Events In Japanese Patients Research Articles

Impact of renal function on cardiovascular events in patients undergoing radical nephrectomy for renal cancer

To examine the actual impact of renal dysfunction on cardiovascular events in Japanese patients undergoing radical nephrectomy for renal cancer. This retrospective study included 178 Japanese patients who underwent radical nephrectomy between 1980 and 2010. Kaplan-Meier survival curves with a log-rank test and the Cox proportional hazards model were used to investigate the impact of the estimated glomerular filtration rate at 1 month after the radical nephrectomy on cardiovascular-event-free, cancer-specific and overall survivals. During a median follow up of 68 months, 23 patients experienced cardiovascular events and 32 died. Postoperative renal dysfunction (estimated glomerular filtration rate <45 mL/min/1.73 m(2) 1 month after radical nephrectomy) was a significant risk factor for postoperative cardiovascular events in addition to age and history of cardiovascular disease. After adjustment for preoperative characteristics, postoperative renal dysfunction increased the risk of cardiovascular events by 3.48-fold (95% confidence interval 1.28-8.66). For overall and cancer-specific survivals, postoperative renal dysfunction did not represent an independent risk factor. Renal dysfunction has a significant impact on cardiovascular events in patients undergoing radical nephrectomy for renal cancer.

Relationship between CHA2DS2-VASc scores and ischemic stroke/cardiovascular events in Japanese patients with paroxysmal atrial fibrillation without receiving anticoagulant therapy

The CHA(2)DS(2)-VASc score has been newly proposed for stratifying patients with nonvalvular atrial fibrillation (AF) according to the risk of ischemic stroke in the 2010 European Society of Cardiology guideline. However, there is little information about its usefulness for predicting long-term prognosis of cardiovascular events in Japanese patients with paroxysmal AF. This study retrospectively included 332 paroxysmal AF patients (224 men, mean age 65±13 years, mean follow-up period 53±35 months) without receiving anticoagulant therapy between June 1995 and August 2008 who were categorized into risk stratification on the basis of CHA(2)DS(2)-VASc score. The distribution of CHA(2)DS(2)-VASc scores was 0, 1, 2, 3, 4, 5, 6, and 7 points in 76 (23%), 60 (18%), 69 (21%), 69 (21%), 28 (8%), 23 (7%), 6 (2%), and 1 (0.3%) patients, respectively. The annual rates of symptomatic ischemic stroke were 0%, 0.60%, 0.95%, 1.96%, 5.45%, 9.06%, and 13.7% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5, and ≥6 points, respectively (p<0.001) and those of cardiovascular events including hospitalization for thromboembolism, heart failure and cardiovascular death were 0%, 1.43%, 1.50%, 2.52%, 10.14%, 12.85%, and 17.13% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5 and ≥6 points, respectively (p<0.001). Higher CHA(2)DS(2)-VASc scores were associated with greater annual rates of ischemic stroke and cardiovascular events. In a multivariate logistic regression analysis adjusted for the potentially confounding variables, the CHA(2)DS(2)-VASc score was associated with symptomatic ischemic stroke (odds ratio 7.051, 95% confidence interval 3.76-13.22, p<0.001) and cardiovascular events (odds ratio 3.448, 95% confidence interval 2.33-5.11, p<0.001). In Japanese patients with paroxysmal AF, the CHA(2)DS(2)-VASc score is a useful scheme for risk stratification of ischemic stroke and cardiovascular events.

Risk Factors for Cardiovascular Events in Japanese Patients Treated with Fluvastatin from the Long-Term Event Monitoring (LEM) Study

