Common Heart Drug May Lead to False-Positive Amyloid Beta Plasma Test Results for Alzheimer Disease

People taking Entresto (sacubitril and valsartan; Novartis, East Hanover, NJ), a medication often prescribed for the treatment of cardiac failure, may show confounding results on plasma amyloid beta (Aβ)40/Aβ42 ratio tests for Alzheimer disease (AD), according to results of a study published in JAMA Neurology. Entresto is a combination neprilysin inhibitor and angiotensin II receptor blocker, and use of this medication can slow the physiological clearing of Aβ, resulting in increased Aβ40 and Aβ42 levels and a reduced Aβ42/Aβ40 ratio, posing the potential risk of false-positive Aβ test results and misclassification for AD positivity.

The study analyzed the effects of either Entresto or valsartan monotherapy on AD blood biomarkers in 92 patients with asymptomatic left ventricular systolic dysfunction after myocardial infarction from the RECOVER-LV clinical trial (NCT03552575). Plasma samples were collected at baseline, week 26, and week 52 and assessed for Aβ42, Aβ40 Aβ42/Aβ40, p-tau181, p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) biomarkers of AD.

In terms of results:

• Treatment with Entresto was associated with a significant 93% increase in Aβ40 levels from baseline to week 26, which persisted through week 52 (95% CI, 81.3% to 105.5%; P<.001)
• In those who received Entresto treatment, Aβ42 levels also increased significantly from baseline to week 26, persisting through 52 weeks (30.7%; 95% CI, 23.7% to 38.0%; P<.001).
• At week 26 and persisting at 52 weeks, Aβ42/Aβ40 ratios decreased significantly (31.7%; 95% CI, -34.1% to -29.1%; P<.001) in those receiving Entresto treatment.
• There were little to no changes in Aβ40 and Aβ42 levels seen in those who received valsartan monotherapy.
• There were no significant changes seen in ptau181, p-tau217, GFAP, and NfL levels for those taking Entresto or valsartan.