Identification of subgroups within a Japanese older adult population for whom statin therapy is effective in reducing mortality.

Use of statins for primary prevention can reduce all-cause mortality in Asian elderly populations, but their effect and the specific effective subgroups in the elderly Japanese population remain unclear. This study examined the relationship between statin therapy for primary prevention and mortality reduction in older Japanese adults, and investigated the effective subgroups. The cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33-0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group compared with that in the control group was 0.05 (95% CI, 0.04-0.06), and the number needed to treat was 21.20 (95% CI, 18.10-24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to <85 years and in patients with comorbidities such as diabetes, or dementia.

Use of the Shizuoka Hip Fracture Prognostic Score (SHiPS) to Predict Long-Term Mortality in Patients With Hip Fracture in Japan: A Cohort Study Using the Shizuoka Kokuho Database.

Hip fractures are common in patients of advanced age and are associated with excess mortality. Rapid and accurate prediction of the prognosis using information that can be easily obtained before surgery would be advantageous to clinical management. We performed a population-based retrospective cohort study using an 8.5-year Japanese claims database (April 2012-September 2020) to develop and validate a predictive model for long-term mortality after hip fracture. The study included 43,529 patients (34,499 [79.3%] women) aged ≥65 years with first-onset hip fracture. During the observation period, 43% of the patients died. Cox regression analysis identified the following prognostic predictors: sex, age, fracture site, nursing care certification, and several comorbidities (any malignancy, renal disease, congestive heart failure, chronic pulmonary disease, liver disease, metastatic solid tumor, and deficiency anemia). We then developed a scoring system called the Shizuoka Hip Fracture Prognostic Score (SHiPS); this system was established by scoring based on each hazard ratio and classifying the degree of mortality risk into four categories based on decision tree analysis. The area under the receiver operating characteristic (ROC) curve (AUC) (95% confidence interval [CI]) of 1-year, 3-year, and 5-year mortality based on the SHiPS was 0.718 (95% CI, 0.706-0.729), 0.736 (95% CI, 0.728-0.745), and 0.758 (95% CI, 0.747-0.769), respectively, indicating good predictive performance of the SHiPS for as long as 5 years after fracture onset. Even when the SHiPS was individually applied to patients with or without surgery after fracture, the prediction performance by the AUC was >0.7. These results indicate that the SHiPS can predict long-term mortality using preoperative information regardless of whether surgery is performed after hip fracture.

Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population.

BACKGROUND: Although tranexamic acid (TXA) has occasionally been used to prevent postoperative recurrence of chronic subdural hematoma (CSDH) after burr hole craniotomy (BC), robust evidence of its efficacy has been lacking. OBJECTIVE: To assess the efficacy and safety of postoperative oral administration of TXA after BC for CSDH among the elderly. METHODS: This retrospective, propensity score-matched cohort study was carried out with a large Japanese local population-based longitudinal cohort in the Shizuoka Kokuho Database between April 2012 and September 2020. Patients included were age 60 years or older and had undergone BC for CSDH but were not undergoing dialysis. Covariates were collected from records of the preceding 12 months from the month of first BC, and patients were followed up for 6 months after surgery. The primary outcome was repeat surgery, and the secondary outcome was death or the onset of thrombosis. Data on postoperative TXA administration were collected and compared with controls using propensity score matching. RESULTS: Of the 8544 patients who underwent BC for CSDH, 6647 were included, with 473 placed in the TXA group and 6174 placed in the control group. After 1:1 matching, repeated BC was found to have been performed in 30 of 465 patients (6.5%) in the TXA group and in 78 of 465 patients (16.8%) in the control group (relative risk, 0.38; 95% CI, 0.26-0.56). No significant difference was observed for death or the onset of thrombosis. CONCLUSION: Oral administration of TXA reduced the occurrence of repeat surgery after BC for CSDH.

Effect of Functional Electrical Stimulation in Convalescent Stroke Patients: A Multicenter, Randomized Controlled Trial.

BACKGROUND: We evaluated whether the Walkaide® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20-85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. MATERIALS AND METHODS: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. RESULTS: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: -8.26 to 29.98, p = 0.26), respectively. CONCLUSIONS: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604.

Phase II study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE).