The long-term event monitoring (LEM) study evaluated the lipid-lowering efficacy and safety of fluvastatin in Japanese patients with hypercholesterolemia. The present sub-analysis focused on the impact of risk factors on event prevention. In the LEM study, patients (n=21,139) who started fluvastatin between 2000/4/1 and 2002/3/31 in Japan were prospectively registered and followed up for 3 years (secondary prevention cohort) or 5 years (primary prevention cohort). Of the patients registered, 19,084 were included in this sub-analysis. The secondary prevention group, demonstrated 8.27- and 2.89-fold higher incidence in cardiac events and cerebral events, respectively compared with the primary prevention group (P < 0.001). Complications of cerebrovascular disease demonstrated a 2.22- and 5.29-fold higher incidence in cardiac events and cerebral events (P < 0.01 and P < 0.001, respectively). Presence of diabetes mellitus (DM) in patients without complication significantly increased the incidence in both cardiac events (2.37) and cerebral events (2.15) as compared with non-DM patients for primary prevention (P < 0.001 and P < 0.01, respectively). For the secondary prevention, DM patients with complication of cardiac disease showed a significantly higher incidence in both cardiac events (1.59) and cerebral events (3.79) compared with non-DM patients (P < 0.05 and P < 0.01, respectively). In contrast, DM patients with complications of cerebrovascular disease showed a significantly higher incidence in cerebral events (2.58, P < 0.05), but not cardiac events compared with non-DM patients. Similarly, the presence of hypertension significantly increased the incidence in both cardiac (1.64) and cerebral events (1.81) for primary prevention (P < 0.01 and P < 0.05, respectively). For secondary prevention, hypertension in patients with complication of cardiac or cerebrovascular disease did not affect incidence in both cardiac and cerebral events. In the patients without complication, high triglycerides and low high density lipoprotein cholesterol (HDL-C), but not low density lipoprotein cholesterol (LDL-C), increased cerebral events, while only LDL-C significantly increased cardiac events. For secondary prevention, high triglycerides or low HDL-C, but not LDL-C, significantly increased the relative risk of cardiac events in the patients with complication of cardiac disease. The LEM study, a large-scale prospective study of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients, demonstrated high impact of complications such as DM and hypertension as well as high triglycerides or low HDL-C on cardiac and cerebral events. After long-term statin treatment, the control of other factors rather than LDL-C alone might be important to avoid vascular events.

Impact of Platelet Reactivity on Long-term Clinical Outcomes and Bleeding Events in Japanese Patients Receiving Antiplatelet Therapy with Aspirin

Aspirin is an antiplatelet drug widely used for the prevention of cardiovascular disease; however, it is known to increase bleeding events. A low response to aspirin was reported to correlate with poor prognosis in patients undergoing antiplatelet therapy with aspirin. The aim of this study was to evaluate the impact of the antiplatelet activity of aspirin on cardiovascular and bleeding events in Japanese patients. We analyzed the clinical course of 239 Japanese patients undergoing antiplatelet therapy with aspirin for a median of 64 months in this study. Their residual platelet reactivity was examined at enrollment and after 2 years. The co-primary endpoints were the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) and bleeding events. The annual incidence of MACCEs and major bleeding events was 3.7% and 0.48%, respectively. With defined criteria, 67 patients (28%) were classified as low responders based on the platelet aggregability measured at enrollment. Low response to aspirin was not associated with increased MACCEs, while it clearly increased MACCEs in patients less than 70 years old (low responders 36.9% vs. responders 14.8%, log rank p=0.008). Five major types of bleeding occurred in the responders, but not in low responders, although the difference was not statistically significant (p= 0.07). Low response to aspirin was not associated with the increase of long-term MACCEs, while it increased MACCEs in patients less than 70 years old; however, it tended to decrease major bleeding events in Japanese patients.

Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20)

To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. There were 90 cardiovascular events over 10,827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P < 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin. The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

Essential efficacy and safety profiles of everolimus in Japanese patients with metastatic renal cell carcinoma.

