Prospective randomized comparison of clinical and angiographic outcomes between everolimus-eluting vs. zotarolimus-eluting stents for treatment of coronary restenosis in drug-eluting stents: intravascular ultrasound volumetric analysis (RESTENT-ISR trial)

Hong, Soon Jun,Ahn, Chul Min,Kim, Byeong-Keuk,Ko, Young-Guk,Hur, Seung-Ho,Yu, Cheol Woong,Lee, Seung-Jin,Choi, Cheol Ung,Kim, Je Sang,Yoon, Jung-Han,Hong, Young Joon,Choi, Jae-Woong,Choi, Seung-Hyuk,J The European Society of Cardiology 2016 European heart journal Vol.37 No.45

<P><B>Aims</B></P><P>At present no proven standard treatment for drug-eluting stent (DES) restenosis is available, and the efficacy and safety of everolimus-eluting stent (EES) and zotarolimus-eluting stent (ZES) for DES restenosis are limited. The purpose of this prospective, randomized 9-month intracoronary ultrasound (IVUS) and 3-year clinical follow-up study was to compare the effects of EESs and ZESs on neointima volume and major adverse cardiovascular events (MACEs) such as death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis in DES restenosis patients.</P><P><B>Methods and results</B></P><P>Patients were eligible for this study if they were between 40 and 75 years old with in-stent restenosis >50% by quantitative coronary angiographic analysis in DES or within 5 mm of the stent edges with signs of ischaemia. Eligible patients (<I>n</I> = 304, 146 women and 158 men) were randomly assigned to receive either EES (158 patients) or ZES (146 patients). The primary endpoint of the study was to compare neointima volume between the EES and ZES groups at the 9-month follow-up IVUS. MACEs, including death, non-fatal MI, stent thrombosis and the need for repeated TLR within 3 years, were noted. The 9-month angiographic and IVUS follow-up showed no significant differences in late lumen loss (0.40 ± 0.56 vs. 0.45 ± 0.61 mm, <I>P</I> = 0.57, respectively) and neointima volume (0.51 ± 0.48 vs. 0.56 ± 0.54 mm<SUP>3</SUP>/1 mm, <I>P</I> = 0.47, respectively) in the EES and the ZES groups. Composite MACEs such as death, MI, stent thrombosis and TLR during 3-year follow-up were comparable between the two groups [15.8% (<I>n</I> = 25) in the EES group and 22.6% (<I>n</I> = 33) in the ZES group, <I>P</I> = 0.276], independent of <I>de novo</I> DES type, sex, age, body mass index, presence of diabetes, hypertension and dyslipidaemia.</P><P><B>Conclusions</B></P><P>Patients with first- and second-generation DES restenosis, both EES and ZES implantation were effective and safe in reducing neointima volume and late loss with a comparable rate of MACEs independent of cardiovascular risk factors. </P>

Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis

Kang, Si-Hyuck,Park, Kyung Woo,Kang, Do-Yoon,Lim, Woo-Hyun,Park, Kyung Taek,Han, Jung-Kyu,Kang, Hyun-Jae,Koo, Bon-Kwon,Oh, Byung-Hee,Park, Young-Bae,Kandzari, David E.,Cohen, David J.,Hwang, Seung-Sik The European Society of Cardiology 2014 European heart journal Vol.35 No.17

<P><B>Background</B></P><P>The aim of this study was to compare the safety and efficacy of biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS), and durable-polymer DES in patients undergoing coronary revascularization, we performed a systematic review and network meta-analysis using a Bayesian framework.</P><P><B>Methods and results</B></P><P>Study stents included BMS, paclitaxel-eluting (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt–chromium everolimus-eluting (CoCr-EES), platinium–chromium everolimus-eluting (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients were selected. The principal endpoint was definite or probable stent thrombosis (ST) defined according to the Academic Research Consortium within 1 year.</P><P><B>Results</B></P><P>Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible interval (CrI), 0.33–0.90], SES (OR, 0.53; 95% CrI, 0.38–0.73), CoCr-EES (OR, 0.34; 95% CrI, 0.23–0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10–0.90) were all superior to BMS in terms of definite or probable ST within 1 year. Cobalt–chromium everolimus-eluting stents demonstrated the lowest risk of ST of all stents at all times after stent implantation. Biodegradable polymer-biolimus-eluting stents was associated with a higher risk of definite or probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04–2.98). All DES reduced the need for repeat revascularization, and all but PES reduced the risk of myocardial infarction compared with BMS.</P><P><B>Conclusions</B></P><P>All DESs but PES and ZES-E were superior to BMS in terms of ST within 1 year. Cobalt–chromium everolimus-eluting stents was safer than any DES even including BP-BES. Our results suggest that not only the biodegradability of polymer, but the optimal combination of stent alloy, design, strut thickness, polymer, and drug all combined determine the safety of DES.</P>

