Validation of a New Scoring Method to Assess the Efficacy of Rapid Initiation and Titration of Combination Pharmacotherapy for Patients Hospitalized with Acute Decompensated Heart Failure with Reduced and Mildly Reduced Ejection Fraction.

Background: Despite the encouragement of early initiation and titration of guideline-directed medical therapy (GDMT) for the treatment of heart failure (HF), most patients do not receive an adequate type and dose of pharmacotherapy in the real world. Objectives: This study aimed to determine the efficacy of titrating composite GDMT in patients with HF with reduced and mildly reduced ejection fraction and to identify patient conditions that may benefit from titration of GDMT. Methods: This was a two-center, retrospective study of consecutive patients hospitalized with acute decompensated heart failure (ADHF). Patients were classified into two groups according to a scoring scale determined by combination and doses of four types of HF agents (ACEis/ARBs/ARNis, BBs, MRAs, and SGLT2is) at discharge. A score of 5 or greater was defined as titrated GDMT, and a score of 4 or less was regarded as sub-optimal medical therapy (MT). Results: A total of 979 ADHF patients were screened. After 553 patients were excluded based on exclusion criteria, 426 patients (90 patients in the titrated GDMT group and 336 patients in the sub-optimal MT group) were enrolled for the analysis. The median follow-up period was 612 (453-798) days. Following statistical adjustment using the propensity score weighting method, the 2-year composite endpoint (composite of cardiac death and HF rehospitalization) rate was significantly lower in the titrated GDMT group, at 19%, compared with the sub-optimal MT group: 31% (score 3-4 points) and 43% (score 0-2 points). Subgroup analysis indicated a marked benefit of titrated GDMT in particular patient subgroups: age < 80 years, BMI 19.0-24.9, eGFR > 20 mL/min/1.73 m2, and serum potassium level ≤ 5.5 mmol/L. Conclusions: Prompt initiation and dose adjustment of multiple HF medications, with careful monitoring of the patient's physiologic and laboratory values, is a prerequisite for improving the prognosis of patients with heart failure.

Clinical Efficacy of Pre-Hospital Electrocardiogram Transmission in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Rapid reperfusion by primary percutaneous coronary intervention (pPCI) is an established strategy for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Pre-hospital electrocardiogram (PH-ECG) transmission by the emergency medical services (EMS) facilitates timely reperfusion in these patients. However, evidence regarding the clinical benefits of PH-ECG in individual hospitals is limited.This retrospective, observational study investigated the clinical efficacy of PH-ECG in STEMI patients who underwent pPCI. Of a total of 382 consecutive STEMI patients, 237 were enrolled in the study and divided into 2 groups: a PH-ECG group (n = 77) and non-PH-ECG group (n = 160). Door-to-balloon time (D2BT) was significantly shorter in the PH-ECG group (66 [52-80] min), compared to the non-PH-ECG group (70 [57-88] minutes, P = 0.01). The 30-day all-cause mortality rate was 6% in the PH-ECG group, which was significantly lower than that in the non-PH-ECG group (16%) (P = 0.037, hazard ratio [HR]: 0.38, 95% CI: 0.15-0.98). This trend was particularly evident in severely ill patients when stratified by GRACE score.The use of PH-ECG improved the survival rate of STEMI patients undergoing pPCI due to the improved pre-arrival preparation based on the EMS information. Coordination between EMS and PCI-capable institutes is essential for the management of PH-ECG.

Case-fatality rate of major bleeding events in patients on dual antiplatelet therapy after percutaneous coronary intervention: A systematic review and meta-analysis.

Background: Assessment of the case-fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI). Objectives: To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT. Methods: Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic. Results: Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow-up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1-16.2; I 2 = 50%) in the entire study population, and 13.8% (95% CI, 6.5-27.1; I 2 = 28%), 11.2% (95% CI, 6.7-18.0; I 2 = 0%), and 5.8% (95% CI, 3.0-11.1; I 2 = 0%) in those on short-term (≤6 months; n = 16,553), standard-term (12 months; n = 19,453), and long-term DAPT (>12 months; n = 10,238), respectively. Conclusion: Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long-term DAPT.

Distinct propagation patterns of right pulmonary veins through multiple epicardial connections during right atrial pacing and sinus rhythm.