e15140 Background: Although the efficacy of sorafenib and sunitinib was similar in Asian and non-Asian patients with metastatic renal cell carcinoma (mRCC), large differences have been shown in the incidence of adverse events (AEs) in these populations. Due to limited data obtained from the RECORD-1 global study thus far (only 15 patients enrolled in the everolimus group), there is no strong evidence to support the efficacy and safety of everolimus in Japanese patients. Moreover, the incidence of interstitial lung diseases (ILD) in the temsirolimus Asian phase-II study was significantly higher as compared to Western phase-III data. Therefore, it is very important to establish the AE profile of everolimus in the Japanese population. Methods: The target patient population consisted of patients with advanced renal cell carcinoma who had been treated with everolimus since January 2010. Data on efficacy, PFS and response rate and safety were collected and demographic factors that could be correlated with efficacy and safety were carefully investigated. Data will be up-dated until May 2011, when the final data from approximately 150 cases will be shown. Results: Demographic data from 87 evaluable patients is as follows: mean age of 62 years; male to female ratio of 78:22; PS of 0 in 73%, 1 in 14%, 2-4 in 13%; histological diagnosis of clear cell carcinoma in 79%. Prior treatments were cytokines in 52%, sunitinib in 72%, and sorafenib in 60%. The reasons for discontinuation of prior therapy were progression (73%), adverse events (25%), and others (2%). Efficacy was demonstrated with a median PFS of 2.8 months and RR of PR7%/SD47%/PD20%. The incidence of adverse events (all grades) was 85% and discontinuation due to AEs was 30 %. Major AEs were stomatitis (45%), thrombocytopenia (25%), and anemia (24%).Serious adverse events (Grades 3-4) were anemia (9%), thrombocytopenia (6%), hyperglycemia (5%), and ILD (5%). Onset of adverse events was less than 28 days after starting the administration of everolimus. Conclusions: These findings suggest that everolimus was shown to be associated with relatively serious adverse events in Japanese patients and further up-date is necessary to provide an Asian AE profile of everolimus.

Calcium Channel Antagonists Prevent Cardiovascular Events in Japanese Patients With Myocardial Infarction Even in the Absence of Coronary Artery Spasm

Calcium Channel Antagonists Prevent Cardiovascular Events in Japanese Patients With Myocardial Infarction Even in the Absence of Coronary Artery Spasm

Bleeding Complications in Patients Undergoing Pulmonary Vein Isolation without Discontinuance of Warfarin

Background: Periprocedural anticoagulation with warfarin was reported to reduce the risk of stroke without increasing the risk of bleeding complications for radiofrequency catheter ablation of atrial fibrillation in US population. Methods and Results: The outcome of thromboembolic and hemorrhagic complication was surveyed in 20 consecutive patients who underwent pulmonary vein isolation in our hospital without discontinuance of warfarin. In these patients, the INR was aimed to keep >2.0. After the transseptal puncture, a heparin bolus (2000–5000 U) was administered, followed by additional heparin bolus and infusion to keep the activated clotting time (ACT) >350. As a result, no periprocedural stroke/transient ischemic attack was reported. Bleeding complications that need transfusion and/or prolongation of hospitarization occurred in 3 (15%) patients (1 cardiac tamponade, 1 massive hematoma, and 1 outside bleeding from venous puncture site). In 2 (10%) patients, ACT was inappropriately prolonged (>800) by initial 5000 U of heparin bolus. Conclusion: It is suggested that above mentioned control of periprocedural INR and ACT during procedure may increase hemorrhagic events in Japanese patients who undergo pulmonary vein isolation. In the case whose INR is >2.0, initial heparin bolus may be ristricted <5000 U to avoid inappropriate prolongation of ACT.

Comparison of Preventive Effect on Cardiovascular Events With Different Statins - The CIRCLE Study -

Although statins vary in their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) levels, there is little evidence that the degree of these changes can explain cardiac risk reduction in Japan. Our objective was to compare the efficacy of statins on serum lipid levels and to explore the association between those changes and cardiac events in patients after percutaneous coronary intervention (PCI). The 743 consecutive patients who underwent PCI from 2001 to 2008 were retrospectively investigated. Treatment with either atorvastatin or pitavastatin significantly reduced LDL-C compared with pravastatin or no statin. In contrast, only pitavastatin treatment significantly increased HDL-C (13.4 ± 22.9%, P=0.01 vs. no statin). Each statin significantly prevented major adverse cardiac events (MACE) compared with no statin, and pitavastatin was the most effective of all. Multivariate-adjusted analysis revealed that percent changes of both LDL-C and HDL-C independently predicted the incidence of MACE (hazard ratio [HR]: 1.015; 95% confidence interval [CI]: 1.010-1.020, HR: 0.988; 95%CI: 0.981-0.996, respectively). This relationship was preserved in patients with a baseline HDL-C level ≤ 45 mg/dl, but not HDL-C level > 45 mg/ml. The extent of changes in LDL-C and HDL-C with statin treatment would independently alter the risk of cardiac events in Japanese patients for secondary prevention. Statins with varying lipid-modifying ability might provide differing prognosis in patients after PCI.