Peroxisome proliferator-activated receptor-δ activates endothelial progenitor cells to induce angio-myogenesis through matrix metallo-proteinase-9-mediated insulin-like growth factor-1 paracrine networks

Han, Jung-Kyu,Kim, Hack-Lyoung,Jeon, Ki-Hyun,Choi, Young-Eun,Lee, Hyun-Sook,Kwon, Yoo-Wook,Jang, Ja-June,Cho, Hyun-Jai,Kang, Hyun-Jae,Oh, Byung-Hee,Park, Young-Bae,Kim, Hyo-Soo The European Society of Cardiology 2013 European heart journal Vol.34 No.23

<P><B>Aims</B></P><P>The roles of peroxisome proliferator-activated receptor (PPAR)-δ in vascular biology are mainly unknown. We investigated the effects of PPAR<B>-δ</B> activation on the paracrine networks between endothelial progenitor cells (EPCs) and endothelial cells (ECs)/skeletal muscle.</P><P><B>Methods and results</B></P><P>Treatment of EPCs with GW501516, a PPAR-<B>δ</B> agonist, induced specifically matrix metallo-proteinase (MMP)-9 by direct transcriptional activation. Subsequently, this increased-MMP-9 broke down insulin-like growth factor-binding protein (IGFBP)-3, resulting in IGF-1 receptor (IGF-1R) activation in surrounding target cells. Treatment of conditioned medium from GW501516-stimulated EPCs enhanced the number and functions of human umbilical vein ECs and C2C12 myoblasts via MMP-9-mediated IGF-1R activation. Systemic administration of GW501516 in mice increased MMP-9 expression in EPCs, and augmented IGFBP-3 degradation in serum. In a mouse hindlimb ischaemia model, systemic treatment of GW501516 or local transplantation of GW501516-treated EPCs induced IGF-1R phosphorylation in ECs and skeletal muscle in the ischaemic limbs, leading to augmented angiogenesis and skeletal muscle regeneration. It also enhanced wound healing with increased angiogenesis in a mouse skin punch wound model. These pro-angiogenic and muscle-regenerating effects were abolished by MMP-9 knock-out.</P><P><B>Conclusion</B></P><P>Our results suggest that PPAR-<B>δ</B> is a crucial modulator of angio-myogenesis via the paracrine effects of EPCs, and its agonist is a good candidate as a therapeutic drug for patients with peripheral vascular diseases.</P>

Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) S

Cho, Iksung,Chang, Hyuk-Jae,Ó,Hartaigh, Brí,ain,Shin, Sanghoon,Sung, Ji Min,Lin, Fay Y.,Achenbach, Stephan,Heo, Ran,Berman, Daniel S.,Budoff, Matthew J.,Callister, Tracy Q.,Al-Mallah, Moua The European Society of Cardiology 2015 European heart journal Vol.36 No.8

<P><B>Aim</B></P><P>Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown.</P><P><B>Methods and results</B></P><P>From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0–10, 11–100, 101–400, 401–1000, >1000. For CCTA analysis, the number of obstructive vessels—as defined by the per-patient presence of a ≥50% luminal stenosis—was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) <I>χ</I><SUP>2</SUP>, <I>C</I>-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th–75th percentile, 17–30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LR<I>χ</I><SUP>2</SUP>, 25.34; increment in <I>C</I>-statistic, 0.24; NRI, 0.62, all <I>P</I> < 0.001), but not among those with CACS ≤100 (all <I>P</I> > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS.</P><P><B>Conclusion</B></P><P>Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.</P>

Frequency, causes, predictors, and clinical significance of peri-procedural myocardial infarction following percutaneous coronary intervention

