Yuka Suzuki

Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts

BACKGROUND The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. OBJECTIVE The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. METHODS Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. CONCLUSION Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs.

Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy

Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

The East–West late lumen loss study: Comparison of angiographic late lumen loss between Eastern and Western drug-eluting stent study cohorts

Background Regulatory decisions approving new coronary drug‐eluting stent (DES) require mechanistic observations of angiographic late lumen loss (LLL). Patient safety and device approval times could be enhanced if angiographic follow‐up data were found to be generalizable across jurisdictions and geographies. The objectives were to assess the comparability of in‐segment LLL in Eastern and Western DES populations using the worlds largest compilation of follow‐up quantitative coronary angiography data. Methods Data from 4 manufacturers involving 29 DES clinical trials in Eastern and Western hemispheres were compiled. “East” and “West” cohorts were defined by trial location. Independent core laboratories quantified in‐segment LLL for all studies. East and West were compared before and after adjustment for clinical and anatomic covariates known to correlate with LLL via conditioning on propensity score quintiles. An international panel of experts and regulators prospectively established a clinically meaningful difference between East and West mean in‐segment LLL of ±0.40 mm. Results The data set comprised 2,047 East and 4,456 West patients. Unadjusted mean ± SD for West and East in‐segment LLL (mm) was 0.25 ± 0.46 and 0.12 ± 0.42, respectively (difference 0.13 mm; 95% CI 0.11‐0.16). Propensity score–adjusted in‐segment LLL East and West least squares means were 0.11 and 0.26 mm, respectively (difference 0.15 mm; 95% CI 0.13‐0.18). Conclusions In the worlds largest compilation of DES protocol 8‐ to 13‐month angiographic follow‐up data, clinically meaningful comparability of in‐segment LLL by independent core laboratory quantitative coronary angiography in East and West cohorts was demonstrated in both unadjusted and adjusted comparisons. These findings suggest that DES LLL, once characterized, could be generalized across regulatory jurisdictions over the course of global registration efforts.