Lithium toxicity from angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker co-prescription: A...

Initiating an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) in patients taking lithium may increase the concentration of serum lithium and the risk of lithium toxicity.

In patients taking lithium, to compare the 90-day risk of lithium toxicity following a new co-prescription of an ACEi or ARB versus a new co-prescription of a beta-blocker.

Population-based cohort study in Ontario, Canada, from 2002 to 2024. Patients 50 years of age and older taking lithium who were co-prescribed an oral ACEi or ARB (n = 2267) or a beta-blocker (n = 2110). Outcomes were assessed within 90 days of initiating the drug co-prescription. The primary outcome was a hospital admission with lithium toxicity. Secondary outcomes were all-cause mortality and all-cause hospitalization. Overlap weighting using propensity scores was used to balance groups on indicators of baseline health. Risk ratios (RR) were obtained using weighted log-binomial regression, and risk differences (RD) were obtained using weighted binomial regression.

In lithium users, co-prescription of an ACEi or ARB versus a beta-blocker was not associated with a higher risk of hospital admission with lithium toxicity (47/2267 patients co-prescribed an ACEi or ARB (2.1%) versus 54/2110 patients co-prescribed a beta-blocker (2.6%); weighted RR 0.72 (95% CI, 0.47 to 1.11); weighted RD -0.75% (95% CI, -1.74% to 0.25%). In lithium users, co-prescription of an ACEi or ARB versus a beta-blocker was not associated with a higher risk of all-cause mortality or all-cause hospitalization.

The findings of this study suggest that the higher risk of lithium toxicity in patients co-prescribed an ACEi or ARB observed in some prior studies may be overstated.