Thin Strut CoCr biodegradable polymer biolimus A9-eluting stents versus thicker strut stainless steel biodegradable polymer Biolimus A9-eluting stents: Two-year clinical outcomes

© 2021 The Authors. Published by Hindawi. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1155/2021/6654515Background. While thinner struts are associated with improved clinical outcomes in bare-metal stents (BMS), reducing strut thickness may affect drug delivery from drug-eluting stents (DES) and there are limited data comparing otherwise similar thin and thick strut DES. We assessed 2-year outcomes of patients treated with a thin strut (84-88um) cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) and compared these to patients treated with a stainless steel, biodegradable polymer, Biolimus A9-eluting stent (SS-BP-BES). Methods. In total, 1257 patients were studied: 400 patients from 12 centres receiving ≥1 CoCr-BP-BES in the prospective Biomatrix Alpha registry underwent prespecified comparison with 857 patients who received ≥1 Biomatrix Flex SS-BP-BES in the LEADERS study (historical control). The primary outcome was major adverse cardiac events (MACE)-cardiac death, myocardial infarction (MI), or clinically driven target vessel revascularization (cd-TVR). Propensity analysis was used to adjust for differences in baseline variables and a landmark analysis at day-3 to account for differences in periprocedural MI definitions. Results. MACE at 2 years occurred in 6.65% CoCr-BP-BES versus 13.23% SS-BP-BES groups (unadjusted HR 0.48 [0.31-0.73]; P = 0.0005). Following propensity analysis, 2-year adjusted MACE rates were 7.4% versus 13.3% (HR 0.53 [0.35-0.79]; P = 0.004). Definite or probable stent thrombosis, adjudicated using identical criteria in both studies, occurred less frequently with CoCr-BP-BES (1.12% vs. 3.22%; adjusted HR 0.32 [0.11-0.9]; P = 0.034). In day-3 landmark analysis, the difference in 2-year MACE was no longer significant but there was a lower patient-orientated composite endpoint (11.7% vs. 18.4%; HR 0.6 [0.43-0.83]; P = 0.006) and a trend to lower target vessel failure (5.8% vs. 9.1%; HR 0.63 [0.4-1.00]; P = 0.078). Conclusion. At 2-year follow-up, propensity-adjusted analysis showed the thin strut (84-88um) Biomatrix Alpha CoCr-BP-BES was associated with improved clinical outcomes compared with the thicker strut (114-120um) Biomatrix Flex SSBP- BES.Published versio

Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

BACKGROUND: The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. METHODS: In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. RESULTS: We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. CONCLUSION: This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

Acute and long-term clinical and angiographic outcome after S-Stent implantation: S-Stent multicenter safety and efficacy trial

10.1002/ccd.20066Catheterization and Cardiovascular Interventions624439-444CARI

P2807Clinical outcomes with cobalt chromium biolimus eluting drug-eluting stents compared with stainless steel biolimus eluting drug-eluting stents in all-comers patients

AimsThinner stent struts may improve deliverability, conformability and reduce vessel injury. We report the first clinical outcomes of the thinner strut (84–88um) cobalt chromium biolimus eluting stent from the Biomatrix Alpha registry and compare these with objective performance criteria from the stainless steel BioMatrix Flex arm of the Leaders study.MethodsA total of 1257 patients were studied: 400 patients from 12 centres receiving ≥1 Biomatrix Alpha stent were prospectively enrolled into the Biomatrix Alpha registry and then underwent a pre-specified comparison with 857 patients who received a Biomatrix Flex stent in the Leaders study. The primary endpoint was major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) or clinically driven target vessel revascularization (TVR) at 9 months. Assuming a 9.2% event rate with BioMatrix Flex, a one-sided type I error (α) of 0.05, and a 4% non-inferiority margin, a sample size of 400 in the Biomatrix alpha registry had >80% power to conclude non-inferiority.ResultsBaseline characteristics in the Alpha registry were typical of an all-comers population with a mean age of 64.7±11.3, diabetes 19%, current smoking 21%, dyslipidemia 57%, hypertension 57%, total stent length per lesion 25.49±13.45, mean stents per procedure 1.59±0.88 and overlapping stents in 13.4%. Observed MACE at 9 months with Alpha was 3.94% (upper limit 5.98%) vs. 9.28% MACE rate with Flex stents in Leaders, which met pre-specified criteria for non-inferiority (p<0.001) and on post hoc testing for superiority yielded p<0.001 for Alpha vs Flex. Secondary endpoints with Alpha included clinically-driven TVR 2.6%, all-cause mortality rate 1.51% and definite/probable stent thrombosis 0.25%.While both Alpha and Leaders enrolled all-comers, Alpha included longer total stent length per lesion (25.49 vs 23.85mm, p<0.001) and more stents per procedure (mean 1.59 vs 1.34; p<0.001) but fewer patients with diabetes (19% vs 26%; p=0.0087), dyslipidemia (57 vs 65%; p=0.0037), prior MI (18.8% vs 32.2%; p<0.001) or acute coronary syndrome (41% vs 55%; p<0.001). To correct for these imbalances and to assess robustness further, a propensity score at the patient level data was undertaken (total sample size of 1257 patients; 400 from the Alpha registry and 857 from the LEADERS study). A propensity score stratification method was used obtaining 5 quintiles for adjusted analysis (each of the 5, containing 251 or 252 patients, 20%). In each of the strata as well as at the aggregate level, a p valve<0.005 was obtained confirming non-inferiority for the primary endpoint.ConclusionThe thinner strut (84–88um) cobalt chromium Biomatrix Alpha stent demonstrated low MACE rates at 9 months which were non-inferior to MACE outcomes with the stainless steel Biomatrix Flex in the Leaders study. The robustness of this finding was further confirmed by a propensity score analysis