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive cancer for which effective systemic therapy has long been sought. Here, we assessed the efficacy and safety of lenvatinib in patients with unresectable ATC. PATIENTS AND METHODS: The study was investigator-initiated and conducted under a multicenter, open-label, nonrandomized, phase II design. Eligibility criteria included pathologically proven ATC; unresectable measurable lesion as defined by RECIST 1.1; age 20 years or older; ECOG PS 0-2; and adequate organ function. The primary end-point was overall survival. Secondary end-points were progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety. RESULTS: Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis, and 50 patients were included for safety analysis. The estimated 1-year overall survival rate was 11.9% (95% CI, 4.4%-23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an objective response rate of 11.9%, disease control rate of 73.8%, and clinical benefit rate of 33.3%. Adverse events of any grade were observed in 45 patients (90.0%), the most common of which of any grade included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and palmar-plantar erythrodysesthesia syndrome (26.0%). CONCLUSION: Lenvatinib treatment resulted in disappointing survival for unresectable ATC patients. Although the number of responders was small, responses were durable, indicating that lenvatinib may be beneficial for selected patients. Further investigation to identify suitable candidates for lenvatinib monotherapy is needed.

Statin Exposure and Pancreatic Cancer Incidence: A Japanese Regional Population-Based Cohort Study, the Shizuoka Study.

Preclinical studies suggest that statins contribute to the prevention of pancreatic cancer; however, the results of epidemiologic studies are inconsistent. Furthermore, sufficient data are unavailable for the general population of Asia. Here, we conducted an observational study using a comprehensive patient-linked, longitudinal health insurance database comprising the records of 2,230,848 individuals residing in Shizuoka Prefecture, Japan, from April 2012 to September 2018. We included individuals older than 40 years with data for medical examinations and statin exposure (≥365 statin prescription days). To balance baseline characteristics between the statin exposure and statin nonexposure groups, we used inverse probability of treatment propensity score weighting method. We estimated hazard ratios for associations with pancreatic cancer using the Cox proportional hazards regression model. Among 2,230,848 individuals, we included 100,537 in the statin exposure group (24%) and 326,033 in the statin nonexposure group (76%). Among the statin exposure group (352,485 person-years) and the statin nonexposure group (1,098,463 person-years), 394 (1.12 per 1,000 person-years) and 1176 (1.07 per 1,000 person-years) developed pancreatic cancer, respectively (P = 0.464). After adjustments using inverse probability of treatment weighting, the statin exposure group was associated with a decreased incidence of pancreatic cancer (hazard ratio, 0.84; 95% confidence intervals, 0.72-0.99; P = 0.036). In conclusion, the current Japanese regional population-based cohort study shows that statin exposure was associated with a lower incidence of pancreatic cancer. PREVENTION RELEVANCE: This study may support the possible role of statins in preventing pancreatic cancer in the general population in Japan.

Lipoprotein Profiles before Heparin Administration in Patients with or without Coronary Thrombosis Following Atherosclerosis.

Objective: The correlation between lipoproteins and arterial thrombosis is not fully elucidated, and no data exist in terms of lipoprotein profiles before heparin administration in patients with coronary arterial thrombosis (CAT). This cross-sectional study aimed to evaluate the lipoprotein profile before heparin administration in 63 ST-segment elevation myocardial infarction (STEMI) patients with CAT. Methods: The lipoprotein profile was measured via polyacrylamide gel electrophoresis prior to heparin administration for primary percutaneous coronary intervention for STEMI. Age- and sex-matched subjects with <25% stenosis in stable coronary artery disease were enrolled as controls. Results: In the pre-heparin serum, the fraction of very-low-density lipoprotein (P=0.75) in STEMI patients was not different from that in controls, and the fraction of intermediate-density lipoprotein (P<0.01) in STEMI patients was significantly lower than that in controls. Although the fraction of small dense low-density lipoprotein (s-LDL) in STEMI patients was significantly higher than that in controls (P<0.01), 44% (28/63) of STEMI patients were negative for s-LDL. Conclusion: Although lipoproteins are a risk factor for atherosclerosis, lipoprotein profiles with CAT following atherosclerosis in STEMI are different from those profiles without CAT in stable coronary artery disease.

Current status of hybrid intravascular ultrasound and optical coherence tomography catheter for coronary imaging and percutaneous coronary intervention.

Both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) play a crucial role in elucidating the pathophysiology of coronary artery disease (CAD) with the goal to improve patient outcomes of medical and/or interventional CAD management. However, no single intravascular imaging technique has been proven to provide complete and detailed evaluation of all CAD lesions due to some limitations. Although sequential use of multiple modalities may sometimes be performed, there may be issues related to risk, time, and cost. To overcome these problems, several hybrids involving dual-probe combined IVUS-OCT catheters have been developed. The aim of this review article is to demonstrate some limitations of stand-alone imaging devices for evaluation of CAD, summarize the advances in hybrid IVUS-OCT imaging devices, discuss the technical challenges, and present the potential value in the clinical setting, especially in patients receiving medical or interventional CAD management.

