Comparison of antihypertensive drug classes for dementia prevention

Background: There is evidence that hypertension in midlife can increase the risk of Alzheimer’s disease and vascular dementia in late life. In addition, some antihypertensive drugs have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose antihypertensive drugs for the prevention of dementia. This study systematically compared seven antihypertensive drug classes for this purpose, using the Clinical Practice Research Datalink.

Methods: Treatments for hypertension were assessed in an instrumental variable (IV) analysis to address potential confounding and reverse causation. Physicians’ prescribing preference was used as an ordinal instrument, defined by the physicians’ last seven prescriptions. Participants were new antihypertensive users between 1996-2016, aged 40 and over.

Results: We analysed 849,378 patients with total follow up of 5,497,266 patient-years. Beta-adrenoceptor blockers and vasodilator antihypertensives were found to confer small protective effects – for example, beta-adrenoceptor blockers resulted in 13 (95% CI: 6 to 20) fewer cases of any dementia per 1000 treated compared with other antihypertensives.

Conclusions: We found small differences in antihypertensive drug class effects on risk of dementia outcomes. However, we show the magnitude of the differences between drug classes is smaller than previously reported. Future research should look to implement other causal analysis methods to address biases in conventional observational research with the ultimate aim of triangulating the evidence concerning this hypothesis.