Abstract and Introduction
Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.
Gout is a chronic inflammatory arthritis that affects 9.2 million adults in the US and is characterized by monosodium urate crystal deposition in the joints, secondary to elevated urate levels. Evidence suggests that hyperuricemia and gout are independently linked to an increased risk of coronary artery disease (CAD), heart failure (HF), and cardiovascular (CV) mortality. Patients with recent myocardial infarction (MI) and active gout have worse survival compared with patients with MI who are receiving treatment for gout. Interestingly, not all urate-lowering therapies (ULTs) improve CV outcomes. The URic acid Right for heArt Health Study Group (URRAH) confirmed the independent association of serum uric acid levels and fatal MI. Indeed, they demonstrated a prognostic uric acid cut-off of 5.26 as a predictor for fatal MI in women. Colchicine, which is a commonly used gout medication, has long been used in various pericardial diseases, including pericarditis, pericardial effusion, and effusive constrictive pericarditis. It has shown reductions in long-term CV adverse events in patients with recent MI and stable ischemic heart disease (SIHD). While the outcomes of the COLCOT (Colchicine Cardiovascular Outcomes Trial) trial generated interest, more research is required to fully incorporate colchicine into clinical practice.[5–7] Similarly, allopurinol and febuxostat have shown conflicting evidence with respect to CV outcomes.
Am J Cardiovasc Drugs. 2021;21(5):499-512. © 2021 Adis Springer International Publishing AG