Park, Duk-Woo,Kim, Young-Hak,Yun, Sung-Cheol,Ahn, Jung-Min,Lee, Jong-Young,Kim, Won-Jang,Kang, Soo-Jin,Lee, Seung-Whan,Lee, Cheol Whan,Park, Seong-Wook,Park, Seung-Jung The European Society of Cardiology 2013 European heart journal Vol.34 No.22

<P><B>Aims</B></P><P>Peri-procedural myocardial infarction (MI) is a not infrequent complication of percutaneous coronary intervention (PCI), but conflicting information exists regarding incidence and prognostic impact of this event. We investigated frequency, causes, predictors, and clinical relevance of peri-procedural MI, using a large database.</P><P><B>Methods and results</B></P><P>We pooled individual patient-level data from 11 PCI studies in which peri-procedural creatine kinase-MB mass was routinely measured and mortality data were prospectively collected. Among 23 604 patients from 11 studies, 1677 {7.1% [95% confidence interval (CI) 6.8–7.5%]} had peri-procedural MI. The most common mechanism of peri-procedural MI was side-branch occlusion. Independent predictors of peri-procedural MI were older age, female gender, diabetes, hypertension, renal dysfunction, multivessel disease, left anterior descending artery disease, left main disease, bifurcation lesion, long lesion, drug-eluting stents, and number of stents. Follow-up varied from 1 year to 5 years. In a crude analysis, patients with peri-procedural MI had significantly a higher risk of mortality than those without peri-procedural MI [hazard ratio (HR) 1.47; 95% CI 1.24–1.74]. After adjustment for baseline covariates, peri-procedural MI was associated with an increased risk of mortality (HR 1.20; 95% CI 1.04–1.39).</P><P><B>Conclusion</B></P><P>Among patients undergoing PCI, the occurrence of peri-procedural MI measured by CK-MB mass assay was ∼7%, and more than half of cases were associated with side-branch occlusion. Several higher risk patients, lesions, and procedural characteristics were independent predictors of peri-procedural MI. Peri-procedural MI was associated with an increase in mortality.</P>

Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent

Park, Jun-Bean,Kang, Do-yoon,Yang, Han-Mo,Cho, Hyun-Jai,Park, Kyung Woo,Lee, Hae-Young,Kang, Hyun-Jae,Koo, Bon-Kwon,Kim, Hyo-Soo The European Society of Cardiology 2013 European heart journal Vol.34 No.12

<P><B>Aims</B></P><P>The association between alkaline phosphatase (ALP) and mortality was reported in several subgroups of patients. But, the role of ALP in overall coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to examine the prognostic value of the ALP level in patients with CAD who underwent PCI with drug-eluting stent (DES).</P><P><B>Methods and results</B></P><P>We prospectively included CAD patients who underwent PCI with DES. After exclusion of patients with liver disease and cancer, 1636 patients were selected for the analysis of clinical outcomes (median duration of follow-up; 762 days, inter-quartile range; 494–1068 days), and were classified into tertiles by baseline measurements of ALP (<63, 63–78, and >78 IU/L). After adjustment of potential confounders including angiographic data, the independent and dose-dependent association was observed between tertile of ALP and the adjusted hazard ratio (HR) of all-cause mortality (<I>P</I> for trend < 0.0001). Specifically, compared with the lowest ALP tertile, the adjusted HR of all-cause mortality in the highest tertile was 4.21 (95% confidence interval 2.03–8.71). In subgroup of patients with stable or unstable angina, a similar association was noted (<I>P</I> for trend < 0.0001). In terms of cardiovascular mortality, myocardial infarction, and stent thrombosis, the adjusted HRs in the highest ALP tertile were 3.92 (1.37–11.20), 1.98 (0.91–4.29), and 2.73 (1.33–5.61), respectively, compared with the lowest tertile. Furthermore, evaluation of both ALP and C-reactive protein provided better predictive value than either alone. Interesting result suggesting the mechanism was that ALP was significantly associated with the presence of angiographic coronary calcification (<I>P</I> for trend = 0.046).</P><P><B>Conclusion</B></P><P>Our study demonstrated that the higher serum ALP level is an independent predictor of mortality, myocardial infarction, and stent thrombosis in CAD patients after PCI with DES.</P>