected to be completed around the midterm of 2021, and primary results will be available by late 2022 or early 2023. CONCLUSION: This large-scale, multicenter, pragmatic-design clinical trial will provide valuable clinical evidence on the relative efficacy and safety of OCT-guided versus IVUS-guided PCI strategies in a broad population of patients undergoing PCI in the daily clinical practice.

Incidence and Clinical Significance of Poststent Optical Coherence Tomography Findings: One-Year Follow-Up Study From a Multicenter Registry.

BACKGROUND: Optical coherence tomography (OCT) was recently introduced to optimize percutaneous coronary intervention. However, the exact incidence and significance of poststent OCT findings are unknown. METHODS AND RESULTS: A total of 900 lesions treated with 1001 stents in 786 patients who had postprocedure OCT imaging were analyzed to evaluate the incidence of poststent OCT findings and to identify the OCT predictors for device-oriented clinical end points, including cardiac death, target vessel-related myocardial infarction, target lesion revascularization, and stent thrombosis. Patients were followed up to 1 year. Stent edge dissection was detected in 28.7% of lesions, and incomplete stent apposition was detected in 39.1% of lesions. The incidences of smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion were 92.9%, 61.0%, and 53.8%, respectively. Small minimal stent area, defined as a lesion with minimal stent area <5.0 mm(2) in a drug-eluting stent or <5.6 mm(2) in a bare metal stent, was observed in 40.4% of lesions. One-year device-oriented clinical end points occurred in 33 patients (4.5%). Following adjustment, irregular protrusion and small minimal stent area were independent OCT predictors of 1-year device-oriented clinical end points (P=0.003 and P=0.012, respectively). CONCLUSIONS: Abnormal poststent OCT findings were frequent. Irregular protrusion and small minimal stent area were independent predictors of 1-year device-oriented clinical end points, which were primarily driven by target lesion revascularization.

Comparison of near-infrared spectroscopy and optical coherence tomography for detection of lipid.

OBJECTIVES: To compare intracoronary near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) for the detection of lipid, to identify NIRS signals to differentiate superficial lipid, and to characterize the plaque with yellow block (YB) chemograms on NIRS. BACKGROUND: Intracoronary NIRS has been developed to detect lipid core plaque (LCP). METHODS: We investigated a total of 17 patients who underwent both OCT and NIRS. NIRS analysis included plaque lipid core burden index (LCBI), LCP length, and the presence of YB on the block chemogram. OCT analysis included maximum lipid arc (LA), the length of lipid (LL), lipid index, and the thinnest fibrous cap thickness (FCT). RESULTS: Twenty-five plaques with >40% plaque burden were analyzed. LCP, showing LCBI > 0, was observed in 20 plaques (80%) and YB was detected in seven plaques (28%). Plaque LCBI showed modest correlations with maximum LA and lipid index by OCT (r(2) = 0.319, P = 0.003 and r(2) = 0. 404, P = 0.001, respectively). Lipid length showed a significant correlation between NIRS and OCT measurements (r(2) = 0.581, P < 0.001). There was no significant difference in NIRS parameters between superficial and deep lipid. Plaques with YB compared with those without YB showed a larger LA, longer LL, and thinner FCT (185 ± 29° vs. 105 ± 76°, P = 0.014; 8.5 ± 3.3 mm vs. 3.3 ± 2.7 mm, P = 0.001; 112 ± 42 vs. 166 ± 61 µm, P = 0.033). CONCLUSIONS: NIRS and OCT parameters showed modest linear correlations in the measurement of lipid. The accurate depth of lipid in the vessel wall could not be identified by quantitative NIRS parameters. YB chemograms represented more vulnerable features on OCT.

Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study.

OBJECTIVE: Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction. APPROACH AND RESULTS: Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E' with improved strain parameters. No significant adverse effects of exenatide administration were detected. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.

