Study power
We calculated that, for a two groups survival analysis comparison on a total time of 3 years and 400 patients per group, we able to detect as significant an HR of 0.8 or lower with a type 1 error alpha = 0.05 and a power of 80%.

Statistical analysis

Median and interquartile range (Q1 – Q3) was used to describe age distribution due to its non-normality. As well, the non-parametric Wilcoxon test was used to assess the difference of age between the two groups of patients exposed or non-exposed to montelukast. Pearson’s Chi-square test for association was used to test the association of montelukast exposure with the qualitative variables. All the available variables were, potentially, considered as predictors of a CV event. However, because some drugs were used by less than 10 patients, those were not considered in the subsequent analysis. Cox (proportional hazards) regression analysis was performed pooling IS and MI as target events. All the CV events occurred among patients taking anti-hypertensive, anti-platelet, or anti-cholesterol drugs, i.e. among patients at increased ‘CV risk’. For this reason, those variables could not be included in a classical Cox regression models, but rather we used both a propensity score (PS) matching using different calipers (0.4-01) and a Cox model adjusted for PS. Since our study is a retrospective one, PS method was used for reducing the effects of confounders. PS has been calculated using a logistic regression on the treatment variable (i.e. exposure to montelukast), considering age, gender, residence, education, income, as well as anti-hypertensive, anti-platelet, diuretic, hypoglycemic, anti-hypercholesterolemic and anti-androgen drugs as potential predictors of taking treatment. Concerning qualitative ordinal variables with more than two levels, analyses were performed both using all levels and aggregating levels in order to obtain binary variables. IS or MI were considered as events for survival analysis. For every patient the observation started January 1st, 2012. All the patients have been observed up to three years (no drop out) or until the first event. Event-free Kaplan-Meier survival curves were drawn for major CV events, and the difference between two curves was tested using the log-rank statistics. For all the analyses, p-values lower than 0.05 were considered statistically significant. All statistical analyses were performed using SAS 9.4 (SAS Institute, Cary, NC, USA)