BACKGROUNDStudies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up.

METHODSThe SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up.

RESULTSDAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment.

CONCLUSIONSProlonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Adolescent ; Adult ; Aged ; Aspirin ; therapeutic use ; Drug-Eluting Stents ; Everolimus ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Prospective Studies ; Sirolimus ; analogs & derivatives ; therapeutic use ; Thrombosis ; drug therapy ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Young Adult

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast cancer. Therefore, anti-cancer treatment targeting key molecules in this signaling pathway has become research hot-spot in recent years. Randomized clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer, especially to those with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. Alpelisib, a PI3K inhibitor, and everolimus, an mTOR inhibitor, have been approved by Food and Drug Administration. Based on their high efficacy and relatively good safety profile, expanded indication of everolimus in breast cancer have been approved by National Medical Products Administration. Alpelisib is expected to be approved in China in the near future. The members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer, efficacy and clinical applications of PI3K/AKT/mTOR inhibitors, management of adverse reactions, and PIK3CA mutation detection, in order to promote the understanding of PI3K/AKT/mTOR inhibitors for Chinese oncologists, improve clinical decision-making, and prolong the survival of target patient population.
Breast Neoplasms/metabolism* ; Consensus ; Everolimus/therapeutic use* ; Female ; Humans ; MTOR Inhibitors ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Phosphoinositide-3 Kinase Inhibitors ; Proto-Oncogene Proteins c-akt/metabolism* ; Sirolimus/therapeutic use* ; TOR Serine-Threonine Kinases/metabolism*

INTRODUCTIONEverolimus eluting stents (EES) have demonstrated excellent re-stenosis and thrombosis rates in a number of randomised controlled trials. This study reported the real world experience in a single tertiary centre with EES in predominantly acute coronary syndrome (ACS) patients and compared the outcomes in small and large vessels. We measured the medium to long-term major adverse cardiovascular events (MACE) defined as all-cause mortality, myocardial infarction (MI) and target vessel revascularisation (TVR) and stent thrombosis.

MATERIALS AND METHODSAll consecutive patients underwent percutaneous coronary intervention (PCI) with EES (PROMUSTM, Boston Scientific, Natick USA; XIENCE VTM, Abbott Vascular, Santa Clara USA) between March 2007 and September 2009 recorded in our coronary intervention registry were included in this study. All patients were advised to stay on dual antiplatelet therapy with Aspirin 100 mg/day and Clopidogrel 75 mg/day. All patients had at least 6 months of clopidogrel, government funded and a further 6 months required self funding.

RESULTSFour hundred and six consecutive patients received EES during the study period; 403 were included in this study and 3 were lost to follow-up. Indications for PCI were stable angina in 11% of the patients, unstable angina in 38%, non-ST elevation myocardial infarction in 43%, and ST-elevation myocardial infarction in 8%. Procedural success was achieved in 99.5% of the cases. During a median follow-up of 23 months, 3% of the patients had an MI, 3% underwent TVR, 5% all-cause mortality and 2 (0.5%) cases of definite or probable stent thrombosis. The Kaplan Meier 2-year survival and MACE free survival were 95% and 89% respectively. A subgroup analysis comparing MACE in patients who were treated with a single small (≤ 2.75 mm; n = 91) or large (≥ 3 mm; n = 118). EES did not show significant difference during the 2-year follow-up (12% vs 9%; P = 0.34).

CONCLUSIONEverolimus eluting stent appears to be safe in a real world setting with satisfactory median-term outcomes which include low rates of TVR and other adverse events. EES appear to be equally effective in both small and large vessels.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; methods ; Aspirin ; therapeutic use ; Coronary Artery Disease ; drug therapy ; mortality ; therapy ; Drug-Eluting Stents ; Everolimus ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; New Zealand ; Platelet Aggregation Inhibitors ; therapeutic use ; Registries ; Retrospective Studies ; Sirolimus ; administration & dosage ; analogs & derivatives ; therapeutic use ; Survival Analysis ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Time Factors ; Treatment Outcome

BACKGROUNDEverolimus, a derivative of sirolimus, is a potent immunosuppressant that has important anti-proliferative properties. In the present study, we demonstrated the inhibiting neointimal hyperplasia in injured carotid arteries in rats by using two different doses of everolimus administrated via the oral route for a long time.

METHODSA rat model of carotid artery injury was established by balloon inflation. Eighty rats were randomly divided into the sham-operated group (n = 20), injury group (n = 20), low dosage of everolimus group (n = 20), and high dosage of everolimus group (n = 20). The low dose of everolimus (1.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 0.75 mg/kg per day for 28 days via intragastric gavage. High dose everolimus (2.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 1 mg/kg per day for 28 days. Expression of eukaryotic translation initiation factor 4E (eIF-4E) and phosphorylation of ribosomal protein S6 kinase 1 (P70S6K) were determined by reverse transcription-polymerase chain reaction and Western blotting analysis.

RESULTSIn the injured carotid artery, neointimal hyperplasia was normally observed four weeks after injury. Everolimus inhibited neointimal hyperplasia after balloon injury in a dose dependent manner. At the same time, the study demonstrated that everolimus reduced the expression of P-P70S6K, eIF-4E, transforming growth factor (TGF)-β1 and of proliferating cell nuclear antigen (PCNA).

CONCLUSIONSEverolimus significantly inhibited neointimal hyperplasia of the injured carotid artery. The effect depended on dosage and was associated with the reduction of phosphorylation of P70S6K and the eIF-4E expression level.

Animals ; Carotid Arteries ; drug effects ; Carotid Artery Injuries ; drug therapy ; Carrier Proteins ; metabolism ; Everolimus ; Male ; Neointima ; drug therapy ; Phosphoproteins ; metabolism ; Phosphorylation ; drug effects ; Rats ; Rats, Sprague-Dawley ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Sirolimus ; analogs & derivatives ; therapeutic use