Comments on “Association between immune checkpoint inhibitor‐induced myocarditis and concomitant use of thiazide diuretics”

I read with great interest the study by Mitsuboshi et al evaluating the association between thiazide use and immune checkpoint inhibitor (ICI) induced myocarditis.1 The authors reported that thiazide diuretics could be a risk factor for ICI-induced myocarditis. While the study findings were novel, several points should be clarified. First, it needs to be evident whether the patients treated with ICI-ICI combinations are excluded from the analyses in the method section. In several studies, the ICI-ICI combinations were associated with a higher risk of ICI-induced myocarditis.2 Additionally, the higher risk of ICI-induced myocarditis with ICI-ICI combinations was demonstrated from the Vigibase database.3 Therefore, the possibility of confounding due to combo ICI use should be noted. Furthermore, several studies reported a higher risk of ICI-induced myocarditis in patients with lung cancer than other tumors. While the authors stated that adding tumor type to the logistic regression method was not feasible due to limitations of the database, subgroup analyses according to tumor type are needed, especially for patients with lung cancer4 similar to the methodology of a previous study.5 Finally, thiazides are frequently used with ACE inhibitors or angiotensinogen receptor blockers and calcium channel blockers, among them the most frequently prescribed antihypertensive agents. Therefore, it should be clarified why only four antihypertensive agent classes were evaluated in the study and whether the data is certain regarding the use of thiazides as the monotherapy rather than the single-pill combination. An additional subgroup analysis should be conducted for the thiazide monotherapy and thiazide combinations. These subgroup analyses could further clarify the manuscript's findings, and if the association persists after subgroup analyses, it could lead to more precautious prescribing of thiazide diuretics in patients treated with ICIs. Thank you again for this wonderful work. The authors declare no conflict of interest.