Antithrombotic therapy for stable coronary artery disease and atrial fibrillation in patients with and without revascularisation: the AFIRE trial.

BACKGROUND: The Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial demonstrated non-inferior efficacy endpoints for rivaroxaban monotherapy versus combination therapy (rivaroxaban plus a single antiplatelet) and superior safety endpoints in patients with atrial fibrillation and stable coronary artery disease. AIMS: This post hoc analysis investigated whether the AFIRE trial results reflected the presence or absence of prior revascularisation. METHODS: Among 2,215 patients, 1,697 (76.6%) had previously undergone revascularisation, and the remaining 518 (23.4%) had not undergone prior revascularisation. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation, or death from any cause, while the primary safety endpoint was major bleeding. RESULTS: In 1,697 patients with prior revascularisation, the efficacy and safety endpoints were superior for monotherapy versus combination therapy (efficacy: hazard ratio [HR] 0.62, 95% confidence interval [CI]: 0.45-0.85; p=0.003; safety: HR 0.62, 95% CI: 0.39-0.98; p=0.042). Among 518 without prior revascularisation, there were no significant differences in endpoints (efficacy: HR 1.19, 95% CI: 0.67-2.12; p=0.554; safety: HR 0.47, 95% CI: 0.18-1.26; p=0.134). There was borderline interaction of the efficacy endpoints (p=0.055) between two treatments. The safety benefit of monotherapy on any bleeding was significant in patients without prior revascularisation (HR 0.59, 95% CI: 0.38-0.93; p=0.022). CONCLUSIONS: In high-risk thrombosis patients with a history of prior revascularisation, rivaroxaban monotherapy versus combination therapy demonstrated favourable safety and efficacy outcomes.

Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention.

BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

Outcome after primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) may reduce the risk of subsequent cardiovascular events but remains challenging. The study aim was to evaluate the clinical characteristics and long-term outcomes of patients undergoing primary PCI for STEMI with CS. METHODS: We conducted an observational cohort study of patients with STEMI who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital. The primary outcome was cardiovascular death (CVD) during the median 3-year follow-up. We performed a landmark analysis for the incidence of CVD from 0 day to 1 year and from 1 to 10 years. RESULTS: Among the 1758 STEMI patients in the cohort, 212 (12.1 %) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4 % vs 2.9 %). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank p < 0.0001). Multivariate Cox regression analysis showed that CS was significantly associated with higher cardiovascular mortality (adjusted hazard ratio, 11.8; 95%confidence intervals, 7.78-18.1; p < 0.0001), but the mortality rates from 1 to 10 years were comparable (log-rank p = 0.68). CONCLUSION: The cardiovascular 1-year mortality rate for patients with STEMI was higher for those with CS on admission than without, but the mortality rates of >1 year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes.

Long-Term Impact of Renin-Angiotensin System Inhibitors for Secondary Prevention in Patients with Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention.

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.

Rationale and design of Juntendo Sarcopenia Registration to explore the predictors and prognosis of sarcopenia and frailty in the elderly in TOKYO (JUSTICE-TOKYO).

AIM: This study aimed to clarify the prevalence, predictors, and prognosis of frailty and sarcopenia in both cross-sectional and longitudinal study of the real world. METHODS: The JUSTICE-TOKYO study is a single-center, prospective observational study of elderly patients. Patients aged ≥65 years who regularly visited our center were enrolled and followed up for 4 years (n = 1042). The diagnosis of sarcopenia and frailty in the enrolled patients was based on the criteria established by the Asian Working Group for Sarcopenia and Japanese version of the Cardiovascular Health Study criteria, respectively. The primary end point is the incidence of all-cause mortality and hospitalization for treatment. The secondary end points are clinically significant bleeding, cardiovascular events, strokes, malignancies, incidence of falling, fractures, pneumonia, and the onset of new dementia cases. RESULTS: A total of 1042 patients were enrolled in this study. The mean age of the cohort at baseline was 78.2 years, with 56% being women. Among the enrolled patients, 223 (21.4%) diagnosed with sarcopenia, 172 (16.5%) exhibited frailty, and 541 (51.9%) fell into the prefrailty category. CONCLUSIONS: The JUSTICE-TOKYO study provides valuable insights into the prevalence of sarcopenia and frailty among older adult outpatients in a real-world context and contributes to measures aimed at extending healthy life expectancy. Geriatr Gerontol Int 2024; 24: 168-172.