Overall Survival and Updated Results from a Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma

In a phase II, open-label, multicentre Japanese study, sunitinib demonstrated antitumour activity and acceptable tolerability in metastatic renal cell carcinoma patients. Final survival analyses and updated results are reported. Fifty-one Japanese patients with a clear-cell component of metastatic renal cell carcinoma (25 treatment-naïve; 26 cytokine-refractory) received sunitinib 50 mg orally, once daily (Schedule 4/2). Overall and progression-free survivals were estimated by the Kaplan-Meier method. Objective response rate (per Response Evaluation Criteria in Solid Tumours) and safety were assessed with an updated follow-up. First-line and pretreated patients received a median 6.0 and 9.5 treatment cycles, respectively. Investigator-assessed, end-of-study objective response rate was 52.0, 53.8 and 52.9% in first-line, pretreated and overall intent-to-treat populations, respectively. The median progression-free survival was 12.2 and 10.6 months in first-line and pretreated patients, respectively. Fourteen patients per group died (56 and 54%), and the median overall survival was 33.1 and 32.5 months, respectively. The most common treatment-related Grade 3 or 4 adverse events and laboratory abnormalities were fatigue (24%), hand-foot syndrome (18%), decreased platelet count (55%), decreased neutrophil count (53%) and increased lipase (49%). No Grade 5 treatment-related adverse events occurred. Forty patients (78%) required dose reduction, and 13 (25%) discontinued, due to treatment-related adverse events. With the median overall survival benefit exceeding 2.5 years, and acceptable tolerability, in first-line and pretreated Japanese metastatic renal cell carcinoma patients with Eastern Cooperative Oncology Group performance status 0/1, sunitinib showed a favourable risk/benefit profile, similar to Western studies. However, there was a trend towards greater efficacy and more haematological adverse events in Japanese patients.

Prognostic Study of Cardiac and Renal Events in Japanese Patients With Chronic Kidney Disease and Cardiovascular Risk Using Myocardial Perfusion SPECT: J‐ACCESS 3 Study Design

Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease. Recent studies have indicated that the incidence of cardiovascular disease increases inversely with estimated glomerular filtration rate. Although coronary angiography is considered the gold standard for detecting coronary artery disease, contrast-induced nephropathy or cholesterol microembolization remain serious problems; therefore, a method of detecting coronary artery disease without renal deterioration is desirable. From this viewpoint, stress myocardial perfusion single photon emission computed tomography (SPECT) might be useful for patients with chronic kidney disease. We recently performed the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) investigating patients with suspected or extant coronary artery disease and the J-ACCESS 2 study of patients with diabetes. The findings from these studies showed that SPECT can detect coronary artery disease and help to predict future cardiac events. Thus, we proposed a multicenter, prospective cohort study called "J-ACCESS 3" in patients with chronic kidney disease and cardiovascular risk. The study aimed at predicting cardiovascular and renal events based on myocardial perfusion imaging and clinical backgrounds. We began enrolling patients in J-ACCESS 3 at 74 facilities from April 2009 and will continue to do so until 31 March 2010, with the aim of having a cohort of 800 patients. These will be followed up for three years. The primary endpoints will be cardiac death and sudden death. The secondary endpoints will comprise any cardiovascular or renal events. This study will be completed in 2013. Here, we describe the design of the J-ACCESS 3 study.

