Inflammation and Atherothrombosis: New Clinical Aspects. The Year in ACS: Emerging Therapies in Atherothrombosis

The natural history of atherosclerotic plaques has been largely identified. On the contrary the occurrence of a clinical abrupt instability, such as an acute coronary syndrome due to thrombus formation upon a vulnerable coronary plaque, is still poorly understood and substantially unpredictable. The causes of such phenomenon are probably multiple: inflammation plays a key role in contributing to the highly thrombogenic milieu where both platelets and the coagulation cascade are activated. A better understanding of the mechanisms that underlie the evolution of the atherosclerotic disease is crucial to identify new therapeutic targets and to deliver innovative and more effective treatments. Focusing our attention on acute coronary syndromes (ACS), there are at least three different clinical conditions, which probably encompass the whole spectrum of the disease by a pathogenetic classification: ACS with obstructive atherosclerosis and systemic inflammation, ACS with obstructive atherosclerosis without inflammation and ACS without both anatomical and biological conditions.

In the first case, beyond optimizing the antithrombotic treatment in order to get more effectiveness without a significant increase of bleeding complications, the missing therapy is a specific anti-inflammatory treatment, which could modulate innate and/or adaptive immunity. In this regard several interventions, ranging from the administration of antagonists to key cytokines or impacting on alternative inflammatory pathways, to stimulation of regulatory T cells, are under clinical testing, and for some of them large phase III clinical trials are still ongoing or have shown conflicting results. In patients with occlusive atherosclerotic disease without inflammation plaque stabilization could be achieved with an early and intensive lipid lowering treatment: this is now possible with the highly effective statins plus ezetimibe and might be further potentiated in the future adding evolocumab or alirocumab in high-risk patients. Finally, epicardial and microvascular vasoconstriction is the key therapeutic target when ACS is not associated with obstructive atherosclerosis and new drug targeting vascular reactivity are highly expected.