A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Intracoronary Imaging, Cholesterol Efflux, and Transcriptomes After Intensive Statin Treatment: The YELLOW II Study.

BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of statins on clinical outcomes, the mechanisms underlying these effects remain elusive. OBJECTIVES: This study assessed changes in plaque morphology using intravascular imaging, with a comprehensive evaluation of cholesterol efflux capacity (CEC) and peripheral blood mononuclear cell (PBMC) transcriptomics in patients receiving high-dose statin therapy. METHODS: In a prospective study, 85 patients with stable coronary artery disease underwent percutaneous coronary intervention for a culprit lesion, followed by intracoronary multimodality imaging, including optical coherence tomography (OCT) of an obstructive nonculprit lesion. All subjects received 40 mg of rosuvastatin daily for 8 to 12 weeks, when the nonculprit lesion was reimaged and intervention performed. Blood samples were drawn at both times to assess CEC and transcriptomic profile in PBMC. RESULTS: Baseline OCT minimal fibrous cap thickness (FCT) was 100.9 ± 41.7 µm, which increased to 108.6 ± 39.6 µm at follow-up, and baseline CEC was 0.81 ± 0.14, which increased at follow-up to 0.84 ± 0.14 (p = 0.003). Thin-cap fibroatheroma prevalence decreased from 20.0% to 7.1% (p = 0.003). Changes in FCT were independently associated with CEC increase by multivariate analysis (ß: 0.30; p = 0.01). PBMC microarray analysis detected 117 genes that were differentially expressed at follow-up compared to baseline, including genes playing key roles in cholesterol synthesis (SQLE), regulation of fatty acids unsaturation (FADS1), cellular cholesterol uptake (LDLR), efflux (ABCA1 and ABCG1), and inflammation (DHCR24). Weighted coexpression network analysis revealed unique clusters of genes associated with favorable FCT and CEC changes. CONCLUSIONS: The study demonstrated an independent association between fibrous cap thickening and improved CEC that may contribute to morphological changes suggesting plaque stabilization among patients taking intensive statin therapy. Furthermore, the significant perturbations in PBMC transcriptome may help determine the beneficial effects of statin on plaque stabilization. (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering [YELLOW II]; NCT01837823).

Statins, atherosclerosis regression and HDL: Insights from within the plaque.

The idea that atheroma can regress is no longer a dream. We and others have discovered that decreasing the lipid content can directly lead to macrophage egress and plaque healing. The question, however, has remained as to how to translate these findings to the bedside. Taking advantage of imaging modalities such as intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS), we demonstrated in the YELLOW (Reduction in Yellow Plaque by Intensive Lipid Lowering Therapy) trial that short term treatment of high dose rosuvastatin treatment can lead to a decrease in lipid content in plaques. It is important to note that optical coherence tomography (OCT), a high resolution imaging modality, was not performed during the first study and therefore, only a very limited assessment of the effect of statin therapy on measures of plaque stabilization could be made. The YELLOW II trial is the first to our knowledge to determine whether these data can be extrapolated and how it relates to HDL function, alterations in macrophage gene expression, and plaque morphology. While tremendous progress has been made, our research serves as a reminder that angiography is simply luminography and it is features such as thin cap fibroatheroma and lipid burden, for example, that likely modulate the syndromes seen in clinical practice. Ongoing studies such as ours may provide novel pathways for diagnosis and therapy, with the ultimate goal of reducing the burden of cardiovascular disease.

Refractory angina pectoris: mechanism and therapeutic options.

As the survival of patients with primary coronary events continues to increase, the number of patients presenting with coronary artery disease unsuitable to further revascularization techniques and symptoms refractory to medical therapy also continues to rise. The aims of this review were to define the population of patients with refractory angina pectoris and to present the therapeutic options currently available for this condition. Refractory angina pectoris is defined, and traditional medical therapies are discussed. Then, current therapeutic options for patients with refractory angina are extensively reviewed. A multitude of therapeutic options exist for patients with refractory angina pectoris. Small, uncontrolled studies have shown a potential benefit for additional antiplatelet and antithrombotic therapy. In randomized trials, neurostimulation has been shown to be effective in reducing angina symptoms. Enhanced external counterpulsation is a viable treatment option for select patients with refractory angina. In many randomized trials, laser revascularization has been shown to diminish angina symptoms, although no placebo-controlled studies exist to date. Gene therapy is a promising area of research in this field. Percutaneous in situ coronary venous arterialization is in its infancy, but may be able to treat many patients if proved successful. No data support the role of chelation therapy in this population. Heart transplantation remains a final option for these patients. Further research of the techniques mentioned in this review is warranted. The importance of randomized, double-blinded, placebo-controlled trials cannot be overemphasized, as the placebo effect of these therapies is probably marked.