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Initial randomized trials of cholesteryl ester transfer protein (CETP) inhibitors were terminated early owing to adverse effects or futility. The REVEAL trial now shows the benefit of CETP inhibition in coronary heart disease. Despite raising HDL-cholesterol levels, the cardiovascular effect of CETP inhibitors is probably due to lowering of non-HDL-cholesterol levels.
Contradictory results in animal atherosclerosis studies might partly explain limited translational efficacy, and also undermine the confidence of funding agencies, politicians, and the public in scientists and their research. A new guideline paper provides recommendations aimed at standardization of animal atherosclerosis studies to improve the reproducibility of this research.
A novel image-analysis method using standard CT imaging demonstrates that changes in the CT signal of coronary perivascular adipose tissue are associated with the degree of inflammation in adjacent coronary plaques. This exciting development might become a useful adjuvant clinical tool, although further validation and prospective outcome studies are required.
The benefits of aspirin in protecting against thrombotic occlusions are well-established. However, aspirin use has also been linked to increased gastrointestinal and fatal bleeding in elderly patients. Safer preventive approaches should be considered in the elderly population, including reductions in aspirin dose, alternative daily regimens, and individualized treatment strategies.
Revascularization of ischaemia-injured myocardium is critical for functional recovery. A new study shows that endothelial cells of neovessels in the injured heart derive from pre-existing endothelial cells. This new finding focuses research on therapeutic strategies to direct the neovasculature to deliver oxygen and nutrients effectively to the ischaemic myocardium.
The nocebo effect might be involved in a substantial proportion of patients experiencing muscle symptoms attributed to statin therapy. This observation underlines the importance of patient counselling and physician opposition to misinformation. Nonetheless, clinicians face a reality in which many patients do not tolerate adequate statin therapy despite rigorous efforts. Novel treatment strategies are, therefore, much needed.
The investigators of PRECISE-DAPT devised a five-item score to predict out-of-hospital bleeding risk in patients treated with dual antiplatelet therapy (DAPT) after coronary stenting. In patients at high risk of bleeding treated with prolonged DAPT, significantly more bleeding events were observed, with no reduction in ischaemic events.
Accumulation of foam cells — macrophages with intracellular lipid droplets — in arterial walls is a hallmark of atherosclerosis. Bernelot Moens and colleagues report increases in circulating monocytes with intracellular lipid accumulation, associated CCR2 expression, and enhanced monocyte migration in patients with familial hypercholesterolaemia. These changes could be reversed by PCSK9-inhibitor treatment.
PCSK9 inhibitors are the most potent LDL-cholesterol lowering drugs on the market. The latest cardiovascular outcome trials of these anti-PCSK9 monoclonal antibodies show positive results with fully-human antibodies, although with modest effect on major adverse cardiovascular events in patients who attain LDL-cholesterol target levels with statin therapy, whereas humanized antibodies are associated with the development of neutralizing antibodies.
The ESC has updated its 2006 consensus statement on clinical investigation of autologous adult stem cells for the treatment of acute myocardial infarction and heart failure. This initiative by a group of leaders in the field stimulates much-needed reflection and provides guidance to make cell therapy a clinical reality. Here, we offer our own perspective.
The optimal blood-pressure (BP) goals for elderly patients remain inconclusive, despite the recent publication of meta-analyses comparing intensive BP control with standard BP control. In searching for therapeutic approaches in these patients, researchers should change the focus from optimal BP values to a more holistic, individual approach.
Inflammation is a recognized component of many diseases, including atherosclerosis and its complications. IL-1β is a crucial cytokine promoting the inflammatory cascade. In the February 2017 issue of Nature Medicine, Furman et al. show that metabolites can trigger inflammation via inflammasome-dependent IL-1β production in elderly individuals. Intriguingly, caffeine is protective by offsetting this activation.
The ACCORDION trial, an extension of the ACCORD trial, confirms earlier findings showing that addition of fenofibrate to background statin therapy does not reduce cardiovascular events. However, cardiovascular events are reduced in patients with dyslipidaemia. Future trials with fibrates should restrict inclusion to patients with dyslipidaemia that persists despite statin therapy.
In the PRECISION trial involving patients with arthritis, moderate doses of a selective cyclooxygenase 2 inhibitor were not associated with increased cardiovascular events compared with submaximal doses of nonselective NSAIDs. The balance between pain relief and cardiovascular risk with NSAIDs should be further investigated in patients with chronic inflammatory rheumatic diseases.
Atherosclerosis is a disease of ageing, and the most common cause of death in the industrialized world. Cell senescence and the therapeutic removal of senescent cells using 'senolytics' are topical areas of science and translational medicine. A new study reports surprising findings on cell senescence and atherosclerosis with important therapeutic implications.
Ischaemic cardiomyopathy leads to destruction of cardiomyocytes beyond the regenerative potential of the adult human heart. The murine heart can regenerate in utero and shortly after birth, but oxidative stress eventually arrests cardiomyocyte division. Chronic hypoxia in mice has now been shown to induce the cell cycle in cardiomyocytes, resulting in cardiac regeneration.
When administered in the setting of an acute myocardial infarction, β-blockers decrease myocardial ischaemia, reduce the rates of reinfarction and serious ventricular tachyarrhythmias, and have substantial early benefits. However, the benefits of prolonged β-blockade after acute myocardial infarction are unproven and are discussed.
Blood-pressure lowering has undisputable benefits, but the optimal values to which blood pressure should be lowered are debated. Interpretation of recent trials is controversial, and post-hoc analyses to investigate the inflection point of the curve relating events to blood pressure are disputed. Meta-analyses of randomized trials and prospective, cohort studies might guide decision-making.
The ANTARCTIC trial does not provide sufficient evidence to refute the utility of platelet function monitoring in patients with high risk of coronary artery disease. Future trials on personalized antiplatelet therapy should try to address the limitations of previous studies.
The primary analysis of FIRE AND ICE demonstrated that cryoablation was noninferior to radiofrequency ablation for the primary efficacy end point of first documented clinical failure. Secondary analysis suggested that cryoablation had advantages over radiofrequency ablation in terms of rehospitalizations and repeat procedures; however, the validity of these results must be questioned.