BACKGROUND: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary artery lesions remains unclear. OBJECTIVES: This study compared the effectiveness and safety of OCT-guided vs IVUS-guided PCI for complex coronary artery lesions. METHODS: This was a prespecified, main subgroup analysis of complex coronary artery lesions in the OCTIVUS (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention) trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary endpoint was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: In 2,008 randomized patients, 1,475 (73.5%) underwent imaging-guided PCI for complex coronary artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) IVUS-guided PCI. At a median follow-up of 2.0 years, primary endpoint event had occurred in 47 patients (6.5%) in the OCT-guided group and in 56 patients (7.4%) in the IVUS-guided group (HR: 0.87; 95% CI: 0.59-1.29; P = 0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between the 2 groups (1.9% vs 1.5%; P = 0.46). The incidence of major procedural complications was lower in the OCT-guided group than in the IVUS-guided group (1.7% vs 3.4%; P = 0.03). CONCLUSIONS: Among patients with complex coronary artery lesions, OCT-guided PCI showed a similar risk of primary composite event of death from cardiac causes, target vessel-related myocardial infarction, or target vessel revascularization as compared with IVUS-guided PCI. (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention [OCTIVUS]; NCT03394079).

Randomized trial comparing the efficacy between different types of paclitaxel-eluting stents: the comparison of efficacy between COroflex PLEASe ANd Taxus stent (ECO-PLEASANT) randomized controlled trial.

AIMS: Paclitaxel-eluting stents (PESs) have been shown to inhibit neointimal hyperplasia after percutaneous coronary intervention. Coroflex Please (B Braun, Melsungen, Germany) is a newly developed PES. We compared the clinical and angiographic efficacy of Coroflex Please with Taxus Liberte (Boston Scientific, Natick, MA) in a real-world practice. METHODS AND RESULTS: We performed a prospective, open-label, randomized, controlled study that enrolled 945 patients undergoing percutaneous coronary interventions in 18 centers in Korea. The primary end point was clinically driven target vessel revascularization at 9 months. The baseline characteristics were mostly similar and comparable between 2 groups. At 9 months, the incidence of clinically driven target vessel revascularization was 14.6% for Coroflex and 6.4% for Taxus, which was significantly different (hazard ratio 2.43, 95% CI 1.50-3.94, noninferiority P value = 1.000). This is well corroborated by the difference of in-stent late loss between 2 stents (0.71 ± 0.64 mm vs 0.52 ± 0.50 mm, P < .001) by 9-month follow-up angiography (n = 415 vs 215). Among secondary clinical end points, stent thrombosis (definite and probable) for 1 year was 2.2% in Coroflex and 1.3% in Taxus (P = .317). Also, myocardial infarction for 9 months was higher in Coroflex group than that in Taxus (4.9% vs 1.6%, P = .012), which was partly contributed by the higher incidence of periprocedural myocardial infarction in Coroflex arm (2.2% vs 0.3%, P = .028). CONCLUSIONS: Coroflex Please was inferior to Taxus Liberte with regard to clinical and angiographic efficacy.

Preventive effects of exenatide on endothelial dysfunction induced by ischemia-reperfusion injury via KATP channels.

OBJECTIVE: The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by K(ATP) channel opening. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 µg) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001). CONCLUSIONS: The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR injury model.

Health-related quality-of-life after percutaneous coronary intervention in patients with UA/NSTEMI and STEMI: the Korean multicenter registry.

Compared with ST elevation myocardial infarction (STEMI), long-term outcomes are known to be worse in patients with unstable angina/non-STEMI (UA/NSTEMI), which might be related to the worse health status of patients with UA/STEMI. In patients with UA/NSTEMI and STEMI underwent percutaneous coronary intervention (PCI), angina-specific and general health-related quality-of-life (HRQOL) was investigated at baseline and at 30 days after PCI. Patients with UA/NSTEMI were older and had higher frequencies in female, diabetes and hypertension. After PCI, both angina-specific and general HRQOL scores were improved, but improvement was much more frequent in angina-related HRQOL of patients with UA/NSTEMI than those with STEMI (44.2% vs 36.8%, P < 0.001). Improvement was less common in general HRQOL. At 30-days after PCI, angina-specific HRQOL of the patients with UA/NSTEMI was comparable to those with STEMI (56.1 ± 18.6 vs 56.6 ± 18.7, P = 0.521), but general HRQOL was significantly lower (0.86 ± 0.21 vs 0.89 ± 0.17, P = 0.001) after adjusting baseline characteristics (P < 0.001). In conclusion, the general health status of those with UA/NSTEMI was not good even after optimal PCI. In addition to angina-specific therapy, comprehensive supportive care would be needed to improve the general health status of acute coronary syndrome survivors.

Polymorphisms of the Interferon gamma gene and coronary artery disease in the Korean population.