Clinical outcomes of ST elevation myocardial infarction patients without standard modifiable risk factors.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes mellitus, dyslipidemia, and smoking) are widely recognized as risk factors for coronary artery disease. However, the associations between absence of SMuRFs and long-term clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients are unclear. METHODS: Consecutive STEMI patients who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 were retrospectively analyzed. The primary endpoint was up to 5-year all-cause mortality. Clinical characteristics and outcomes were compared between patients with at least one of the SMuRFs and those without any SMuRFs. RESULTS: Of 1963 STEMI patients, 126 (6.4 %) did not have any SMuRFs. Patients without SMuRFs were significantly older, had lower body mass index, and were more likely to be female. During a median follow-up period of 4.9 years, the cumulative incidence of death was significantly higher in patients without SMuRFs than in those with SMuRFs (log-rank p < 0.0001). Landmark analysis showed that patients without SMuRFs had higher mortality within 30 days of STEMI onset (log-rank p = 0.0045) and >30 days after STEMI onset (log-rank p = 0.0004). Multivariable Cox hazards analysis showed that absence of SMuRFs was associated with a higher risk of mortality (hazard ratio, 1.59; 95 % confidence interval, 1.14-2.21; p = 0.006). CONCLUSIONS: Of STEMI patients undergoing primary PCI, patients without any SMuRFs had higher mortality than those with at least one of the SMuRFs. Patients without any SMuRFs have a poor prognosis and require more attention.

Cross-Sectional Study on the Association between Dietary Patterns and Sarcopenia in Elderly Patients with Chronic Kidney Disease Receiving Conservative Treatment.

Sarcopenia is a poor prognostic factor in patients with chronic kidney disease (CKD). Adequate dietary patterns are important for preventing sarcopenia; however, evidence regarding the underlying association between sarcopenia and diet is insufficient. Therefore, in this study, we aimed to investigate the association between sarcopenia and dietary patterns in CKD patients receiving conservative treatment. In this cross-sectional study, 441 patients with conservative CKD were examined using the Asian Working Group for Sarcopenia diagnostic criteria. CKD was defined as an eGFR of <60 mL/min/1.73 m2 present for >3 months. The participants were divided into sarcopenia and non-sarcopenia groups, and dietary patterns were compared between the two groups using the dietary variety score, a simple dietary survey method that investigates the weekly frequency of consumption of 10 food groups. Logistic regression analysis for CKD G3 showed that female sex (odds ratio (OR): 0.166, 95% confidence interval (CI): 0.086-0.320), increased body mass index (OR: 0.663, 95% CI: 0.590-0.745), and almost daily consumption of green/yellow vegetables (OR: 0.350, 95% CI: 0.176-0.695) were positively associated with non-sarcopenia. Although further prospective studies are required, the results suggest that low frequent consumption of vegetables is associated with sarcopenia in patients with CKD.

Thrombocytopenia as a Bleeding Risk Factor in Atrial Fibrillation and Coronary Artery Disease: Insights From the AFIRE Study.

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 <100 000/mm3 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.

External Validation of the HELT-E2S2 Score in Japanese Patients With Nonvalvular Atrial Fibrillation　- A Pooled Analysis of the RAFFINE and SAKURA Registries.

BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.Methods and Results: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166

Differential prediction of high-sensitivity cardiac troponin-I, but not N-terminal pro-brain natriuretic peptide, in different pitavastatin doses on cardiovascular events in stable coronary artery disease.

BACKGROUND: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin. METHODS: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline. RESULTS: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001). CONCLUSIONS: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.

Phenotyping of atrial fibrillation with cluster analysis and external validation.

