Abstract Background Despite the extensive evidence for the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects in remain elusive. Objectives To assess the ...changes in plaque morphology by intravascular imaging with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cells (PBMC) transcriptomics in patients receiving high-dose statin therapy. Methods In a prospective study, 85 patients with stable multivessel coronary artery disease underwent percutaneous coronary intervention for a culprit lesion followed by intracoronary multi-modality imaging including optical coherence tomography (OCT) of an obstructive non-culprit lesion (NCL). All subjects received 40 mg of rosuvastatin every day for 8-12 weeks, when the NCL was reimaged and intervention was performed. Blood samples were drawn at both times to assess cholesterol CEC and transcriptomic profile in PBMC. Results Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 μm and CEC 0.81 ± 0.14, which increased upon follow-up-FCT (108.6 ± 39.6 μm, P<0.001), CEC (0.84 ± 0.14, P=0.003). The prevalence of thin-cap fibroatheroma reduced from 20.0% to 7.1% (P=0.003). The changes in FCT were independently associated with the increase in CEC by multivariate analysis (β, 0.30; 95%CI, 0.07-0.54; P=0.01). Microarray analysis of PBMC detected 117 differentially expressed genes at follow-up compared to baseline including genes playing key role in cholesterol synthesis ( SQLE ), regulation of fatty acids unsaturation ( FADS1 ), cellular cholesterol uptake ( LDLR ), efflux ( ABCA1 , ABCG1 ) and inflammation ( DHCR24 ). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable changes in FCT and CEC. Conclusions The study demonstrates an independent association between the thickening of the fibrous cap and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients on intensive statin therapy. Furthermore, the significant transcriptomic perturbations related to cholesterol synthesis, regulation of fatty acid unsaturation, cellular cholesterol uptake, efflux and inflammation may co-operate in determining the beneficial effects of statin on plaque stabilization.
Abstract Background Many low-risk acute coronary syndrome (ACS) patients are not pre-treated with a P2Y12 receptor inhibitor, and percutaneous coronary interventions (PCIs) are often performed on an ...ad hoc basis in this population. Pharmacodynamic (PD) studies comparing ticagrelor versus clopidogrel in patients undergoing ad hoc PCI are lacking. Objectives This study sought to assess PD effects of ticagrelor versus clopidogrel loading dose (LD) in the peri-procedural period among troponin-negative ACS patients undergoing ad hoc PCI. Methods This was a prospective, open-label, randomized, multicenter, parallel-group, phase IV PD study. One hundred P2Y12 inhibitor-naïve patients presenting with biomarker-negative ACS and undergoing ad hoc PCI, on a background of aspirin therapy, were randomized to receive either ticagrelor 180 mg LD or clopidogrel 600 mg LD. Platelet reactivity (P2Y12 reaction units PRU; VerifyNow assay) was measured at 5 time points: pre-LD, at 0.5, 2, and 8 h post-LD, and at end of PCI. The primary endpoint was PRU levels 2 h post-LD; secondary endpoints included PRU levels at all other time points and inhibition of platelet aggregation; an exploratory analysis evaluated rates of high on-treatment platelet reactivity (HPR) (PRU >208). Results At 2 h, PRU levels were significantly lower with ticagrelor versus clopidogrel (98.4 ± 95.4 vs. 257.5 ± 74.5; p < 0.001; primary endpoint). PRU levels diverged as early as 0.5 h post-LD, with significant differences observed by the end of PCI (mean 0.6 h post-LD) and maintained up to 8 h post-LD. HPR rates were also significantly reduced with ticagrelor compared with clopidogrel at the end of PCI (p = 0.030), and at 2 h (p < 0.001) and 8 h (p < 0.001) after LD. Conclusions In low-risk ACS patients undergoing ad hoc PCI, ticagrelor LD provides more prompt and potent platelet inhibition, and lower HPR rates, compared with clopidogrel LD. (Ad Hoc Percutaneous Coronary Intervention Study in Acute Coronary Syndrome Patients: NCT01603082 )
Objectives We evaluated the impact of the everolimus-eluting stent (EES) on the frequency of stent thrombosis (ST), target vessel revascularization (TVR), myocardial infarction (MI), and cardiac ...death in randomized controlled trials comparing the EES to non–everolimus-eluting drug-eluting stents (EE-DES). Background Whether or not the unique properties of the EES translate into reductions in ST remains unknown. Methods We searched MEDLINE, Scopus, the Cochrane Library, and Internet sources for articles comparing outcomes between EES and non–EE-DES without language or date restriction. Randomized controlled trials reporting the frequency of ST were included. Variables relating to patient and study characteristics and clinical endpoints were extracted. Results We identified 13 randomized trials (n = 17,101) with a weighted mean follow-up of 21.7 months. Compared with non–EE-DES, the EES significantly reduced ST (relative risk RR: 0.55; 95% confidence interval CI: 0.38 to 0.78; p = 0.001), TVR (RR: 0.77; 95% CI: 0.64 to 0.92; p = 0.004), and MI (RR: 0.78; 95% CI: 0.64 to 0.96; p = 0.02). There was no difference in cardiac mortality between the groups (RR: 0.92; 95% CI: 0.74 to 1.16; p = 0.38). The treatment effect was consistent by different follow-up times and duration of clopidogrel use. The treatment effects increased with higher baseline risks of the respective control groups with the strongest correlation observed for ST (R2 = 0.89, p < 0.001). Conclusions Intracoronary implantation of the EES is associated with highly significant reductions in ST with concordant reductions in TVR and MI compared to non–EE-DES. Whether these effects apply to different patient subgroups and DES types merits further investigation.
Objectives This study sought to determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content. Background Statin therapy significantly reduces the risk for ...thrombotic events. Whether or not these benefits are attributable to reduction in plaque lipid content remains to be properly documented in human obstructive coronary artery disease (CAD). Methods We randomized 87 patients with multivessel CAD undergoing percutaneous coronary intervention and at least 1 other severely obstructive (fractional flow reserve FFR ≤0.8) nontarget lesion (NTL) to intensive (rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. NTLs were evaluated at baseline and after 7 weeks of therapy with FFR, near-infrared spectroscopy, and intravascular ultrasound. The primary endpoint was the change in lipid-core burden index at the 4-mm maximal segment (LCBI4mm max), wherever this occurred within the lesion. Results Upon follow-up, median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (−149.1 −210.9 to −42.9 vs. 2.4 −36.1 to 44.7; p = 0.01). Results remained consistent after adjustment for baseline differences in LCBI between groups and use of change in LCBI across the entire lesion as the dependent outcome. Conclusions Short-term intensive statin therapy may reduce lipid content in obstructive lesions. These hypothesis-generating findings warrant confirmation in larger studies with longer follow-up. (Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy YELLOW); NCT01567826 )
Coronary bifurcations are prone to develop atherosclerotic plaque because of turbulent blood flow and high shear stress. When compared with nonbifurcation coronary interventions, bifurcation ...interventions have historically reported a lower rate of procedural success, higher procedural costs, longer hospitalization, and higher clinical and angiographic restenosis. Treating bifurcation lesions is challenging, but a simple algorithm based on the side branch size, stenosis, and angulation can be used. The ongoing development of novel drug-eluting stent devices designed specifically for coronary bifurcations and the large randomized clinical trials being conducted to address their utility will add to the already present literature regarding treatment of coronary bifurcation lesions.
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