In Vivo Illustration of Dendrite Formation on a Mobile Thrombus within a Wallstent in an Iliac Artery: A Fractal Phenomenon.

The mechanism of stent thrombus formation following percutaneous transluminal stent implantation in an artery is unclear. This case report describes a 72-year-old man who had a mobile thrombus in a Wallstent in the right iliac artery despite daily oral administration of 100 mg of aspirin. This Wallstent was implanted 14 years ago. The unique in vivo angioscopic images show a solid mobile thrombus with some projections which rubbed yellow plaque on the stent struts.

In-stent restenosis assessed with frequency domain optical coherence tomography shows smooth coronary arterial healing process in second-generation drug-eluting stents.

INTRODUCTION: The pathophysiology and mechanism of in-stent restenosis (ISR) after implantation of second-generation drug-eluting stents (DESs) are not fully clear. We compared the morphological characteristics of ISR between first- and second-generation DESs using frequency domain optical coherence tomography (OCT). METHODS: Patients who underwent follow-up coronary angiography (CAG) after first-generation (CYPHER™ and TAXUS™) and second-generation (Nobori®, PROMUS Element™, Resolute Integrity and XIENCE) DES implantations were examined. ISR was defined as lesions of over 50% diameter stenosis at follow-up CAG. Frequency domain OCT was performed at the time of revascularisation of ISR. Tissue morphology was assessed at minimum lumen area. OCT images of DESs at both early (≤ 1 year) and late (> 1 year) phase follow-up were compared. RESULTS: On qualitative OCT assessment, the ratios of homogeneous, layered, heterogeneous without-attenuation and heterogeneous with-attenuation morphologies were 57.1%, 17.1%, 20.0% and 5.7%, respectively, for second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%, respectively, for first-generation DES ISR (n = 36). At late phase follow-up, homogeneous morphology was significantly more common for second-generation DES ISR compared to first-generation DES ISR (first-generation: 8.0% vs. second-generation: 50.0%; p < 0.01) while heterogeneous with-attenuation morphology was significantly more common for first-generation DES ISR (first-generation: 44.0% vs. second-generation: 5.6%; p < 0.01). CONCLUSION: Homogeneous tissue morphology was more frequently found for second-generation than first-generation DES ISR, especially in the late phase. This suggested that neointimal hyperplasia was the main mechanism in second-generation DES ISR, and that the neointima was stabilised, much like in bare metal stent implantation.

Outcome From a Randomized Controlled Clinical Trial　- Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).

BACKGROUND: The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. CONCLUSIONS: In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Clinical outcomes after tracheoplasty in patients with congenital tracheal stenosis in 1997-2014.

BACKGROUND: Mortality and morbidity of congenital tracheal stenosis (CTS) remain high. The aim of this study was to determine the factors predicting 12-month survival and 2-month successful extubation after tracheoplasty in patients with CTS. METHODS: Retrospective chart reviews were conducted in patients with CTS undergoing tracheoplasty at a single institution between 1997 and 2014. Patients' characteristics at disease onset and tracheoplasty were summarized. Twelve-month survival rate and 2-month extubation rate without tracheotomy after tracheoplasty were analyzed. RESULTS: We reviewed 81 patients' records. Multivariate analysis for 12-month survival revealed that older age (>2 months, hazard ratio [HR]: 0.08, 95% confidence interval [CI]: 0.02-0.36) or heavier body weight (>4.4 kg, HR: 0.13, 95% CI: 0.02-0.73) at tracheoplasty was a predictive factor for survival. Body weight at tracheoplasty (>8.2 kg, HR: 3.83, 95% CI: 1.88-7.79), preoperative balloon dilatation (HR: 0.30, 95% CI: 0.12-0.78), and carina involvement (HR: 0.36, 95% CI: 0.19-0.69) were predictive factors for successful extubation. CONCLUSIONS: Although CTS management is individualized, age or body weight at tracheoplasty needs to be considered and assessed for survival, as well as preoperative balloon dilatation, and carina involvement for successful extubation. LEVELS OF EVIDENCE: Level III.

Optical Frequency Domain Imaging Versus Intravascular Ultrasound in Percutaneous Coronary Intervention (OPINION Trial): Results From the OPINION Imaging Study.

OBJECTIVES: The authors sought to clarify how intravascular ultrasound (IVUS) and optical coherence tomography affect percutaneous coronary intervention (PCI) with current-generation drug-eluting stents in a pre-specified substudy of the OPINION (OPtical frequency domain imaging versus INtravascular ultrasound in percutaneous coronary interventiON) trial, a multicenter, prospective, randomized, noninferiority trial comparing optical frequency domain imaging (OFDI)-guided PCI with IVUS-guided PCI. BACKGROUND: The impact of these 2 imaging modalities in guiding PCI remains unknown. METHODS: Of 829 patients enrolled in the OPINION trial, 106 were included in the present imaging substudy. Their PCI was guided by either IVUS or OFDI, but all patients were imaged by both modalities after PCI and by OFDI at 8 months. Angiographic, OFDI, and IVUS images were analyzed by independent core laboratories, and statistical analysis was done independently by a dedicated institution. RESULTS: A total of 103 patients underwent either OFDI-guided (n = 54) or IVUS-guided (n = 49) PCI. Immediately after PCI, OFDI-guided PCI was associated with a smaller trend of minimum stent area (5.28 ± 1.65 mm2 vs. 6.12 ± 2.34 mm2; p = 0.088), fewer proximal stent-edge hematomas (p = 0.04), and fewer irregular protrusions (p = 0.014) than IVUS-guided PCI. At 8 months, the neointima area tended to be smaller in the OFDI-guided PCI group than in the IVUS-guided PCI group (0.56 ± 0.30 mm2 vs. 0.80 ± 0.65 mm2; p = 0.057), although the percentage of uncovered struts was significantly higher in the OFDI-guided PCI group than in the IVUS-guided PCI group (6.97 ± 7.03% vs. 4.67 ± 6.43%; p = 0.039). The minimum lumen area was comparable in both groups (p = 0.18). CONCLUSIONS: There were several differences in local findings between OFDI- and IVUS-guided PCI as expected given the different protocols for stent sizing in the 2 groups. The minimum lumen area at the 8-month follow-up was comparable, suggesting that OFDI- and IVUS-guided PCI are similarly feasible using the current-generation drug-eluting stents. (OPtical frequency domain imaging versus INtravascular ultrasound in percutaneous coronary interventiON; NCT01873222).

Optical frequency domain imaging vs. intravascular ultrasound in percutaneous coronary intervention (OPINION trial): one-year angiographic and clinical results.

AIMS: Optical frequency domain imaging (OFDI) is a recently developed, light-based, high-resolution intravascular imaging technique. Intravascular ultrasound (IVUS) is a widely used, conventional imaging technique for guiding percutaneous coronary intervention (PCI). We aimed to demonstrate the non-inferiority of OFDI-guided PCI compared with IVUS-guided PCI in terms of clinical outcomes. METHODS AND RESULTS: We did a prospective, multicentre, randomized (ratio 1:1), active-controlled, non-inferiority study to compare head-to-head OFDI vs. IVUS in patients undergoing PCI with a second generation drug-eluting stent. The primary endpoint was target vessel failure defined as a composite of cardiac death, target-vessel related myocardial infarction, and ischaemia-driven target vessel revascularization until 12 months after the PCI. The major secondary endpoint was angiographic binary restenosis at 8 months. We randomly allocated 829 patients to receive OFDI-guided PCI (n = 414) or IVUS-guided PCI (n = 415). Target vessel failure occurred in 21 (5.2%) of 401 patients undergoing OFDI-guided PCI, and 19 (4.9%) of 390 patients undergoing IVUS-guided PCI, demonstrating non-inferiority of OFDI-guided PCI to IVUS-guided PCI (hazard ratio 1.07, upper limit of one-sided 95% confidence interval 1.80; Pnon-inferiority = 0.042). With 89.8% angiographic follow-up, the rate of binary restenosis was comparable between OFDI-guided PCI and IVUS-guided PCI (in-stent: 1.6% vs. 1.6%, P = 1.00; and in-segment: 6.2% vs. 6.0%, P = 1.00). CONCLUSION: The 12-month clinical outcome in patients undergoing OFDI-guided PCI was non-inferior to that of patients undergoing IVUS-guided PCI. Both OFDI-guided and IVUS-guided PCI yielded excellent angiographic and clinical results, with very low rates of 8-month angiographic binary restenosis and 12-month target vessel failure. CLINICAL REGISTRATION: ClinicalTrials.gov, number NCT01873027.

