Targeting residual inflammatory risk in coronary disease: to catch a monkey by its tail

Abstract

Patients with coronary disease remain at high risk for future cardiovascular events, even with optimal risk factor modification, lipid-lowering drugs and antithrombotic regimens. A myriad of inflammatory pathways contribute to progression of the atherosclerotic burden in these patients. Only in the last few years has the inflammatory biology of atherosclerosis translated into clinical therapeutic options. Low-dose colchicine can provide a clinically relevant reduction in the risk for composite and individual major cardiovascular outcomes in patients with acute and chronic coronary syndromes. Among others, its anti-inflammatory effects in atherosclerosis seem to be related to neutrophil recruitment and adhesion, inflammasome inhibition, and morphological changes in platelets and platelet aggregation. Future research is aimed at further elucidating its particular mechanism of action, as well as identifying patients with the highest expected benefit and evaluating efficacy in other vascular beds. These data will help to formulate the role of colchicine and other anti-inflammatory drugs in patients with coronary disease and atherosclerosis in general in the near future.

Keywords: Acute coronary syndrome; Atherosclerosis; Chronic coronary disease; Inflammation.

Fig. 1

Three different mechanisms that may contribute to the atheroprotective effects of colchicine in atherosclerosis are highlighted. IL interleukin, LDL low-density lipoprotein, NLRP3 nucleotide-binding oligomerisation domain-, leucine-rich repeat-, and pyrin domain-containing protein 3

Fig. 2

The expected absolute risk reduction and number needed to treat (NNT) when colchicine is added to optimal medical treatment. For risk prediction, an out-patient clinic example of a cigarette smoking 65-year old male with coronary disease was selected. He is treated with acetylsalicylic acid, has a systolic blood pressure below 140 mm Hg on antihypertensives and an LDL-cholesterol of 1.8 mmol/l using statins. The upper panel shows his probability (in per cent) of being free of myocardial infarction or stroke. The blue area under the curve represents his lifetime risk on the current therapy. The green area under the curve shows the change in expected lifetime risk after the introduction of anti-inflammatory treatment with colchicine. The middle panel shows his 10-year risk for myocardial infarction, stroke or cardiovascular death. The green bar shows the absolute reduction in his risk. The lower panel shows his lifetime risk for myocardial infarction, stroke or cardiovascular death. The green bar shows the absolute reduction in his risk. CVD cardiovascular disease, NNT number needed to treat