A 47-year-old man with symptomatic paroxysmal atrial fibrillation (AF) underwent AF ablation. Activation maps during right atrial pacing and sinus rhythm before the ablation revealed distinctive left atrial (LA) propagations with multiple LA breakthrough sites via epicardial connections. A wide area circumferential ablation was not able to achieve a right pulmonary vein (RPV) isolation and required an inner PV ablation to isolate the RPV. Activation maps during different rhythms before the ablation may be helpful to unmask multiple epicardial connections between the RPV and right atrium.

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study.

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Long-Term Clinical Outcomes After Filter Protection During Percutaneous Coronary Intervention in Patients With Attenuated Plaque　- 1-Year Follow up of the VAMPIRE 3 (Vacuum Aspiration Thrombus Reemoval 3) Trial.

BACKGROUND: Selective use of distal filter protection during percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) decreased the incidence of no-reflow phenomena and in-hospital serious adverse cardiac events compared with conventional PCI in patients with attenuated plaque ≥5 mm; however, its long-term clinical outcome remains unknown.Methods and Results:Patients who had ACS with attenuated plaque ≥5 mm were assigned to receive distal protection (DP) (n=98) or conventional treatment (CT) (n=96). The rate of major adverse cardiovascular events (MACE), a composite of death from any cause, non-fatal myocardial infarction, or target vessel revascularization (TVR) at 1 year, was the pre-specified secondary endpoint of the trial. MACE at 1 year occurred in 12 patients (12.2%) in the DP group and 3 patients (3.1%) in the CT group (P=0.029), which was driven by a higher risk of TVR (11 [11.2%] vs. 2 [2.1%], P=0.018). In patients treated with bare-metal stents (n=42), MACE occurred in 25.0% of the patients in the DP group and in none of the patients in the CT group (P=0.029), whereas in patients treated with drug-eluting stents (n=151), rates of MACE were similar in the groups (8.1% vs. 3.9%, P=0.32). CONCLUSIONS: In ACS patients with attenuated plaque ≥5 mm, the 1-year rates of MACE were higher in the DP group than in the CT group. This effect might be mitigated by the use of drug-eluting stents.

Safety and efficacy of uninterrupted treatment with edoxaban or warfarin during the peri-procedural period of catheter ablation for atrial fibrillation.

BACKGROUND: The real-world safety and efficacy of uninterrupted anticoagulation treatment with edoxaban (EDX) or warfarin (WFR) during the peri-procedural period of catheter ablation (CA) for atrial fibrillation (AF) are yet to be investigated. METHODS: We conducted a two-center experience, observational study to retrospectively investigate consecutive patients who underwent CA for AF and received EDX or WFR. We examined the incidence of thromboembolic and bleeding complications during the peri-procedural period. RESULTS: The EDX and WFR groups included 153 and 103 patients, respectively (total: 256 patients). Demise or thromboembolic events did not occur in either of the groups. The incidence of major bleeding in the EDX and WFR groups was 0.7% and 2.9%, respectively. The total incidence of major/minor bleeding in the EDX and WFR groups was 7.8% and 8.7%, respectively. Of note, the incidence of bleeding complications in the uninterrupted WFR strategy group was markedly high in patients with an estimated glomerular filtration rate (eGFR) <30 (75%) or a HAS-BLED score ≥3 (60%). Patients with eGFR ≥30 and a HAS-BLED score ≤2 had a lower incidence of bleeding (<10%), regardless of the administered anticoagulation drug (EDX or WFR). CONCLUSIONS: This study confirmed the safety and efficacy of uninterrupted anticoagulation therapy using EDX or WFR in real-world patients undergoing CA for AF. Patients with severely impaired renal function and/or a higher bleeding risk during uninterrupted therapy with WFR were at a prominent risk of bleeding. Therefore, particular attention should be paid in the treatment of these patients.

Association between High Platelet Reactivity Following Dual Antiplatelet Therapy and Ischemic Events in Japanese Patients with Coronary Artery Disease Undergoing Stent Implantation.

