Effect of Tafamidis on Dementia Medication Initiation: A Post-Hoc Analysis of the ATTR-ACT Trial

Transthyretin cardiac amyloidosis is a medical condition in which the protein transthyretin misfolds and aggregates together into microscopic clumps that deposit within the heart. The transthyretin protein is involved in transporting thyroid hormones throughout the body and is produced naturally in human physiology. When these normal proteins misfold and clump together, this condition is called cardiac amyloidosis. Cardiac amyloidosis can lead to abnormal heart function causing shortness of breath, swelling and abnormal electrical conduction in the heart that necessitates pacemaker implantation in some situations. Cardiac amyloidosis is frequently seen in patients with heart failure and cardiac valve disease, and with active screening can be identified in approximately 10-20% of patients in these populations. Dementia is a common condition seen alongside amyloidosis, affecting up to 50% of patients. Genetic mutations that predispose individuals to cardiac amyloidosis also predispose them to early onset dementia. It is unknown whether amyloidosis has a causal association with dementia or whether the two disorders are associated by common risk factors.

Tafamidis is a drug that stabilizes transthyretin proteins, prevents misfolding into clumps and significantly limits the progression of cardiac dysfunction. There may be benefit of tafamidis on the function of organs other than the heart, such as the central nervous system. The impact of transthyretin stabilization on the incidence and progression of dementia is unknown. This project aims to measure the impact of tafamidis treatment on the initiation of dementia and neuropsychiatric medications. Better understanding of the impact of tafamidis on patients' cognitive (brain) function will allow clinicians to have more informed discussions with their patients about the benefits of tafamidis treatment.

The ATTR-ACT trial was a clinical trial that randomized patients with cardiac amyloidosis to treatment with tafmidis and placebo. It showed a significant reduction in heart failure and death in patients treated with tafamidis. The cognitive impact of tafamidis has not yet been assessed. In this research project, we will explore the effect that tafamidis treatment had on the cognitive function of patients participating in the ATTR-ACT trial. We will compare how medications used to treat mental and cognitive disorders such as dementia, depression and psychosis were prescribed during the study and test for a difference in the use of these medications between patients receiving tafamidis and those receiving placebo.