Selection of studies and inclusion and exclusion criteria

Eligible studies included participants aged 18 years or older, compared individuals receiving antihypertensive treatment (single agents) with those receiving placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or one blood pressure target compared with another. Although these study designs examine different types of intervention, all compared more antihypertensive treatment with less antihypertensive treatment, enabling the potential association with adverse events to be determined. Trials were also required to present data describing the association between antihypertensive treatment and at least one adverse event. Randomised controlled trials were included if they reported 50 or more adverse events in each specific category or had at least 650 patient years of follow-up.

To ensure study selection and data analysis remained manageable by avoiding small, early phase mechanistic studies, we specified a priori the limit on patient years of follow-up and number of outcome events. We chose the specific criteria to ensure each included study was large enough to accrue outcome events and provide reliable effect estimates. These criteria assumed an incidence of the primary outcome (falls) of 7.8 events per 100 patient years of follow-up, which would accrue at least 50 outcome events in each study.¹⁵

We excluded studies in specialist populations (children, pregnant women), and case reports, case series, or before and after studies. At least two members of the review team (AA, MS, BP, SF, CK, AD, JPS) independently reviewed study titles, abstracts, and full text articles. At each stage, the entire review team screened a proportion of articles to ensure consistency of decision making. Disagreements were resolved by a third reviewer (JPS).