AIM: Although high on-treatment platelet reactivity (HTPR) with dual antiplatelet therapy (DAPT) correlates with long-term adverse outcomes in patients undergoing percutaneous coronary intervention, the correlation in Japanese patients remains unclear. Therefore, we examined the relationship between platelet reactivity during DAPT with aspirin and clopidogrel and 1-year clinical outcomes following successful coronary stent implantation. METHODS: A prospective, multicenter registry study (j-CHIPS) was conducted in patients undergoing coronary stenting and receiving aspirin and clopidogrel at 16 hospitals in Japan. A VerifyNow point-of-care assay was used to assess platelet reactivity, and a cutoff value to define HTPR was established. RESULTS: Between February 2011 and May 2013, 1047 patients were prospectively enrolled, of which 854 patients with platelet function evaluation at 12-24 h after PCI were included in the final analysis. After 1 year of follow-up, the incidence of the primary endpoint (a composite of all-cause mortality, myocardial infarction, stent thrombosis, and ischemic stroke) was significantly higher in patients with HTPR than in those without (5.9% vs. 1.5%, p=0.008), and HTPR showed a modest ability to discriminate between patients who did and did not experience major adverse cardiac and cerebrovascular events (area under the curve, 0.60; 95% confidence interval, 0.511-0.688, p=0.039). HTPR status did not identify patients at risk for major or minor bleeding events. CONCLUSION: HTPR was significantly associated with adverse ischemic outcomes at 1 year after PCI in Japanese patients receiving maintenance DAPT, indicating its potential as a prognostic indicator of clinical outcomes in this high-risk patient population.

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study.

AIMS: To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target. MATERIALS AND METHODS: This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group. RESULTS: Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007). CONCLUSIONS: This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.

Systematic review with meta-analysis: the risk of gastrointestinal bleeding in patients taking third-generation P2Y12 inhibitors compared with clopidogrel.

BACKGROUND: Ticagrelor and prasugrel are third-generation oral P2Y12 receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel. AIM: To compare the risk of gastrointestinal bleeding (GIB) among users of third-generation P2Y12 inhibitors with clopidogrel. METHODS: We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third-generation P2Y12 inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non-coronary artery bypass graft (CABG) major bleeding, life-threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes. RESULTS: Forty-one studies were included in the analysis of non-CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third-generation P2Y12 inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13-1.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05-1.67) and unspecified GIB (RR 1.25, 95% CI 1.01-1.53), but not lower GIB (RR 1.25, 95% CI 0.95-1.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10-1.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94-1.39). Third-generation P2Y12 inhibitors also increased the risk of non-CABG major bleeding (RR 1.18, 95% CI 1.08-1.28). CONCLUSION: Third-generation P2Y12 inhibitors were associated with increased risk of GIB and non-CABG major bleeding when compared with clopidogrel.

A Randomized Study of Distal Filter Protection Versus Conventional Treatment During Percutaneous Coronary Intervention in Patients With Attenuated Plaque Identified by Intravascular Ultrasound.

OBJECTIVES: The aim of this study was to evaluate the utility of distal protection during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes at high risk for distal embolization. BACKGROUND: The results of previous clinical trials indicated that the routine use of distal protection in patients with ST-segment elevation myocardial infarction did not improve clinical outcomes. However, selective use of distal protection by means of a filter-based distal protection system has not been evaluated. METHODS: Two hundred patients with acute coronary syndromes who had native coronary artery lesions and attenuated plaque with longitudinal length ≥5 mm on pre-PCI intravascular ultrasound were randomly assigned to undergo PCI with distal protection or conventional treatment. RESULTS: The primary endpoint (no-reflow phenomenon) occurred in 26 patients (26.5%) in the distal protection group and 39 patients (41.7%) in the conventional treatment group (p = 0.026), and the corrected TIMI (Thrombolysis In Myocardial Infarction) frame count after revascularization was significantly lower in the distal protection group (23 vs. 30.5; p = 0.0003). The incidence of cardiac death, cardiac arrest, cardiogenic shock after revascularization requiring defibrillation, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation was significantly lower in the distal protection group than in the conventional treatment group (0% vs. 5.2%; p = 0.028). CONCLUSIONS: The use of distal embolic protection applied with a filter device decreased the incidence of the no-reflow phenomenon and was associated with fewer serious adverse cardiac events after revascularization than conventional PCI in patients with acute coronary syndromes with attenuated plaque ≥5 mm in length. (Assessment of Distal Protection Device in Patients at High Risk for Distal Embolism in Acute Coronary Syndrome [ACS] [VAMPIRE3]; NCT01460966).

Effect of QRS Morphology and Duration on Clinical Outcomes After Cardiac Resynchronization Therapy　- Analysis of Japanese Multicenter Registry.

