Anti-inflammatory strategies for atherosclerotic artery disease

ABSTRACT

Introduction

Atherosclerosis is the most frequent cause of coronary artery disease (CAD) and inflammation is a key driver of its pathogenesis. Targeting inflammation represents a novel therapeutic option beyond management of conventional cardiovascular risk factors. Recent efforts in cardiovascular research were aimed at investigating the efficacy and safety of existing and novel anti-inflammatory drugs.

Areas covered

The multimodal activation of the immune response enables several approaches to mitigate the inflammatory burden of atherosclerosis, which include general cardiovascular preventive measures from healthy lifestyle behaviors to medications with ancillary anti-inflammatory effects, such as lipid-lowering drugs. Clinical development of several specific anti-inflammatory drugs has been halted due to lack of proven efficacy in humans, while a number of trials are ongoing to test drugs targeting the NLRP3-IL1-IL6-hsCRP pathway, including drugs that are already in use for immune disorders (i.e. colchicine).

Expert opinion

The main challenge associated with specific anti-inflammatory drugs is the risk of immunological suppression. Due to positive results in recent randomized trials and a favorable safety profile, colchicine is expected to gain more popularity in the near future as an anti-inflammatory agent for cardiovascular prevention.

KEYWORDS:

• Atherosclerosis
• colchicine
• coronary artery disease
• NLRP3-IL1-IL6-hsCRP
• immune system
• inflammation

Article highlights

• Inflammation is a key driver of atherosclerosis, and a new field of cardiovascular research aims to develop drugs targeting inflammatory mediators.

• The multimodal activation of immune response enable many approaches to mitigate inflammatory burden, from general cardiovascular preventive measures to specific anti-inflammatory therapies.

• CANTOS trial showed that the use of canakinumab (human monoclonal antibody anti IL-1β) improves cardiovascular outcomes, and it is the first historically trial confirming the inflammatory hypothesis.

• Targeting inflammation requires caution due to safety concerns associated with modulation of the immune system.

• Due to positive results of colchicine in recent trials and its safety profile, the use of this drug in clinical practice seems favorable, as shown by its recent introduction in clinical guidelines on cardiovascular disease prevention for secondary prevention.

Declaration of interest

D Capodanno declares that he has received consulting and speaker’s fee from Amgen, Boehringer Ingelheim, Biotronik, Daiichi Sankyo, Sanofi Aventis outside the present work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.