Cilostazol combined with P2Y12 receptor inhibitors: A substitute antiplatelet regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation.

BACKGROUND: Cilostazol combined with P2Y12 receptor inhibitor has been used as a substitute regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation on a small scale. Its exact impact on platelet functions and clinical benefits of aspirin-intolerant patients is unknown. HYPOTHESIS: Cilostazol combined with P2Y12 receptor inhibitors could be used as a substitute antiplatelet regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation. METHODS: In this multicenter prospective cohort trial, patients undergoing elective percutaneous coronary stent implantation were assigned to the cilostazol group (cilostazol plus P2Y12 receptor inhibitors), based on aspirin intolerance criteria, or the aspirin group (aspirin plus P2Y12 receptor inhibitors). Platelet PAC-1, CD62p, and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) were detected by flow cytometry. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, acute myocardial infarction, emerging arrhythmia, nonfatal stroke, and heart failure. The secondary endpoints were the Bleeding Academic Research Consortium (BARC) bleeding events. RESULTS: One hundred and fifty-four aspirin-intolerant percutaneous coronary stent implantation patients and 154 matched aspirin-tolerant patients from a total of 2059 percutaneous coronary stent implantation patients were enrolled. The relative activation level of PAC-1, CD62p, and platelet reaction index reflected by the VASP-P test were similar in the two groups (p > .05). After 12 months of follow-up, the incidence of all-cause death was 1.9% in the cilostazol group and 1.3% in the aspirin group (risk ratio [RR], 1.500; 95% confidence interval [CI], 0.254-8.852; p = 1.000); the incidence of acute myocardial infarction was 0.6% in the cilostazol group and 1.3% in the aspirin group (RR, 0.500; 95% CI, 0.046-5.457; p = 1.000). No significant difference was seen in other MACCE events, or in any types of BARC bleeding events. CONCLUSIONS: Cilostazol combined with P2Y12 inhibitors was not inferior to aspirin-based standard therapy and could be used as a reasonable substitute antiplatelet regimen for aspirin-intolerant patients undergoing percutaneous coronary stent implantation, but again with limitations, which required a larger sample and longer follow-up to confirm its efficacy.

Bcl-2 Is Involved in Cardiac Hypertrophy through PI3K-Akt Pathway.

Cardiac hypertrophy (CH) is a common cause of sudden cardiac death and heart failure, resulting in a significant medical burden. The present study is aimed at exploring potential CH-related pathways and the key downstream effectors. The gene expression profile of GSE129090 was obtained from the Gene Expression Omnibus database (GEO), and 1325 differentially expressed genes (DEGs) were identified, including 785 upregulated genes and 540 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway enrichment analysis of DEGs were then performed. Although there were no pathways enriched by downregulated genes, many CH-related pathways were identified by upregulated genes, including PI3K-Akt signaling pathway, extracellular matrix- (ECM-) receptor interaction, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy (HCM). In the deeper analysis of PI3K-Akt signaling pathway, we found all the signaling transduction pointed to B cell lymphoma-2- (Bcl-2-) mediated cell survival. We then demonstrated that PI3K-Akt signaling pathway was indeed activated in cardiac hypertrophy. Furthermore, no matter LY294002, an inhibitor of the PI3K/AKT signaling pathway, or Venetoclax, a selective Bcl-2 inhibitor, protected against cardiac hypertrophy. In conclusion, these data indicate that Bcl-2 is involved in cardiac hypertrophy as a key downstream effector of PI3K-Akt signaling pathway, suggesting a potential therapeutic target for the clinical management of cardiac hypertrophy.

A stricter control of low-density lipoprotein is necessary for thrombosis reduction in "lower thrombosis risk" patients with atrial fibrillation: a multicenter retrospective cohort study.

Patients with atrial fibrillation (AF) are associated with increased thrombotic events. Our previous case-control study showed low-density lipoprotein cholesterol (LDL-C) was an independent predictor of ischemic stroke in AF patients. To investigate the risks of thrombosis in relation to LDL-C among AF patients at different stroke risks by long-time follow-up. Atrial fibrillation patients without history of thrombosis enrolled from five hospitals were classified into low-risk (LR) and high-risk (HR) group according to CHA2DS2VASc score and followed up with a median period of 26 months. Univariate and multivariate logistic regression analysis were performed in each group. The best cut-off value calculated by receiver operating characteristic (ROC) analysis was used to divide patients into low LDL-C (L-LDL) and high LDL-C (H-LDL) subgroups. Propensity score matching (PSM) and inverse probability of treatment weighted (IPTW) were utilized in both subgroups, after which Kaplan-Meier curves for thrombosis were performed. Univariate and multivariate analysis showed LDL-C was significantly related to thrombosis in LR, but less significantly in HR group. The best cut-off value was 2.155 mmol/L in LR and 2.795 mmol/L in HR group. Lower LDL-C was associated with decreased thrombosis in both groups by PSM and IPTW. Kaplan-Meier curves displayed that H-LDL subgroup was at higher thrombosis risk with significant difference at 24th month in LR patients. LDL-C independently predicts thrombosis with different cut-off values in AF patients at different risks. A stricter control of LDL-C level is necessary for thrombosis reduction in patients with lower score.