Kazuo Kimura

Backgrounds Atrial fibrillation (AF) is a risk factor for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD). The prognostic relevance of lower systolic blood pressure (SBP) and the optimal antithrombotic strategy in patients with AF and CAD remain to be clarified. Methods This post-hoc analysis of the AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease) trial stratified participants based on median SBP at baseline: >126 mmHg (High SBP group, n=1042) and ≤126 mmHg (Low SBP group, n=1093). The primary efficacy endpoint was a composite of cardiovascular events and all-cause death. The primary safety endpoint was major bleeding. Results The mean SBP was 139 mmHg and 114 mmHg in the High and Low SBP groups, respectively. In the propensity score-matched cohort (n=1684), the Low SBP group had a significantly higher incidence of the primary efficacy endpoint (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.01–1.88; p=0.039), while the primary safety endpoint was comparable between groups. In the Low SBP group, rivaroxaban monotherapy was associated with lower risks of both the primary efficacy (HR, 0.66; 95% CI, 0.41–0.86; p=0.006) and safety endpoints (HR, 0.40; 95% CI, 0.22–0.74; p=0.003) compared with combination therapy, whereas no significant differences were observed in the High SBP group. Conclusions Lower SBP was associated with increased risk of cardiovascular events and all-cause death. Rivaroxaban monotherapy demonstrated more favorable efficacy and safety outcomes compared with combination therapy, particularly among patients with lower SBP.

BACKGROUND: Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment. METHODS: In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (P =0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55–0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%; P =0.017). CONCLUSIONS: Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment. REGISTRATION: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000012069.

A recent meta‐analysis found no benefit of uric acid‐lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65–74 years and ≥ 75 years. Patients were randomized into febuxostat and non‐febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non‐fatal cerebral and cardiovascular events and all‐cause death. Patients aged ≥ 75 years exhibited more pre‐existing factors associated with cerebral and cardiorenovascular events than those aged 65–74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65–74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Background: Gut function is vital for human health, and defecation frequency can serve as a fundamental marker including various abnormal patterns. However, the link between a defecation pattern and future adverse events in patients with acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the association between defecation patterns during hospitalization and future cardiovascular events in patients with ACS. Methods: This two-center retrospective observational cohort study included 1949 patients hospitalized for ACS between 2012 and 2019. For a comprehensive assessment of defecation in a general ward, we examined three indicators: “frequency of non-defecation days,” “consecutive non-defecation days,” and “maximum daily defecation frequency,” in addition to “average daily defecation frequency”. Patients were divided according to Youden index-derived cutoff values of each defecation frequency indicators. The primary outcome was a composite of all-cause mortality, myocardial infarction, ischemic stroke, and hemorrhagic stroke. Results: During the follow-up period (median, 48 months; IQR 30–74 months), 405 of 1949 (20.8%) patients developed the primary outcome. In total, 229 patients died (96 cardiovascular deaths and 133 non-cardiovascular deaths), and there were 142, 57, 28, and 113 patients with non-fatal myocardial infarction, nonfatal ischemic stroke, nonfatal hemorrhagic stroke, and hospitalized due to heart failure, respectively. High “frequency of non-defecation days” (≥33.5%) (hazard ratio [HR], 1.507; 95% confidence interval [95%CI], 1.191–1.907; P =0.0006) and high “maximum daily defecations frequency” (≥ 5 times in a single day) (HR, 1.670; 95%CI, 1.203–2.317; P =0.002) were associated with an increased risk of future cardiovascular events in the multivariate models. High “frequency of non-defecation days” and high “maximum daily defecations frequency” exhibit distinct characteristics: the former was associated with long-term cardiovascular mortality, all-cause mortality, myocardial infarction, and cerebral hemorrhage, while the latter was linked to cancer-related mortality, non-cardiovascular mortality, cerebral infarction, and heart failure. Conclusions: Among patients with ACS who survived to discharge, abnormal defecation patterns as assessed by increased frequency of non-defecation days and high-frequency defecations within a single day, were independently associated with future cardiovascular events. Clinical Perspective: What Is New?: This is the first study to investigate defecation patterns during the acute phase in patients with ACS and utilize reliable records of defecation during hospitalization rather than relying on survey-based assessments. In patients with ACS, both increased frequency of non-defecation days and high-frequency defecations within a single day were independently associated with an increased risk of future cardiovascular events, controlling for various confounding factors including age, severity of ACS, medications, and dietary intake. What Are the Clinical Implications?: Abnormal defecation patterns, such as frequent non-defecation days and high-frequency defecations within a single day, serve as indicators of “gut frailty.” The presence of these abnormal defecation patterns may suggest a residual risk in patients post-ACS. Additional research is essential to explore the underlying mechanisms and potential therapeutic interventions.

