Safety and efficacy of PCSK9 inhibitor (evolocumab) in patients with non-ST segment elevation acute coronary syndrome and non-culprit artery critical lesions: a randomised controlled trial protocol (SPECIAL study).

INTRODUCTION: Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis <50%. Whether the application of PCSK9 inhibitors in patients with NSTE-ACS with non-culprit artery critical lesions (stenosis degree between 50% and 75%) has a similar effect on plaque regression and improvement of cardiovascular outcomes remains unknown, with a lack of relevant research. This study aims to further investigate the safety and efficacy of evolocumab in patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%). METHODS AND ANALYSIS: In this single-centre clinical randomised controlled trial, 122 patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%) will be randomly assigned to either the evolocumab treatment group or the standard treatment group after completing culprit vessel revascularisation. The evolocumab treatment group will receive evolocumab in addition to statin therapy, while the standard treatment group will receive standard statin therapy. At baseline and week 50, patients in the evolocumab treatment group will undergo coronary angiography and OCT imaging to visualise pre-existing non-lesional vessels. The primary end point is the absolute change in average minimum fibrous cap thickness (FCT) from baseline to week 50. Secondary end points include changes in plaque lipid arc, lipid length, macrophage grading, lipid levels and major adverse cardiovascular events during the 1-year follow-up period. ETHICS AND DISSEMINATION: Ethics: this study will adhere to the principles outlined in the Helsinki Declaration and other applicable ethical guidelines. This study protocol has received approval from the Medical Research Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), with approval number 2022-ky214. DISSEMINATION: we plan to disseminate the findings of this study through various channels. This includes publication in peer-reviewed academic journals, presentation at relevant academic conferences and communication to the public, policymakers and healthcare professionals. We will also share updates on the research progress through social media and other online platforms to facilitate the exchange and application of scientific knowledge. Efforts will be made to ensure widespread dissemination of the research results and to have a positive impact on society. TRIAL REGISTRATION NUMBER: ChiCTR2200066675.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen].

OBJECTIVE: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML). METHODS: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared. RESULTS: The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups. CONCLUSION: Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.