Long QT syndrome with compound mutations is associated with a more severe phenotype: A Japanese multicenter study

Long QT syndrome (LQTS) can be caused by mutations in the cardiac ion channels. Compound mutations occur at a frequency of 4% to 11% among genotyped LQTS cases. The purpose of this study was to determine the clinical characteristics and manner of onset of cardiac events in Japanese patients with LQTS and compound mutations. Six hundred three genotyped LQTS patients (310 probands and 293 family members) were divided into two groups: those with a single mutation (n = 568) and those with two mutations (n = 35). Clinical phenotypes were compared between the two groups. Of 310 genotyped probands, 26 (8.4%) had two mutations in the same or different LQTS-related genes (compound mutations). Among the 603 LQTS patients, compound mutation carriers had significantly longer QTc interval (510 ± 56 ms vs 478± 53 ms, P = .001) and younger age at onset of cardiac events (10 ± 8 years vs 18 ± 16 years, P = .043) than did single mutation carriers. The incidence rate of cardiac events before age 40 years and use of beta-blocker therapy among compound mutation carriers also were different than in single mutation carriers. Subgroup analysis showed more cardiac events in LQTS type 1 (LQT1) and type 2 (LQT2) compound mutations compared to single LQT1 and LQT2 mutations. Compound mutation carriers are associated with a more severe phenotype than single mutation carriers.

Sex differences in effects of valsartan administration on cardiovascular outcomes in hypertensive patients: findings from the Jikei Heart Study: Retracted

The randomized Jikei Heart Study has demonstrated that the addition of valsartan to conventional treatments prevents more cardiovascular events in Japanese patients with hypertension. This substudy analyses the sex difference in cardiovascular disease risk reduction in the Jikei Heart Study. Treatment effects were evaluated by sex (1038 women and 2043 men) as hazard ratios with 95% confidence intervals (CIs) using Cox regression models adjusted for age, BMI, smoking, dyslipidemia, diabetes, antihypertensives, and statin use at baseline. Women were older, had higher SBP, total and low-density lipoprotein cholesterol but were less frequently smokers or diabetics, and had a lower DBP and incidence of coronary artery disease. A greater incidence of primary endpoint, a composite of cardiovascular events, occurred in men versus women [hazard ratio 1.37 (95% CI 1.02-1.85)]. Men in the valsartan group had a significant reduction in the primary endpoint [hazard ratio 0.6 (95% CI 0.44-0.82), P = 0.001], whereas a nonsignificant effect was found in women [hazard ratio 0.64 (95% CI 0.39-1.06), P = 0.075]. However, statistical heterogeneity of this valsartan effect was not found between sexes, and women of at least 55 years of age, mostly after menopause, in the valsartan group showed a significant risk reduction for the primary endpoint [hazard ratio 0.60 (95% CI 0.36-0.99)]. The valsartan effect was significant in men and in elderly women but consistent in both sexes. A potential cardiovascular protection by valsartan therapy might be attributed to the cardiovascular risk level but not to the sex difference.

Oseltamivir-Induced Mania in a Patient With H1N1

Oseltamivir-Induced Mania in a Patient With H1N1

Obesity as a Risk Factor for Coronary Events in Japanese Patients with Hypercholesterolemia on Low-Dose Simvastatin Therapy

We previously reported that obesity (defined as a body mass index (BMI) >or=25 kg/m(2)) was not an independent risk factor for coronary heart disease (CHD) in hypercholesterolemic patients without a history of CHD from the Japan Lipid Intervention Trial (J-LIT). In this study, the obese J-LIT subgroup was further analyzed to assess CHD risk. In the J-LIT study, patients received simvastatin treatment (usually at 5 mg/day) for 6 years. A total of 38,385 patients (mean age: 57.7+/-7.9, 12,111 men) without prior CHD and/or stroke were analyzed. In this cohort, 181 CHD (acute myocardial infarction or sudden cardiac death) were observed. Obesity (n=12,929) was not an independent risk factor for CHD (relative risk; 1.18, 95% confidence interval; 0.87?1.59) after adjustment for the major risk known factors, such as age, sex, hypertension, diabetes mellitus (DM), and smoking. However, blood pressure, triglycerides, and fasting plasma glucose all increased, while high-density lipoprotein-cholesterol decreased, with increased BMI. The percentage of patients having two or three risk factors (such as dyslipidemia, hypertension, and DM) also increased with increased BMI. Obesity was not an independent risk factor for CHD in hypercholesterolemic patients on statin therapy; however, it is important to control obesity, a condition in which CHD risks accumulate, in order to improve associated risk factors along with the treatment of each risk factor, thus further reducing the risk of CHD.