OBJECTIVES: Atrial fibrillation (AF) is a heterogeneous condition. We performed a cluster analysis in a cohort of patients with AF and assessed the prognostic implication of the identified cluster phenotypes. METHODS: We used two multicentre, prospective, observational registries of AF: the SAKURA AF registry (Real World Survey of Atrial Fibrillation Patients Treated with Warfarin and Non-vitamin K Antagonist Oral Anticoagulants) (n=3055, derivation cohort) and the RAFFINE registry (Registry of Japanese Patients with Atrial Fibrillation Focused on anticoagulant therapy in New Era) (n=3852, validation cohort). Cluster analysis was performed by the K-prototype method with 14 clinical variables. The endpoints were all-cause mortality and composite cardiovascular events. RESULTS: The analysis subclassified derivation cohort patients into five clusters. Cluster 1 (n=414, 13.6%) was characterised by younger men with a low prevalence of comorbidities; cluster 2 (n=1003, 32.8%) by a high prevalence of hypertension; cluster 3 (n=517, 16.9%) by older patients without hypertension; cluster 4 (n=652, 21.3%) by the oldest patients, who were mainly female and with a high prevalence of heart failure history; and cluster 5 (n=469, 15.3%) by older patients with high prevalence of diabetes and ischaemic heart disease. During follow-up, the risk of all-cause mortality and composite cardiovascular events increased across clusters (log-rank p<0.001, p<0.001). Similar results were found in the external validation cohort. CONCLUSIONS: Machine learning-based cluster analysis identified five different phenotypes of AF with unique clinical characteristics and different clinical outcomes. The use of these phenotypes may help identify high-risk patients with AF.

Risk prediction score for clinical outcome in atrial fibrillation and stable coronary artery disease.

OBJECTIVE: Antithrombotic therapy is essential for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) because of the high risk of thrombosis, whereas a combination of antiplatelets and anticoagulants is associated with a high risk of bleeding. We sought to develop and validate a machine-learning-based model to predict future adverse events. METHODS: Data from 2215 patients with AF and stable CAD enrolled in the Atrial Fibrillation and Ischaemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease trial were randomly assigned to the development and validation cohorts. Using the random survival forest (RSF) and Cox regression models, risk scores were developed for net adverse clinical events (NACE) defined as all-cause death, myocardial infarction, stroke or major bleeding. RESULTS: Using variables selected by the Boruta algorithm, RSF and Cox models demonstrated acceptable discrimination and calibration in the validation cohort. Using the variables weighted by HR (age, sex, body mass index, systolic blood pressure, alcohol consumption, creatinine clearance, heart failure, diabetes, antiplatelet use and AF type), an integer-based risk score for NACE was developed and classified patients into three risk groups: low (0-4 points), intermediate (5-8) and high (≥9). In both cohorts, the integer-based risk score performed well, with acceptable discrimination (area under the curve 0.70 and 0.66, respectively) and calibration (p>0.40 for both). Decision curve analysis showed the superior net benefits of the risk score. CONCLUSIONS: This risk score can predict the risk of NACE in patients with AF and stable CAD. TRIAL REGISTRATION NUMBERS: UMIN000016612, NCT02642419.

Impact of Low-Dose Prasugrel on Platelet Reactivity in Chronic Phase of Post-Percutaneous Coronary Intervention (CHAPERON): a Prospective Cohort Study.

PURPOSE: Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5 mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). METHODS: A total of 348 patients were studied. PRU was measured 6-12 months after PCI and subsequently, 6 months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. RESULTS: At baseline, 136 patients (39%) received prasugrel 3.75 mg, 48 patients (14%) received prasugrel 2.5 mg, and 164 patients (47%) received clopidogrel 75 mg. Clopidogrel 75 mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75 mg. In addition, switching from clopidogrel 75 mg to prasugrel 2.5 mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75 mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75 mg. CONCLUSIONS: Prasugrel 2.5 mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).

Impact of Multivessel Percutaneous Coronary Intervention vs. Culprit Vessel Percutaneous Coronary Intervention in Patients with Acute Coronary Syndromes and Multivessel Coronary Artery Disease.

BACKGROUND: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting. METHODS: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS. RESULTS: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008). CONCLUSION: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI.