BACKGROUND: QRS duration (QRSd) and morphology are established response predictors of cardiac resynchronization therapy (CRT). However, evidence in Japanese populations is lacking.Methods and Results:We retrospectively analyzed the Japanese multicenter CRT database. We divided patients according to their intrinsic QRSd and morphology, and assessed echocardiographic responses and clinical outcomes. The primary endpoint was a composite of all-cause death or hospitalization because of heart failure. A total of 510 patients were enrolled: 200 (39%) had left bundle branch block (LBBB) and QRSd ≥150 ms; 80 (16%) had LBBB (QRSd: 120-149 ms); 61 (12%) had non-LBBB (NLBBB) (QRSd: ≥150 ms); 54 (11%) had NLBBB (QRSd: 120-149 ms); 115 (23%), narrow (<120 ms). The proportion of echocardiographic responders was higher in LBBB (QRSd ≥150 ms) [74% vs. 51% vs. 38% vs. 52% vs. 50%, LBBB (QRSd ≥150 ms) vs. LBBB (QRSd 120-149 ms) vs. NLBBB (QRSd ≥150 ms) vs. NLBBB (QRSd 120-149 ms) vs. narrow, respectively, P<0.001]. During follow-up (3.2±1.5 years), the incidence of the primary endpoint was lowest in the LBBB group (QRSd ≥150) (28.6% vs. 42.3% vs. 45.9% vs. 55.6% vs. 55.3%, respectively, P<0.001). This difference was still significant after adjusting for other baseline characteristics. CONCLUSIONS: In this Japanese patient population, LBBB intrinsic QRS morphology and prolonged QRSd (≥150 ms) exhibited the best response to CRT.

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

OBJECTIVE: Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). RESEARCH DESIGN AND METHODS: In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL (n = 2,518) or standard statin therapy targeting LDL-C 100-120 mg/dL (n = 2,524). RESULTS: Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group (P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67-1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31-0.88]; P = 0.01). Safety did not differ significantly between the two groups. CONCLUSIONS: We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation.

Add-on Antiplatelet Effects of Eicosapentaenoic Acid With Tailored Dose Setting in Patients on Dual Antiplatelet Therapy.

The aim of this study was to investigate the antiplatelet effects of eicosapentaenoic acid (EPA) at a sufficient dose following coronary stent implantation. Thirty-one patients on dual antiplatelet therapy with aspirin and clopidogrel were treated with highly purified EPA-E (Epadel®) for 12 weeks. Based on our previous study, patients with a high baseline EPA/arachidonic acid (AA) ratio (≥ 0.37; n = 11) were given a standard dose (1800 mg daily) of EPA-E, whereas those with a low EPA/AA ratio (< 0.37; n = 20) were given a high dose (2700 mg daily) to reach the target value of > 0.92. Platelet function was then evaluated with agonist-induced aggregation using light transmittance aggregometry and VerifyNow®. After EPA-E treatment, the EPA/AA ratio significantly increased from 0.28 to 1.31 (P < 0.001). Collagen (1, 2, and 4 µg/mL)-induced maximal platelet aggregation (MPA) was significantly suppressed after EPA-E administration (from 28.0 to 24.0, P = 0.033; from 44.0 to 40.0, P = 0.016; from 60.0 to 56.0, P = 0.010; respectively). However, there were no changes in MPA induced by adenosine diphosphate and AA and in P2Y12 reaction units (PRU) and aspirin reaction units. After EPA-E treatment, PRU was significantly suppressed in 8 patients showing high on-treatment platelet reactivity (HTPR) (baseline 305; 266-321 versus on-treatment 256; 233-261, P = 0.012), but not in those without HTPR (201; 156-220 versus 183; 159-233, P = 0.212). In conclusion, EPA treatment at a sufficient dose suppressed platelet aggregation and showed possible add-on effects in patients with clopidogrel hyporesponsiveness.

Duration of reverse remodeling response to cardiac resynchronization therapy: Rates, predictors, and clinical outcomes.

