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Visiting researcher at the Broad Institute of MIT and Harvard
Using electronic health record (EHR) data from a large US healthcare system, we emulated a target trial comparing the effectiveness of two highly prescribed antihypertensive drug classes at preventing or delaying the onset of dementia: ACE inhibitors (ACEi) versus Angiotensin Receptor Blockers (ARBs).
To test the assumption that ACEi may have an off-target pathogenic mechanism affecting the risk of dementia, we compared patients initiating an ACEi versus an ARB in the US Research Patient Data Registry of Mass General Brigham, comprising two academic hospitals and 33 clinics located in the Greater Boston area.
We performed intention-to-treat analyses among 25,507 patients aged 50 and over, applying Inverse Propensity score of Treatment Weighting to balance the two treatment arms and accounting for the competing risk of death. We found that patients initiating an ACEi had a 1.1 percentage point higher risk of dementia five years after treatment initiation and that such a detrimental effect was more pronounced among men.
Ongoing work includes evaluating differential effects by brain penetrance, discovering subgroups of responders, and assessing the mediating role of blood pressure (BP) control with ACEi versus ARB.
Future research will incorporate longitudinal markers (e.g., BP, HbA1c, LDL) in time-to-event models and consider stroke incidence or recurrence under ACEi versus ARB initiation as a mediator.
Keywords: target trial emulation; electronic health records; drug repurposing; dementia; hypertension
