Lithium toxicity from angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker co-prescription: a population-based cohort study

Rationale — 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.

Objective — 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.

Methods — 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.

Results — 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.

Conclusion — 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.