Neurology Xagena

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Association of glycolysis-enhancing alpha-1 blockers with risk of developing Parkinson disease

Parkinson disease is a common neurodegenerative disease. A treatment that prevents or delays development of Parkinson is a critical unmet need.
Terazosin and closely related drugs were recently discovered to enhance glycolysis and reduce Parkinson progression in animal models and human clinical databases.

The objective of a new study was to determine whether use of Terazosin, Doxazosin, and Alfuzosin is associated with a decreased risk of developing Parkinson disease.

A cohort study used active comparator control and propensity score-matched data from Danish nationwide health registries, including the Danish National Prescription Registry, the Danish National Patient Registry, and the Danish Civil Registration System, from January 1996 to December 2017 and data from the Truven Health Analytics MarketScan database from January 2001 to December 2017.

Men without Parkinson disease who newly initiated Terazosin / Doxazosin / Alfuzosin therapy or Tamsulosin therapy, which is used for a similar indication ( benign prostatic hyperplasia or unspecified urinary problems ) but does not enhance glycolysis, and had at least 1 year of follow-up after medication start were included.
In Denmark, the database included all residents, while the Truven database is a compilation of insurance claims across the US.
Data were analyzed from February 2019 to July 2020.

Main outcomes and measures were differences in the hazard of developing Parkinson disease identified by diagnoses or use of Parkinson-specific medications between patients who ever used Terazosin / Doxazosin / Alfuzosin or Tamsulosin.

A cohort of 52 365 propensity score-matched pairs of Terazosin / Doxazosin / Alfuzosin and Tamsulosin users were identified in the Danish registries, of which all were male and the mean ( SD ) age was 67.9 ( 10.4 ) years, and 94 883 propensity score-matched pairs were identified in the Truven database, of which all were male and the mean ( SD ) age was 63.8 ( 11.1 ) years.

Patients in the Danish cohort who used Terazosin / Doxazosin / Alfuzosin had a hazard ratio ( HR ) for developing Parkinson of 0.88 ( 95% CI, 0.81-0.98 ), and patients in the Truven cohort had an hazard ratio of 0.63 ( 95% CI, 0.58-0.69 ).
There was a dose-response association with short-duration, medium-duration, and long-duration use of Terazosin / Doxazosin / Alfuzosin users having a decreasing hazard ratio in both the Danish cohort ( short: HR, 0.95; 95% CI, 0.84-1.07; medium: HR, 0.88; 95% CI, 0.77-1.01; long: HR, 0.79; 95% CI, 0.66-0.95 ) and Truven cohort ( short: HR, 0.70; 95% CI, 0.64-0.76; medium: HR, 0.58; 95% CI, 0.52-0.64; long: HR, 0.46; 95% CI, 0.36-0.57 ).

In conclusion, these data have suggested that users of Terazosin / Doxazosin / Alfuzosin are at lower hazard of developing Parkinson compared with users of Tamsulosin.
Future work is needed to further assess this association. ( Xagena )

Simmering JE et al, JAMA Neurol 2021; 78: 407-413