BACKGROUND: A subset of patients undergoing cardiac resynchronization therapy (CRT) for heart failure (HF) with severe left ventricular (LV) dysfunction experience only short-lived LV reverse remodeling. Little is known about the incidence and prognosis of this finding. We sought to identify predictors of a brief response and investigated the prognosis in a retrospective study. METHODS: A total of 528 patients from a Japanese multicenter database with full echocardiography datasets were enrolled. Follow-up was 3.4±1.3years. Based on relative reduction in LV end-systolic volume (LVESV) at 6months, we categorized patients as responders (reduction in LVESV ≥15%) and non-responders (NRs; reduction in LVESV <15%). Based on reduction in LVESV at 1-2years, responders were subdivided into long-lasting responders (reduction in LVESV ≥15%) and brief responders (reduction in LVESV <15%). RESULTS: Of 328 responders, 50 (15%) were brief responders. Predictors of brief response were prior ventricular tachyarrhythmia, a non-left bundle-branch block (LBBB) intrinsic QRS pattern, and prior hospitalization for HF. The risk of all-cause death in brief responders was significantly lower than that in NRs (P=0.034) and tended to be higher than that in long-lasting responders (P=0.080). CONCLUSIONS: Approximately 15% of responders were brief responders. Prior ventricular tachyarrhythmia, a non-LBBB pattern, and HF hospitalization were independent predictors of a brief response. Brief response was significantly associated with decreased risk of all-cause death compared with NRs and had a tendency toward increased risk of all-cause death compared with long-lasting responders.

Risk of bleeding and repeated bleeding events in prasugrel-treated patients: a review of data from the Japanese PRASFIT studies.

Prasugrel is a third-generation thienopyridine that achieves potent platelet inhibition with less pharmacological variability than other thienopyridines. However, clinical experience suggests that prasugrel may be associated with a higher risk of de novo and recurrent bleeding events compared with clopidogrel in Japanese patients undergoing percutaneous coronary intervention (PCI). In this review, we evaluate the risk of bleeding in Japanese patients treated with prasugrel at the doses (loading/maintenance doses: 20/3.75 mg) adjusted for Japanese patients, evaluate the risk factors for bleeding in Japanese patients, and examine whether patients with a bleeding event are at increased risk of recurrent bleeding. This review covers published data and new analyses of the PRASFIT (PRASugrel compared with clopidogrel For Japanese patIenTs) trials of patients undergoing PCI for acute coronary syndrome or elective reasons. The bleeding risk with prasugrel was similar to that observed with the standard dose of clopidogrel (300/75 mg), including when bleeding events were re-classified using the Bleeding Academic Research Consortium criteria. The pharmacodynamics of prasugrel was not associated with the risk of bleeding events. The main risk factors for bleeding events were female sex, low body weight, advanced age, and presence of diabetes mellitus. Use of a radial puncture site was associated with a lower risk of bleeding during PCI than a femoral puncture site. Finally, the frequency and severity of recurrent bleeding events during continued treatment were similar between prasugrel and clopidogrel. In summary, this review provides important insights into the risk and types of bleeding events in prasugrel-treated patients.Trial registration numbers: JapicCTI-101339 and JapicCTI-111550.

Preliminary report on a cost-utility analysis of revascularization by percutaneous coronary intervention for ischemic heart disease.

Few socioeconomic studies have so far reported on revascularization for stable ischemic heart disease in Japan. This study aimed to validate the sensitivity of the health-related quality of life (HRQOL) scale for determining the pathology and medical technology to be used and to validate the application of a cost-utility analysis model. We studied 32 patients who had undergone percutaneous coronary intervention (PCI) (mean age 67.9 ± 7.3 years). For HRQOL, utility and quality of life (QOL) were examined using the EuroQol 5 Dimension (EQ-5D) and EuroQol Visual Analogue Scale (EQ-VAS), respectively. The changes in the utility index before and after PCI were compared between the PCI and coronary angiography (CAG) groups to determine the sensitivity of the EQ-5D that was used to calculate quality-adjusted life years (QALY). Additionally, to estimate the cost-utility of PCI 120 months after the procedure, we analyzed our study results and the results of previous reports using the Markov chain model. The utility index was found to improve in the PCI group (0.08 ± 0.15), whereas it decreased in the CAG group (-0.02 ± 0.11) (p = 0.049). The estimated result of the cost-utility analysis as the increase in utility above baseline level was the expected value, that is, 70,000 US$/QALY. Our findings suggest that QALY may be valid as a utility index in the clinical and economic evaluation of PCI in Japan.

Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome　- Findings From the PACIFIC Registry.

BACKGROUND: Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients. METHODS AND RESULTS: The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, ß-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non-smoking status, blood pressure <130/80 mmHg, and 18.5≤body mass index≤24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age ≥75 years (P=0.004), HbA1c ≥7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post-discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004). CONCLUSIONS: Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients. (Circ J 2016; 80: 1607-1614).