Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER).

BACKGROUND: Low-density lipoproteins (LDLs) are removed by extracorporeal filtration during LDL apheresis. It is mainly used in familial hyperlipidemia. The PREMIER trial (Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen) evaluated LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. METHODS: We randomized 160 acute coronary syndrome patients at 4 Veterans Affairs centers within 72 hours of percutaneous coronary intervention to intensive lipid-lowering therapy (ILLT) comprising single LDL apheresis and statins versus standard medical therapy (SMT) with no LDL apheresis and statin therapy alone. Trial objectives constituted primary safety and primary efficacy end points and endothelial progenitor cell colony-forming unit mobilization in peripheral blood. RESULTS: Mean LDL reduction at discharge was 53% in ILLT and 17% in SMT groups (P<0.0001) from baseline levels of 116.3±34.3 and 110.7±32 mg/dL (P=0.2979), respectively. The incidence of the primary safety end point of major peri-percutaneous coronary intervention adverse events was similar in both groups (ILLT, 3; SMT, 0). The primary efficacy end point, percentage change in total plaque volume at 90 days by intravascular ultrasound, on average decreased by 4.81% in the ILLT group and increased by 2.31% in the SMT group (difference of means, -7.13 [95% CI, -14.59 to 0.34]; P=0.0611). The raw change in total plaque volume on average decreased more in the ILLT group than in the SMT group (-6.01 versus -0.95 mm3; difference of means, -5.06 [95% CI, -11.61 to 1.48]; P=0.1286). Similar results were obtained after adjusting for participating sites, age, preexisting coronary artery disease, diabetes mellitus, baseline LDL levels, and baseline plaque burden. There was robust endothelial progenitor cell colony-forming unit mobilization from baseline to 90 days in the ILLT group (P=0.0015) but not in SMT (P=0.0844). CONCLUSIONS: PREMIER is the first randomized clinical trial to demonstrate safety and a trend for early coronary plaque regression with LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01004406 and NCT02347098.

Clinical Outcomes and Cost Comparisons of Stent and Non-Stent Interventions in Infrainguinal Peripheral Artery Disease: Insights From the Excellence in Peripheral Artery Disease (XLPAD) Registry.

BACKGROUND: The contemporary limb outcomes and costs of stent-based vs non-stent based strategies in endovascular revascularization of femoropopliteal (FP) peripheral artery disease (PAD) are not well understood. METHODS AND RESULTS: We present data from the ongoing United States multicenter Excellence in Peripheral Artery Disease Registry between 2006-2016 to compare stent vs non-stent treatment outcomes and associated costs in FP interventions. A total of 2910 FP interventions were performed in 2162 patients (mean age, 66 years), comprising 1339 stent based (superficial femoral artery, 93%) in 1007 patients and 1571 non-stent interventions (superficial femoral artery, 85%) in 1155 patients. A growing trend for non-stent based interventions and a declining trend in repeat revascularization rate at 1 year were observed across years of registry enrollment. Stent implantation was the prevailing strategy in treating longer FP lesions (mean length, 152 mm vs 105 mm; P<.001) and chronic total occlusions (65% vs 40%; P<.001), while stent implantation was employed less frequently when treating in-stent restenotic lesions (14% vs 20%; P<.001). Stent and non-stent interventions had similar 1-year limb outcomes in all-cause death, target-limb revascularization, target-vessel revascularization, and major or minor amputation. The average procedure costs for the stent group were significantly higher than the non-stent group ($6215 vs $4790; P<.001). CONCLUSION: There is a growing trend for non-stent FP artery interventions, with a significant decline in 1-year target-limb revascularization rates over time. One-year limb outcomes in stent-based compared to non-stent interventions are similar; however, at a significantly higher procedural cost.

Comparison of Lower Extremity Endovascular Intervention Outcomes in Women Versus Men.

This study examined a gender difference in 12-month patient outcomes after endovascular intervention for symptomatic peripheral artery disease (PAD) utilizing propensity score-matched Excellence in Peripheral Artery Disease registry data. Mortality and repeat intervention outcomes after endovascular treatment in women compared with men in the existing literature are inconsistent and confounded by other risk factors. The study included 1,084 patients who underwent 1,702 endovascular procedures, at 8 non-Veterans Administration hospitals from January 2005 to October 2015. Frailty hazard ratios by gender for time-to-event analysis were estimated. Women made up about 40% of the study population. After propensity score matching, 449 women and 449 men were included in the analysis, in which women had similar baseline patient and lesion characteristics, laboratory data, procedural characteristics, and medical therapy as men. Within 12-month postintervention, women were at a lower risk of mortality than men (p = 0.05); however, they underwent significantly more frequent repeat revascularization procedures (p = 0.04). In subgroup analysis, women with superficial femoral artery disease were also at higher risk of 12-month repeat intervention than men (p <0.01) and had a higher mortality risk, albeit with an attenuated significance (p = 0.07). Women with PAD are at a higher risk of 12-month repeat intervention than men.

A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia.

Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH. The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes.