Prasugrel for Japanese Patients With Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II)　- Final 2-Year Follow-up Results of a Postmarketing Observational Study.

BACKGROUND: PRASFIT-Practice II is a postmarketing observational study conducted in 4,155 Japanese patients with ischemic heart disease (IHD) who received long-term prasugrel. The data were used to assess the utility of Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria.Methods and Results:Patients in PRASFIT-practice II were clinically followed for 2 years. The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding. Patients were divided into 2 groups based on ARC-HBR criteria (HBR (40.1% of patients) and non-HBR (59.9%)) and the effect of HBR on the primary endpoint was assessed. The median duration of dual antiplatelet therapy with prasugrel was 391.0 days. At 2 years, the cumulative incidence of MACE was 3.3%, and of TIMI major/minor bleeding was 2.7%. At 1 year, MACE and TIMI major/minor bleeding in the HBR group (4.0% and 3.4%, respectively) were higher than that in the non-HBR group (1.3% for both). Landmark analysis at 3 months and 1 year showed that the higher risk of MACE or TIMI major/minor bleeding in the HBR group persisted through 2 years. CONCLUSIONS: The results of this study confirmed the safety and effectiveness of long-term treatment with prasugrel, and demonstrated that the ARC-HBR criteria for bleeding risk are applicable in Japanese IHD patients treated with prasugrel.

Prasugrel for Japanese Patients With Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II)　- 1-Year Follow-up Results of a Postmarketing Observational Study.

BACKGROUND: Although the effectiveness and safety of prasugrel for the prevention of cardiovascular events in patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) have been demonstrated, long-term real-world data of Japanese unique doses are insufficient. Therefore, we report the results of an analysis of 1-year follow-up data from a postmarketing observational study (PRASFIT-Practice II).Methods and Results:The safety and effectiveness analysis sets included 4,155 IHD patients receiving prasugrel (loading dose/maintenance dose, 20/3.75 mg) as dual antiplatelet therapy (DAPT) with aspirin. At 360 days (after treatment start), 62.2% continued DAPT. Cumulative incidences of major adverse cardiovascular events and stent thrombosis were 1.6% and 0.2%, respectively. Cumulative incidences of Thrombolysis In Myocardial Infarction (TIMI) major bleeding and TIMI major or minor bleeding were 1.0% and 2.0%, respectively. Risk factors for TIMI major or minor bleeding in the first 30 days of treatment were age ≥80 years, anemia, female sex, and liver disease, and from day 31 to the end of month 12, hypertension and peptic ulcer. CONCLUSIONS: The 1-year follow-up results showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of IHD patients undergoing PCI.

Prasugrel for Japanese Patients With Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II)　- A 3-Month Interim Analysis of a Postmarketing Observational Study.

BACKGROUND: A unique dose of prasugrel has been approved exclusively for Japanese patients, but real-world data for prasugrel at that dose in patients with ischemic heart disease (IHD) are limited. Therefore, large-scale, real-world data are needed. Methods and Results: A 2-year observational study of Japanese patients with IHD undergoing percutaneous coronary intervention and being treated with prasugrel to evaluate safety and effectiveness. This report is an interim analysis of data from case report forms (CRFs) after 3 months. CRFs were collected from 4,270 patients, 4,157 of whom were eligible for the safety and effectiveness analysis sets (mean age, 68.3 years; male, 76.5%). The median treatment period was 112 days, and 92.3% of patients continued treatment with prasugrel. The incidence of non-coronary artery bypass grafting-related bleeding adverse events (AEs) was 3.1%, of which Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding accounted for 0.5% and 0.6%, respectively. The most common bleeding AEs were gastrointestinal disorders, which accounted for 43.2% of the sum of "TIMI major and minor bleeding AEs". The incidence of major adverse cardiovascular events (MACE) was 1.0%, and the cumulative incidence of MACE was 1.4%. The incidence of stent thrombosis was 0.2%. CONCLUSIONS: Interim study results indicated that prasugrel was safe and effective during the early phase of treatment in Japanese patients with IHD in real-world clinical settings.

[Protection of human subjects in medical research: from the viewpoint of historical development of ethical regulations].

Recent clinical research is conducted based on bioethical consideration of human subjects. The Ethical Guidelines for Clinical Studies (EGCS) form the standard for this 'subject protection'. In current clinical research, consideration of subject rights and life is held more important than the scientific and social value of the research. We describe herein the major revisions and history of ethical considerations leading up to implementation of the revised EGCS on April 1, 2009. The obligations of clinical researchers regarding ethical studies and training and enrollment in insurance for subject compensation have been added to these latest guidelines. The role of ethics review boards, which supervise whether clinical researchers are actively performing subject protection, is also becoming extremely important.

Bleeding risks associated with anticoagulant therapies after percutaneous coronary intervention in Japanese patients with ischemic heart disease complicated by atrial fibrillation: A comparative study.

BACKGROUND: Current guidelines recommend early termination of triple therapy and the use of direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) patients who undergo percutaneous coronary intervention (PCI), due to safety concerns. However, to date, real-world medication usage and safety outcomes (specifically bleeding) in NVAF patients with stent implantation have not been well assessed. METHODS: This was a retrospective, observational, medical database cohort study in Japanese ischemic heart disease (IHD) patients with NVAF who underwent PCI between 2012 and 2017. The primary outcome was clinically relevant bleeding; secondary outcomes included individual bleeding events. A multivariate analysis was conducted to identify risk factors affecting the occurrence of clinically relevant bleeding events. RESULTS: The analysis population comprised 5695 patients [3530 received DOACs and 2165 received vitamin K antagonists (VKAs)]. The incidence of primary outcome events (clinically relevant bleeding/100 patient-years) was 6.05 in the DOAC group and 8.42 in the VKA group, resulting in a nonsignificant 21% lower risk in the DOAC group. The DOAC group also had a nonsignificant 24%, 24%, and 34% lower risk of bleeding requiring transfusion, intracranial bleeding, and lower gastrointestinal bleeding, respectively, compared with the VKA group. A multivariate analysis of the primary outcome showed a significantly higher risk of bleeding among older patients and those with lower body weight and abnormal renal function. CONCLUSIONS: In this retrospective real-world evaluation of IHD patients with NVAF and PCI, DOAC-treated patients had a lower risk of developing clinically relevant bleeding compared with the VKA group.

IgA-associated glomerulonephritis with membranoproliferative glomerulonephritis-like pattern in two children.

In this article, we report two patients with IgA-associated glomerulonephritis with a membranoproliferative glomerulonephritis (MPGN) -like pattern. Both patients had nephrotic syndrome at onset. One patient was treated with high-dose alternate-day prednisolone (PSL), and the other with indomethacin and low-dose PSL. One lost the urinary abnormalities 3 years after starting treatment. The other lost the nephrotic state and hematuria over a 5-year period, but proteinuria persisted until the last follow-up. Both patients had diffuse proliferative changes with mesangial interposition and subendothelial deposits, associated with strongly positive deposits of C3 and IgA along the capillary walls of the glomeruli. These two patients showed histological changes compatible with type-I MPGN, but the pattern of IgA deposits was not typical of idiopathic MPGN or IgA nephropathy. We assume this is a rare form of MPGN, not associated with liver disease or other systemic diseases.