Clinical features and predictors of non-cardiac death in patients hospitalised for acute myocardial infarction: Insights from the Tokyo CCU network multicentre registry.

BACKGROUND: Patients with acute myocardial infarction (AMI) commonly have multiple comorbidities, and some die in hospitals due to causes other than cardiac complications. However, limited information is available on noncardiac death in patients hospitalised for AMI. Therefore, the present study was performed to determine the incidence, annual trend, clinical characteristics, and predictors of in-hospital non-cardiac death in patients with AMI using the Tokyo Cardiovascular Care Unit (CCU) network registry. METHODS: The registry included 38,589 consecutive patients with AMI who were admitted to the CCU between 2010 and 2019. The primary endpoint was in-hospital noncardiac death. Further, predictors of cardiac and non-cardiac death were identified. RESULTS: The incidence of all-cause in-hospital mortality was 7.0% (n = 2700), and the proportion of mortality was 15.6% (n = 420) and 84.4% (n = 2280) for noncardiac and cardiac causes, respectively. The proportion of noncardiac deaths did not change annually over the last decade (p = 0.66). After adjusting for all variables, age, Killip classification grade, peak creatine kinase, hemoglobin, serum creatinine, and C-reactive protein were common predictors of cardiac and non-cardiac deaths. Indicators of malnutrition, such as lower body mass index (kg/m2) [odds 0.94, 95%CI (0.90-0.97), p < 0.001] and serum low-density lipoprotein cholesterol level (per 10 mg/dl) [odds 0.92, 95%CI (0.89-0.96), p < 0.001] were the specific predictors for non-cardiac deaths. CONCLUSIONS: The incidence of in-hospital noncardiac death was significant in patients with AMI, accounting for 15.6% of all in-hospital mortalities. Thus, prevention and management of non-cardiac complications are vital to improve acute-phase outcomes, especially those with predictors of non-cardiac death.

Impact of atrial fibrillation type (paroxysmal vs. non-paroxysmal) on long-term clinical outcomes: The RAFFINE registry subanalysis.

BACKGROUND: The type of atrial fibrillation (AF) (paroxysmal or non-paroxysmal) is important in determining its therapeutic management. However, the prognostic impact of AF type on the incidence of cardiovascular events remains uncertain. METHODS: We investigated patients with AF who were selected from an observational, multicenter, prospective registry (RAFFINE) comprising 4 university hospitals and 50 general hospitals/clinics in Japan between 2013 and 2015. In this subanalysis study, patients were divided into two groups according to their AF pattern at the time of enrollment. The primary outcome was the composite of death, ischemic stroke, and heart-failure-related hospitalization. RESULTS: Among 3845 patients, 1472 (38.3 %) and 2373 (61.7 %) had paroxysmal and non-paroxysmal type AF, respectively. Patients with non-paroxysmal AF were older and had higher CHADS2 score and prevalence of comorbidities. During median follow-up of 3.7 years, 681 (17.7 %) primary endpoints were identified. Cumulative incidences of the primary endpoint were significantly higher in the non-paroxysmal AF group; however, rates of bleeding events were not significantly different between the groups. Multivariate Cox hazard analysis showed that non-paroxysmal AF had significantly higher risk of cardiovascular events compared with paroxysmal AF (hazard ratio, 1.38; 95 % confidence interval, 1.17-1.64; p = 0.0002). CONCLUSIONS: Non-paroxysmal AF was significantly associated with cardiovascular events. Long-term clinical outcomes might be improved if transition from paroxysmal to non-paroxysmal AF can be prevented.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Low-Density Lipoprotein Cholesterol Levels on Statins and Cardiovascular Event Risk in Stable Coronary Artery Disease　- An Observation From the REAL-CAD Study.

BACKGROUND: The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins.Methods and Results: From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11,105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (<70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL). The primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70-100 mg/dL group (reference) was not significantly different for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58-1.18, P=0.32, and HR 1.25, 95% CI 0.88-1.79, P=0.22). The adjusted risk of the LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60-1.11, P=0.21), whereas it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08-5.17, P<0.001). CONCLUSIONS: A very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70-100 mg/dL) in patients receiving the same doses of statins.