Soluble adhesion molecule E-selectin predicts cardiovascular events in Japanese patients with type 2 diabetes mellitus

Soluble adhesion molecule E-selectin (sE-selectin) is a marker of endothelial activation. To investigate whether high serum concentrations of sE-selectin could predict cardiovascular events, we followed 392 Japanese patients with type 2 diabetes mellitus who had no history of cardiovascular disease for a mean period of 6 years. The cardiovascular end points were defined as fatal and nonfatal myocardial infarction, angina pectoris, stroke, and sudden death. During the follow-up period, 51 patients reached end point. Patients who reached end point were significantly older and had longer duration of diabetes, higher systolic blood pressure, higher hemoglobin A1c, higher plasma glucose, higher sE-selectin, and lower high-density lipoprotein cholesterol compared with those free of such events. The mean serum concentration of sE-selectin was higher in patients who reached end point (81.1 ± 32.2 ng/mL) than event-free patients (66.7 ± 33.7 ng/mL, mean ± SD; P < .01). Multiple logistic regression analysis identified age, systolic blood pressure, total cholesterol, sE-selectin, and low high-density lipoprotein cholesterol as independent factors related to cardiovascular events. The odds ratio for cardiovascular events for 1-SD increase in sE-selectin concentration was 1.45 (95% confidence interval, 1.22-1.71). Kaplan-Meier analysis demonstrated a significantly higher cardiovascular event rate in the highest tertile of sE-selectin compared with the lowest or middle tertile of sE-selectin ( P < .01). The results suggest that high serum concentrations of sE-selectin can predict cardiovascular events in Japanese patients with type 2 diabetes mellitus.

A Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma: Insights into the Treatment, Efficacy and Safety

This study aims to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (RCC). Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan-Meier method. In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%). In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.

Efficacy and safety of omalizumab in an Asian population with moderate‐to‐severe persistent asthma

The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma. Japanese patients (20-75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study. Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min (P = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab (P = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group. Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.

Normal myocardial perfusion scan portends a benign prognosis independent from the pretest probability of coronary artery disease. Sub-analysis of the J-ACCESS study

We assessed the usefulness of gated stress/rest 99mTc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) to predict ischemic cardiac events in Japanese patients with various estimated pretest probabilities of coronary artery disease (CAD). Of the 4031 consecutively registered patients for a J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT) study, 1904 patients without prior cardiac events were selected. Gated stress/rest myocardial perfusion SPECT was performed and segmental perfusion scores and quantitative gated SPECT results were derived. The pretest probability for having CAD was estimated using the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine guideline data for the management of patients with chronic stable angina, which includes age, gender, and type of chest discomfort. The patients were followed up for three years. During the three-year follow-up period, 96 developed ischemic cardiac events: 17 cardiac deaths, 8 nonfatal myocardial infarction, and 71 clinically driven revascularization. The summed stress score (SSS) was the most powerful independent predictor of all ischemic cardiac events (hazard ratio 1.077, CI 1.045-1.110). Abnormal SSS (> 3) was associated with a significantly higher cardiac event rate in patients with an intermediate to high pretest probability of CAD. Normal SSS (< or = 3) was associated with a low event rate in patients with any pretest probability of CAD. Myocardial perfusion SPECT is useful for further risk-stratification of patients with suspected CAD. The abnormal scan result (SSS > 3) is discriminative for subsequent cardiac events only in the groups with an intermediate to high pretest probability of CAD. The salient result is that normal scan results portend a benign prognosis independent from the pretest probability of CAD.

Error in Table in: Short Sleep Duration as an Independent Predictor of Cardiovascular Events in Japanese Patients With Hypertension

Error in Table in: Short Sleep Duration as an Independent Predictor of Cardiovascular Events in Japanese Patients With Hypertension