Percutaneous coronary intervention strategy for acute coronary syndrome caused by spontaneous coronary artery dissection for relieving ongoing ischemia—Case series and literature review

AbstractAlthough spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS) or sudden cardiac death, its standard management, especially primary percutaneous coronary intervention (PCI) in ACS patients with ongoing ischemia, has not been established. We experienced three ACS patients with SCAD who were treated with a different strategy of primary PCI. Each PCI strategy led to different clinical and procedural results. We describe here such PCI strategies and results, and also discuss the literature regarding primary PCI strategies for SCAD-induced ACS patients with ongoing ischemia.<Learning objective: SCAD is a cause of ACS. However, the treatment strategy of primary PCI for SCAD has not been fully investigated. We used different PCI strategies for three SCAD patients with ongoing ischemia. Our case series suggested that plain old balloon angioplasty is an acceptable option to avoid coronary stenting because the majority of patients were young menstruating women. Coronary vasospasm might be associated with SCAD. Treatment with vasodilators could be a potential pharmacological option for avoiding recurrence of SCAD.

Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial

AbstractBackgroundAlthough the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy.PurposeThe Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD.MethodsThe study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis.ConclusionPRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population

Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention The Multicenter Randomized Controlled PRECISE-IVUS Trial

AbstractBackgroundDespite standard statin therapy, a majority of patients retain a high “residual risk” of cardiovascular events.ObjectivesThe aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI).MethodsThis trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients.ResultsThe combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (–1.538%; 95% confidence interval [CI]: –3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (–1.4%; 95% CI: –3.4% to –0.1% vs. –0.3%; 95% CI: –1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.ConclusionsCompared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition–induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380

Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance

Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition-sensitive and -resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+ tumor-associated macrophages (TAMs) as a key factor correlated with immune resistance. In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. Targeted delivery of a long peptide antigen to TAMs by using a nano-sized hydrogel (nanogel) in the presence of a TLR agonist activated TAMs, induced their antigen-presenting activity, and thereby transformed the resistant tumors into tumors sensitive to adaptive immune responses such as adoptive transfer of tumor-specific T cell receptor-engineered T cells. These results indicate that the status and function of TAMs have a significant impact on tumor immune sensitivity and that manipulation of TAM functions would be an effective approach for improving the efficacy of immunotherapies