Inflammation in atherosclerosis: a Big Idea that has underperformed so far

For many years, inflammation has been a major concept in basic research on atherosclerosis and in the development of potential diagnostic tools and treatments. The purpose of this review is to assess the performance of this concept with an emphasis on recent clinical trials. In addition, contemporary literature may help identify new therapeutic targets, particularly in the context of the treatment of early, rather than end-stage, arterial disease.

Newly reported clinical trials cast doubt on the efficacy of colchicine, the sole anti-inflammatory agent currently approved for use in patients with atherosclerotic cardiovascular disease (ASCVD). New analyses also challenge the hypothesis that residual ASCVD event risk after optimal management of lipids, blood pressure, and smoking arises primarily from residual inflammatory risk. Current clinical practice to initiate interventions so late in the course of atherosclerotic arterial disease may be a better explanation. Lipid-lowering therapy in early atherosclerosis, possibly combined with novel add-on agents to specifically accelerate resolution of maladaptive inflammation, may be more fruitful than the conventional approach of testing immunosuppressive strategies in end-stage arterial disease. Also discussed is the ongoing revolution in noninvasive technologies to image the arterial wall. These technologies are changing screening, diagnosis, and treatment of atherosclerosis, including early and possibly reversable disease.

The burden of proof that the Big Idea of inflammation in atherosclerosis has clinical value remains the responsibility of its advocates. This responsibility requires convincing trial data but still seems largely unmet. Unfortunately, the focus on inflammation as the source of residual ASCVD event risk has distracted us from the need to screen and treat earlier.