Head-to-head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

OBJECTIVES: We sought to compare the efficacy and safety of prasugrel and ticagrelor in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). BACKGROUND: Evidence from randomized head-to-head comparison between prasugrel and ticagrelor is rare regarding clinical endpoints. METHODS: PubMed, the Cochrane Library, and Web of Science were queried with the terms "prasugrel," "ticagrelor," and "randomized." Relevant randomized controlled trials (RCTs) or the same terms were also surveyed using clinicaltrials.gov, escardio.org, pcronline.org, and tctmd.com. The clinical endpoints were death, myocardial infarction (MI), stroke, and stent thrombosis (ST) for efficacy, and any bleeding for safety. RESULTS: A total number of 2068 patients in 12 RCTs, whose longest follow-up period was 6 months, was included in this study. The risks of death (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.46-1.62, P = 0.647), MI (OR: 1.61, 95%CI: 0.71-3.62, P = 0.252), stroke (OR: 1.45, 95%CI: 0.25-8.36, P = 0.680), and ST (OR: 0.76, 95%CI: 0.20-2.81, P = 0.677) were similar between prasugrel and ticagrelor, respectively. While the incidence of bleeding according to the Bleeding Academic Research Consortium definitions was also comparable (OR: 0.83, 95%CI: 0.45-1.52, P = 0.539), that according to the Thrombolysis in Myocardial Infarction criteria was lower in prasugrel than ticagrelor (OR: 0.49, 95%CI: 0.24-0.97, P = 0.042). CONCLUSIONS: Although the efficacy was similar between prasugrel and ticagrelor, prasugrel may be associated with a lower risk of bleeding compared with ticagrelor during short- to mid-term follow-up period after PCI. Further studies are warranted in a larger patient population during longer-term follow up to validate these findings.

Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor.

OBJECTIVE: The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP). METHODS: The current study was a prospective, multicenter, open-label, single-arm, and exploratory clinical trial to evaluate the safety and efficacy of the TM regeneration procedure (TMRP). Myringotomy was used to mechanically disrupt the edge of the TMP, and a gelatin sponge immersed in bFGF was then placed over the perforation. Fibrin glue was dripped over the sponge as a sealant. TMP closure was examined 4 weeks later and, if insufficient, TMRP was repeated a maximum of three more times. TMP closure and hearing improvement 12 weeks after the final TMRP as well as safety were evaluated. RESULTS: Of the 11 patients with TMP who participated in this study, one who fulfilled the exclusion criteria and did not undergo TMRP and one with cholesteatoma were excluded from the efficacy analysis. TMP closure and hearing improvement 12 weeks after the final TMRP were achieved in eight out of nine patients (88.9%). Mean bone conduction threshold significantly improved 12 weeks after the TMRP compared with baseline (35.7±20.3 vs 29.4±21.0dB, P=0.015). Six out of ten patients receiving TMRP experienced temporary adverse events: appendicitis (serious, severe), otorrhea (mild), otitis media (mild), and sudden hearing loss (mild). However, none were related to the protocol treatment. CONCLUSION: TMP closure and hearing improvement were frequently confirmed following the TMRPs which were safely performed. These favorable outcomes were accompanied with significant improvement of the bone conduction threshold. These promising outcomes would encourage a large-scaled, randomized and pivotal clinical trial in the future. This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000006585).

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial.

BACKGROUND: The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. OBJECTIVES: This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. METHODS: Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. RESULTS: A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p < 0.001). Among patients with low SYNTAX scores (≤22), major cardiovascular events did not differ significantly between revascularization and medical therapy, either in the CABG stratum (26.1% vs. 29.9%, p = 0.41) or in the PCI stratum (17.8% vs. 19.2%, p = 0.84). Among patients with mid/high SYNTAX scores, however, major cardiovascular events were lower after revascularization than with medical therapy in the CABG stratum (15.3% vs. 30.3%, p = 0.02), but not in the PCI stratum (35.6% vs. 26.5%, p = 0.12). CONCLUSIONS: Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).

Design and baseline characteristics of the LANDMARK study.

BACKGROUND: Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. METHODS: The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5-6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range. If the target serum P level was not achieved, non-Ca-based P binders (other than LC) could also be added. The primary endpoint is survival time free of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction or stroke, and unstable angina. RESULTS: Overall, 2309 patients were allocated to the LC (N = 1154) or CC group (N = 1155). At baseline, the mean age was 68.4 years, 40.4 % were women, 55.9 % had diabetes, 18.3 % had a history of ischemic heart disease, and 13.9 % had cerebrovascular disease. A total of 184 patients (8.4 %) had undergone coronary intervention procedures. Baseline characteristics were well balanced between groups. CONCLUSIONS: The LANDMARK study will determine whether LC, a non-Ca-based P binder, reduces cardiovascular mortality and morbidity in chronic hemodialysis patients.