Predictors of death or myocardial infarction, ischaemic-driven revascularisation, and major adverse cardiovascular events following everolimus-eluting or paclitaxel-eluting stent deployment: Pooled analysis from the SPIRIT II, III, IV and COMPARE trials

Aims: Although clinical trials have demonstrated superior clinical efficacy and improved safety of the everolimus-eluting stent (EES) compared with paclitaxel-eluting stents (PES) the clinical, angiographic and procedural factors associated with adverse clinical outcomes following drug-eluting stent (DES) deployment have not been carefully analysed. Methods and results: We performed a patient-level pooled database analysis from the SPIRIT II, III, IV and COMPARE prospective randomised (EES versus PES) trials which enrolled 6,789 patients undergoing coronary stenting with follow-up through two years. To determine independent predictors of death, myocar- dial infarction (MI), ischaemia-driven revascularisation (target lesion [ID-TLR] or target vessel [ID-TVR]), and major adverse cardiovascular events ([MACE]; composite occurrence of cardiovascular death, MI, ID-TLR), we analysed clinical, angiographic and procedural variables using Cox proportional hazard stepwise regression analysis. Treatment with EES (versus PES) was a powerful, independent predictor of relative freedom from MI (HR [95% CI]= 0.54 [0.41, 0.71]; p<0.0001), cardiac death or MI (0.63 [0.49, 0.80]; p=0.0002), ID-TLR (0.59 [0.47, 0.74]; p<0.0001), ID-TVR (0.70 [0.58,0.84]; p=0.0002) and MACE (0.64 [0.54, 0.77]; p<0.0001). Both diabetes and the extent of coronary artery disease as reflected by the number of lesions treated were predictive of cardiac death, ID-TLR, ID-TVR, MI and MACE. Conclusions: This multivariate analysis identified independent predictors of adverse outcomes to two years following DES deployment. Treatment with EES (versus PES) is an independent predictor of freedom from MI, cardiac death or MI, ID-TLR, ID-TVR and MACE

Stent thrombosis: Insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials

Aims: Recent studies have suggested that EES may reduce ST compared to PES, but no individual trial has been adequately powered for this endpoint. The incidence of stent thrombosis, as well as the impact of dual antiplatelet therapy (DAPT) discontinuation during the first two years following everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) deployment were therefore analysed from a pooled, patient-level database derived from four randomised clinical trials. Methods and results: Data from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials (n=6,789 patients) were analysed. Two-year ST rates were determined using time-to-event methods and compared with the log-rank test. ST rates were also determi

Clinical, Angiographic, and Procedural Correlates of Acute, Subacute, and Late Absorb Scaffold Thrombosis

OBJECTIVES: The authors sought to identify and verify independent correlates of device thrombosis from an analysis of multicenter trials and registries. BACKGROUND: Recent analyses suggest an increased risk of device thrombosis with Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) implantation compared with metallic drug-eluting stents, and data from moderate size studies suggest a risk relationship to vessel size and technique. METHODS: From 8,771 consecutively treated patients, 105 patients (1.2%) were identified with scaffold thrombosis within 1 year of implantation. They were matched 2:1 with controls selected randomly from nonthrombosis patients. Data-restricted multiple logistic analysis was used to identify significant independent covariates of the outcome. RESULTS: Early (within 1 month) scaffold thrombosis occurred in 69 patients and late (1 to 12 months) thrombosis occurred in 36 patients. Modelling found significant correlations of thrombosis to be final minimal lumen diameter 1.1:1 balloon/scaffold ratio (OR: 2.3; p = 0.022), and reference vessel diameter <2.40 mm (OR: 2.1; p = 0.036). CONCLUSIONS: Suboptimal vessel sizing, procedural technique, angiographic outcomes, and dual antiplatelet therapy discontinuation appear to be the principal determinants of Absorb scaffold thrombosis risk through 12 months after implantation

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): A randomized, placebo-controlled, double-blinded trial

Aims Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) &lt;_45% and LV results scar size &gt;_15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. © 2020 Oxford University Press. All rights reserved

Clinical, Angiographic, and Procedural Correlates of Very Late Absorb Scaffold Thrombosis: Multistudy Registry Results

OBJECTIVES: The aim of this study was to identify independent correlates of very late scaffold thrombosis (VLST) from an analysis of consecutively treated patients from 15 multicenter studies. BACKGROUND: Recent analyses suggest an increased risk for VLST with the Absorb Bioresorbable Vascular Scaffold compared with drug-eluting stents, but insights as to correlates of risk are limited. METHODS: A total of 55 patients were identified with scaffold thrombosis. They were matched 2:1 with control subjects selected randomly from patients without thrombosis from the same study. Quantitative coronary angiography was available for 96.4% of patients. Multiple logistic and Cox regression analysis were used to identify significant independent outcome correlates from 6 pre-specified characteristics. RESULTS: Patients had scaffold thrombosis at a median of 20 months (interquartile range: 17 to 27 months). Control subjects were followed for 36 months (interquartile range: 24 to 38 months). For the combined groups, reference vessel diameter (RVD) was 2.84 +/- 0.50 mm, scaffold length was 26 +/- 16 mm, and post-dilatation was performed in 56%. Univariate correlates of thrombosis were smaller nominal scaffold/RVD ratio (linear p = 0.001; ratio 2.72 mm; odds ratio: 3.4; p = 0.001). Post-dilatation at >/=16 atm, post-dilatation balloon/scaffold ratio, final percentage stenosis, and dual antiplatelet therapy were not correlated with VLST. Only scaffold/RVD ratio remained a significant independent correlate of VLST (p = 0.001), as smaller ratio was correlated with RVD (p < 0.001). Post hoc analysis of 8 other potential covariates revealed no other correlates of outcome. CONCLUSIONS: In the present analysis, the largest to date of its type, relative scaffold undersizing was the strongest determinant of VLST. Given current understanding of "scaffold dismantling," this finding likely has ramifications for all bioresorbable scaffolds