Background: Thrombocytopenia poses a risk of bleeding in patients with chronic coronary syndrome after coronary intervention. However, whether thrombocytopenia also increases the bleeding risk in patients with atrial fibrillation and chronic coronary syndrome remains unclear. Methods and Results: This study evaluated the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Thrombocytopenia was defined as platelet count 3 level at enrollment. Primary end points included incidence of major bleeding based on the International Society on Thrombosis and Hemostasis criterion and major adverse cardiovascular ischemic events (cardiac death, myocardial infarction, and stroke). A total of 2133 patients were classified into the thrombocytopenia (n=70) and nonthrombocytopenia (n=2063) groups. Major bleeding was significantly higher in the thrombocytopenia group than in the nonthrombocytopenia group (10.0% versus 4.1%, P =0.027). The thrombocytopenia group tended to have a higher risk of major adverse cardiovascular ischemic events (11.4% versus 6.2%, P =0.08). The bleeding incidence was significantly higher in patients with thrombocytopenia receiving combination therapy with rivaroxaban and a single antiplatelet drug (thrombocytopenia group, 14.3%, versus nonthrombocytopenia group, 5.0%; hazard ratio, 3.18 [95% CI, 1.27–7.97], P =0.014). Thrombocytopenia was an independent predictor of major bleeding (hazard ratio, 2.57 [95% CI, 1.19–5.56], P =0.017). Conclusions: Among patients with atrial fibrillation and chronic coronary syndrome, thrombocytopenia was significantly associated with increased risk of major bleeding. Selecting drugs for patients with thrombocytopenia continuing antithrombotic therapy should be given special consideration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02642419. https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000016612.

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Purpose Inflammation plays an important role in the initiation and progression of atherosclerosis, leading to poor clinical outcomes. Hyperuricemia is associated with the activation of the Nod-like receptor protein 3 inflammasome. Here, we investigated whether inhibition of inflammation using febuxostat lowered the risk of cardiovascular events. Methods This is a post-hoc analysis of the randomized trial, Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED). In total, 1067 patients (736 men and 331 women) were included in the analysis. We compared the serial changes in high-sensitivity C-reactive protein (hs-CRP) levels between febuxostat and non-febuxostat groups and assessed the correlation between the changes in uric acid (UA) and hs-CRP levels after febuxostat treatment. We also determined whether febuxostat could reduce a hard endpoint, defined as a composite of cardiovascular events and all-cause mortality. Results Serum UA levels in the febuxostat group were significantly lower than those in the non-febuxostat group after randomization (p < 0.05). However, hs-CRP levels were comparable between the two groups during the study. No significant correlation was observed between the changes in UA and hs-CRP levels after febuxostat treatment. The hard endpoints did not differ significantly between the two groups. In patients with baseline hs-CRP levels > 0.2 mg/dL or those administered 40 mg of febuxostat, the drug did not reduce hs-CRP levels or decrease the hard endpoint. Conclusion Febuxostat reduced the UA levels but did not affect the CRP levels, and therefore may fail to improve cardiovascular outcomes after treatment. Trial Registration ClinicalTrial.gov (NCT01984749). https://clinicaltrials.gov/ct2/show/NCT01984749

Background: Dual antiplatelet therapy (DAPT) with aspirin plus P2Y12 inhibitor is used as a standard therapy for patients with acute myocardial infarction (AMI) treated with drug-eluting stents (DESs). In Japan, clopidogrel was the major P2Y12 inhibitor used for a decade until the new P2Y12 inhibitor, prasugrel, was introduced. Based on clinical studies considering Japanese features, the set dose for prasugrel was reduced to 20 mg as a loading dose (LD) and 3.75 mg as a maintenance dose (MD); these values are 60 and 10 mg, respectively, globally. Despite this dose discrepancy, little real-world clinical data regarding its efficacy and safety exist. Methods: From the K-ACTIVE registry, based on the DAPT regimen, patients were divided into a prasugrel group and a clopidogrel group. The ischemic event was a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The bleeding event was type 3 or 5 bleeding based on the Bleeding Academic Research Consortium (BARC) criteria. Results: Substantially more patients were prescribed prasugrel (n = 2786) than clopidogrel (n = 890). Clopidogrel tended to be selected over prasugrel in older patients with numerous comorbidities. Before adjustments were made, the cumulative incidence of ischemic events at 1 year was significantly greater in the clopidogrel group than in the prasugrel group (p = 0.007), while the cumulative incidence of bleeding events at 1 year was comparable between the groups (p = 0.131). After adjustments were made for the age, sex, body weight, creatine level, type of AMI, history of MI, approach site, oral anticoagulation therapy, presence of multivessel disease, Killip classification, and presence of intra-aortic balloon pumping, both ischemic and bleeding events became comparable between the groups. Conclusion: A Japanese dose of prasugrel was commonly used in AMI patients in the real-world database. Both the prasugrel and clopidogrel groups showed comparable rates of 1 year ischemic and bleeding events.

Acute cardiovascular disease, such as acute myocardial infarction and aortic disease, can lead to a serious life-threatening state within minutes to hours, so early accurate diagnosis, and appropriate treatment without delay are essential. To provide high-quality and timely treatment, 24-h availability of medical staff and cardiologists, as well as a cardiac catheterization laboratory are needed. In Japan, the number of patients with acute cardiovascular disease is increasing with the aging population and westernization of lifestyle; however, workstyle reforms for physicians, including a policy to limit overtime work, have been legislated. Under these conditions, it is necessary to centralize hospitals that treat cardiovascular emergency diseases as high-volume centers and build a patient triage system for allocating patients before hospital arrival. The prehospital 12-lead electrocardiogram (ECG) plays a central role in prehospital diagnosis and triage, and its importance will increase in future. We discuss the current and future state of the cardiovascular emergency medical care system utilizing prehospital 12-lead ECG in urban areas of Japan.