Abundant evidence supports the hypothesis that inflammation plays an important role in the development of coronary artery disease (CAD). In this study, we investigated whether genetic polymorphisms of the Interferon gamma (IFNG) gene were associated with the number of diseased vessels in CAD patients in the Korean population. To observe the association between the IFNG gene and the number of diseased vessels, we genotyped 635 CAD patients for a single nucleotide polymorphism (SNP, rs2430561) and a microsatellite (CA(n) repeats, rs3138557) located in the first intron of the IFNG gene using the direct sequencing and gene scan method. The number of microsatellites was increased in the one- and two-vessel disease groups. A combined analysis of the genotype of rs2430561 and the number of microsatellites revealed that the number of diseased vessels was associated with CA(12)-TT and CA(13)-TT. Our results suggest that the IFNG gene may be one of the factors determining the extent of CAD in the Korean population. Larger collaborative studies are needed to confirm these results.

Self-Monitoring of Blood Pressure and Feed-back Using APP in TReatment of UnconTrolled Hypertension (SMART-BP): A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Self-monitoring of blood pressure (SMBP) is a reliable method used to assess BP accurately. However, patients do not often know how to respond to the measured BP value. We developed a mobile application-based feed-back algorithm (SMBP-App) for tailored recommendations. In this study, we aim to evaluate whether SMBP-App is superior to SMBP alone in terms of BP reduction and drug adherence improvement in patients with hypertension. METHODS: Self-Monitoring of blood pressure and Feed-back using APP in TReatment of UnconTrolled Hypertension (SMART-BP) is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App compared with SMBP alone. Patients with uncomplicated essential hypertension will be randomly assigned to the SMBP-App (90 patients) and SMBP alone (90 patients) groups. In the SMBP group, the patients will perform home BP measurement and receive the standard care, whereas in the SMBP-App group, the patients will receive additional recommendations from the application in response to the obtained BP value. Follow-up visits will be scheduled at 12 and 24 weeks after randomization. The primary endpoint of the study is the mean home systolic BP. The secondary endpoints include the drug adherence, the home diastolic BP, home and office BP. CONCLUSIONS: SMART-BP is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App. If we can confirm its efficacy, SMBP-App may be scaled-up to improve the treatment of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04470284.

Clinical Results of Drug-Coated Balloon Treatment in a Large-Scale Multicenter Korean Registry Study.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficacy and safety of treatment with drug-coated balloon (DCB) in a large real-world population. METHODS: Patients treated with DCBs were included in a multicenter observational registry that enrolled patients from 18 hospitals in Korea between January 2009 and December 2017. The primary outcome was target lesion failure (TLF) defined as a composite of cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization at 12 months. RESULTS: The study included 2,509 patients with 2,666 DCB-treated coronary artery lesions (1,688 [63.3%] with in-stent restenosis [ISR] lesions vs. 978 [36.7%] with de novo lesions). The mean age with standard deviation was 65.7±11.3 years; 65.7% of the patients were men. At 12 months, the primary outcome, TLF, occurred in 179 (6.7%), 151 (8.9%), 28 (2.9%) patients among the total, ISR, and de novo lesion populations, respectively. A history of hypertension, diabetes, acute coronary syndrome, previous coronary artery bypass graft, reduced left ventricular ejection fraction, B2C lesion and ISR lesion were independent predictors of 12 months TLF in the overall study population. CONCLUSIONS: This large multicenter DCB registry study revealed the favorable clinical outcome of DCB treatment in real-world practice in patient with ISR lesion as well as small de novo coronary lesion.

Efficacy and Safety of SID142 in Patients With Peripheral Arterial Disease: A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Clinical Trial.

PURPOSE: Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. METHODS: This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. FINDINGS: In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n = 86) or the Renexin (n = 84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P = 0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P = 0.0171). IMPLICATIONS: SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. CLINICALTRIALS: gov identifier: NCT03318276.

Efficacy of coronary imaging on bifurcation intervention.

During the coronary bifurcation intervention procedure, imaging including intravascular ultrasound and optical coherence tomography is essential to provide precise anatomy of the lesion and morphological information. This consensus document between the Korean Bifurcation Club and the Japanese Bifurcation Club summarizes practical guidelines and current evidences on lesion assessment, device selection, procedural guidance, and the optimization of bifurcation intervention by the imaging.

