Key result
ACE inhibitors and ARBs show potential repurposing benefits for mood disorders and paralysis.
Why the study?
With large observational datasets available, this study sought to systematically screen for drug repurposing opportunities for antihypertensive drugs and elucidate relevant study design decisions and potential biases.
Does the initiation of specific antihypertensive classes prevent the onset of non-indicated diseases in adults over 50 with hypertension?
Observational (n=12,555)
Yes
Does the initiation of specific antihypertensive classes prevent the onset of non-indicated diseases in adults over 50 with hypertension?
Observational target trial emulation with hierarchical modeling can identify plausible drug repurposing opportunities across hundreds of endpoints, provided careful attention is paid to outcome definitions and residual confounding.
May suggest repurposing signals for antihypertensives; leaves open causal confirmation amid unmeasured confounding.
With availability of voluminous sets of observational data, an empirical paradigm to screen for drug repurposing opportunities (i.e., beneficial effects of drugs on nonindicated outcomes) is feasible. In this article, we use a linked claims and electronic health record database to comprehensively explore repurposing effects of antihypertensive drugs. We follow a target trial emulation framework for causal inference to emulate randomized controlled trials estimating confounding adjusted effects of antihypertensives on each of 262 outcomes of interest. We then fit hierarchical models to the results as a form of postprocessing to account for multiple comparisons and to sift through the results in a principled way. Our motivation is twofold. We seek both to surface genuinely intriguing drug repurposing opportunities and to elucidate through a real application some study design decisions and potential biases that arise in this context.
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Shahn et al. (2022) conducted an observational in Hypertension (n=12,555). Antihypertensive drugs (ACE inhibitors, ARBs, beta blockers, CCBs, thiazide diuretics) vs. Active comparison (other antihypertensive classes) was evaluated on 1-year cumulative incidence of 262 outcomes of interest (high-throughput screening). Target trial emulation identified potential repurposing effects for antihypertensives, such as ACE inhibitors for mood disorders and ARBs for paralysis, though susceptible to unmeasured confounding.
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