Bempedoic acid and increased serum uric acid levels: a matter of concern?

Several observational and genetic studies have found an association between high urate serum levels and hypertension, heart failure, and cardiovascular mortality. Bempedoic acid is a recently approved hypocholesterolemic agent acting by inhibiting the ATP citrate lyase and thus the hepatic cholesterol biosynthesis. Despite its optimal safety profile, a minor and reversible increase of serum uric acid levels has been observed. This effect is due to the inhibition by bempedoic acid of organic anion transporters 2 and 3 (OAT2 and OAT3) which mediate the renal excretion of urate.

The increased levels of uric acid were associated with higher incidence of gout and could potentially have a negative effect on cardiovascular diseases. However, any adverse urate effect seems not to be clinically dominant for at least two reasons: 1) the extent of cardiovascular events reduction with bempedoic acid was similar to the one achieved with statins for a given magnitude of LDL-C lowering; 2) bempedoic acid was not associated with increased incidence of hypertension and heart failure, cardiovascular diseases strictly associated with hyperuricemia. Finally, uric acid lowering agents have not consistently demonstrated cardiovascular benefit in randomized clinical trials, and other drugs increasing, to the same extent, uric acid plasma levels, i.e. thiazide diuretic, do not increase cardiovascular risk.

Thus, the iatrogenic increase of plasma uric acid levels by the inhibition of OAT does not appear to have a clinically relevant negative impact on cardiovascular diseases.