Reduced Coronary Flow Reserve Is Associated with Impaired Ventricular-vascular Interaction in Patients with Obstructive Sleep Apnea.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with cardiac and arterial damage and adverse cardiovascular outcomes. We aimed to determine whether coronary flow reserve (CFR), which represents microvascular dysfunction, might be associated with the ventricular-vascular coupling index (VVI), which represents the afterload-adjusted contractility in patients with OSA. Methods: We enrolled 281 patients (257 males; mean age, 43±11 years) with newly diagnosed OSA. Transthoracic echocardiography was performed, and adenosine-associated CFR was measured in the left anterior descending coronary artery. We evaluated the differences between the patients with normal CFR ≥2.5 and reduced CFR <2.5. VVI was calculated using the effective arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees) as follows: 10×Ea/Ees. Results: The normal CFR group (n=214) showed increased Ees (7.28±2.31 vs. 8.14±2.33 mmHg/mL, p=0.016) and preserved VVI (3.17±1.53 vs. 2.78±1.20, p=0.044) compared with the reduced CFR group (n=67). There were no differences in LV dimension, LV ejection fraction, left atrial-volume index, E/e', left atrial strain and LV global longitudinal strain between the 2 groups (all p>0.05). CFR was significantly correlated to Ees (r=0.139; p=0.023) and VVI (r=-0.137; p=0.025). Conclusions: Reduced CFR is associated with decreased Ees and impaired VVI in OSA patients. It suggests the necessity of more intensive observation in OSA patients with reduced CFR to improve cardiovascular outcomes.

Neointima characteristics as a prognostic marker for drug-coated balloon angioplasty in patients with in-stent restenosis: an optical coherence tomography study.

BACKGROUND: Research has shown that the prognosis of in-stent restenosis (ISR) lesions after drug-coated balloon (DCB) angioplasty can differ in relation to in-stent neointimal characteristics. However, changes in neointima characteristics after DCB have not been studied. This study sought to investigate changes in neointima characteristics after DCB for ISR. METHODS: From the Yonsei Optical Coherence Tomography (OCT) registry, data on DCBs performed in patients with ISR were collected. Neointima characteristics were categorized as homogeneous, heterogeneous, layered neointima, and neoatherosclerosis in each OCT procedure. Homogeneous and layered neointima were classified as a favorable neointima, while heterogeneous neointima and neoatherosclerosis were classified as an unfavorable neointima. The data of 67 ISR patients were analyzed. RESULTS: The median duration between initial and follow-up OCT was 9.6 months. Patients with homogeneous and layered neointima on the initial OCT before DCB mostly appeared as homogeneous (66.7 and 68.2%, respectively) on the follow-up OCT, whereas most of the patients with heterogeneous neointima on the initial OCT remained unaltered (70%). Patients with unfavorable neointima at either the initial (P = 0.023) or the follow-up OCT (P = 0.037) had a worse major adverse cardiovascular event-free survival than the other patients. Patients who showed unfavorable neointima at both the initial and the follow-up OCT had the worst event-free survival (P = 0.038). CONCLUSIONS: The follow-up OCT neointimal characteristics after DCB for ISR was associated with initial OCT characteristics. Sustained unfavorable neointima in serial OCT imaging may reflect poor prognosis in patients with ISR treated with DCB.

S-amlodipine plus chlorthalidone vs. S-amlodipine plus telmisartan in hypertensive patients unresponsive to amlodipine monotherapy: study protocol for a randomized controlled trial.

BACKGROUND: The efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy. METHODS/DESIGN: This study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study. Hypertension patients who have been treated with amlodipine (5 mg) or S-amlodipine (2.5 mg) monotherapy for ≥2 weeks and whose mean diastolic blood pressure (DBP) is greater than 90 mmHg will be randomized to either S-amlodipine (2.5 mg) plus chlorthalidone (25 mg) or S-amlodipine (2.5 mg) plus telmisartan (40 mg) therapy. The primary efficacy endpoint is mean sitting DBP change after 12 weeks of treatment. The study objective is to prove the non-inferiority of the former combination (test drug) as compared to the latter one (control) with a non-inferiority margin of 3 mmHg in mean DBP change. The secondary endpoints are 6-week DBP change, 6- and 12-week sitting systolic BP (SBP) change, and the attainment of the target BP (SBP < 140 mmHg or DBP < 90 mmHg). Urine albumin, albumin/creatinine ratio (ACR), pulse wave velocity, central BP, 24-h ambulatory BP monitoring, and body fluid composition analysis will be performed at each hospital's discretion. The sample size was estimated as 170 in total with 1:1 randomization. DISCUSSION: This is the first study comparing the efficacy of a CCB plus chlorthalidone versus a CCB plus an ARB in patients who are not responding to CCB single therapy. The study result will help clinicians to choose between chlorthalidone and telmisartan in CCB-unresponsive patients. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03226340. Registered on 2 December 2015.

Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study.

PURPOSE: Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FINDINGS: A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, -16.1 [1.6] mm Hg vs -1.7 [2.2] mm Hg [P < 0.001] for MSSBP; -8.8 [1.0] mm Hg vs -1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (-49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. IMPLICATIONS: Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

Effects of intraluminal irradiation with Holmium-166 for TIPS stenosis: experimental study in a swine model.

OBJECTIVE: We wanted to evaluate the effectiveness of intraluminal irradiation with Holmium-166 ((166)Ho) for reducing the pseudointimal hyperplasia (PIH) in the transjugular intrahepatic portosystemic shunt (TIPS) tract in a swine model. MATERIALS AND METHODS: TIPS was performed in 12 domestic pigs, after the creation of portal hypertension by intraportal injection of a mixture of N-butyl-2-cyanoacrylate (NBCA) and lipiodol. Five pigs first underwent intraluminal irradiation (30 Gy) in the parenchymal tract with using a (166)Ho solution-filled balloon catheter, and this was followed by the placement of a nitinol stent in the TIPS tract. For the seven control pigs, the balloon was filled with saline and contrast media mixture. Two weeks later, follow-up portography and histological analysis were performed. RESULTS: TIPS was successfully performed in all twelve pigs with achieving artificially induced portal hypertension. Portography performed two weeks after TIPS showed the patent tracts in the TIPS tracts that were irradiated with (166)Ho (5/5, 100%), whereas either completely (5/6, 83.3%) or partially (1/6, 16.7%) occluded TIPS were seen in the seven pigs of the nonirradiated control group, except in one pig that experienced periprocedural death due to bleeding. Histological analysis showed a statistically significant difference for the maximal PIH (irradiated: 32.8%, nonirradiated: 76.0%, p < 0.001) between the two groups. CONCLUSION: Intraluminal irradiation with 30 Gy of (166)Ho for TIPS significantly improved the TIPS patency in a swine model of portal hypertension during a 2-week period of follow-up.

Clinical Significance of Lipid-Rich Plaque Detected by Optical Coherence Tomography: A 4-Year Follow-Up Study.

BACKGROUND: Lipid-rich plaque (LRP) is thought to be a precursor to cardiac events. However, its clinical significance in coronary arteries has never been systematically investigated. OBJECTIVES: This study investigated the prevalence and clinical significance of LRP in the nonculprit region of the target vessel in patients undergoing percutaneous coronary intervention (PCI). METHODS: The study included 1,474 patients from 20 sites across 6 countries undergoing PCI, who had optical coherence tomography (OCT) imaging of the target vessel. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, acute myocardial infarction, and ischemia-driven revascularization. Patients were followed for up to 4 years (median of 2 years). RESULTS: Lipid-rich plaque was detected in nonculprit regions of the target vessel in 33.6% of patients. The cumulative rate of nonculprit lesion-related MACE (NC-MACE) over 48 months in patients with LRP was higher than in those without LRP (7.2% vs. 2.6%, respectively; p = 0.033). Acute coronary syndrome at index presentation (risk ratio: 2.538; 95% confidence interval [CI]: 1.246 to 5.173; p = 0.010), interruption of statin use ≥1 year (risk ratio: 4.517; 95% CI: 1.923 to 10.610; p = 0.001), and LRP in nonculprit regions (risk ratio: 2.061; 95% CI: 1.050 to 4.044; p = 0.036) were independently associated with increased NC-MACE. Optical coherence tomography findings revealed that LRP in patients with NC-MACE had longer lipid lengths (p < 0.001), wider maximal lipid arcs (p = 0.023), and smaller minimal lumen areas (p = 0.003) than LRPs in patients without MACE. CONCLUSIONS: Presence of LRP in the nonculprit regions of the target vessel by OCT predicts increased risk for future NC-MACE, which is primarily driven by revascularization for recurrent ischemia. Lipid-rich plaque with longer lipid length, wider lipid arc, and higher degree of stenosis identified patients at higher risk of future cardiac events. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).