Alberto Lorenzatti, MD, FACC*
Even after optimal pharmacotherapy and precise revascularizations, the recurrence of myocardial infarction remains at approximately one-third for the 5 year-period after an acute coronary syndrome.1,2 The recognition, in the past few decades, of the key involvement of inflammation in the pathogenesis of atherosclerosis, has changed the concept of this process away from being considered an exclusively lipid-driven disease, and has opened new opportunities for addressing this unacceptably high CVD residual risk.3
Recently, the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS trial) provided convincing evidence that targeting the IL-1β inflammatory pathway by the selective antibody canakinumab reduces major cardiovascular events, and significantly lowers IL-1β, IL-6 and hsCRP, without affecting cholesterol levels, with the benefit provided being directly associated with the magnitude of IL-6 and hsCRP lowering.4,5 Nevertheless, clinical application related to this new evidence and associated knowledge has not yet been implemented in clinical practice.
The latest Cardiovascular Inflammation Reduction Trial (CIRT study), low-dose methotrexate, by contrast, did not reduce cardiovascular events, probably because there was no reduction in either inflammatory mediators or biomarkers.6
Despite these two contemporary studies, more research is still required on the role of anti-inflammatory and immuno-modulating interventions in CVD.
The classic anti-inflammatory drug colchicine – used for treating gout – represents a potentially useful agent for targeting inflammation in atherosclerosis, and is currently being tested for CV protection in at least two double-blind, placebo-controlled trials: Low Dose Colchicine for secondary prevention in stable Coronary Heart Disease (LoDoCo2) and Colchicine Cardiovascular Outcomes Trial (COLCOT) in patients after ACS.7
To date, canakinumab is the only anti-inflammatory intervention that has been proven to reduce CV events in patients with established CAD and elevated hsCRP. However, whether it can be included among the secondary prevention armamentarium will depend on several factors including additional evidence, side effects and cost. In addition, a wide spectrum of possibilities is now available for exploring new anti-cytokine therapies for addressing inflammation in atherosclerosis.8
Alberto Lorenzatti, MD, FACC1,2
- DAMIC Medical Institute / Rusculleda Foundation for Research, Cordoba, Argentina.
- Department of Cardiology, Cordoba Hospital, Cordoba, Argentina.
- Wong ND, Zhao Y, Quek RGW, Blumenthal RS, Budoff MJ, Cushman M, et al. Residual atherosclerotic cardiovascular disease risk in statin-treated adults: The Multi-Ethnic Study of Atherosclerosis. Journal of clinical lipidology. 2017;11(5):1223-33.
- Fox KA, Carruthers KF, Dunbar DR, Graham C, Manning JR, De Raedt H, et al. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J. 2010;31(22):2755-64.
- Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868-74.
- Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-31.
- Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391(10118):319-28.
- Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2018.
- Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61(4):404-10.
- Ridker PM. Anticytokine Agents. Circ Res. 2019;124(3):437-50.