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An earlier study by the same researchers of terazosin, an α-1 adrenergic receptor antagonist commonly used to manage benign prostatic hyperplasia, found that the drug and the closely related α-1 adrenergic receptor antagonists, the doxazosin and alfuzosin, bind together and improve cell energy levels.
In addition, these drugs have been shown to prevent or slow the progression of PD in animal models and in men with PD, according to the Truven Health Analytics MarketScan database in the United States, which took one of the drugs.
Seeking to deepen this potential link in men, the study authors evaluated 2 patient datasets, the Truven database from January 2001 to December 2017 and the national health registers in Denmark from January 1996 to December. 2017. Researchers compared men without PD who recently initiated terazosin / doxazosin / alfuzosin or tamsulosin, a drug with a similar indication used to treat an enlarged prostate but which does not increase cellular energy levels.
In Danish registers, male terazosin / doxazosin / alfuzosin pairs and tamsulosin users match the propensity score (N = 52,365; mean [SD] age, 67.9 [10.4] years) and the Truven database (N = 94883; mean [SD] age, 63.8 [11.1] years) were followed 1 year after the start of treatment. HRs were used to distinguish between the differences between the 2 treatment groups in the development of diagnosed PD or the use of drugs specific to PD.
When evaluating the two data cohorts, patients on terazosin / doxazosin / alfuzosin had a lower risk of developing PD, because patients in the Danish cohort had an HR of 0.88 (95% CI, 0 , 81-0.98) and patients in the Truven cohort had an HR of 0.63 (95% CI, 0.58-0.69).
“Despite the relative differences in the structure of the population and the health system, we found a similar protective effect in the two countries,” noted study author Jacob Simmering, PhD, assistant professor of internal medicine at the University of Iowa, in a statement.
In addition, a dose-response association was found with short-term, medium-term and long-term use of terazosin / doxazosin / alfuzosin: long-term users were associated with the lowest risk of developing PD. those observed in the two countries. cohort (short: HR, 0.95; 95% CI, 0.84-1.07; mean: HR, 0.88; 95% CI, 0.77-1.01; long: HR, 0, 79; 95% CI, 0.66-0.95) and the Truven cohort (short: HR, 0.70; 95% CI, 0.64-0.76; mean: HR, 0.58; CI 95%, 0.52-0.64; long: HR, 0.46; 95% CI, 0.36-0.57).
“The replication of the results in an international cohort is powerful evidence suggesting a causal effect,” Simmering concluded. “If these results are confirmed by further investigation, particularly a randomized clinical trial, terazosin may provide neuroprotection and potentially prevent – and not just manage – PD.
Reference
Simmering JE, Welsh MJ, Liu L, Narayanan NS, Pottegård A. Association of α-1 blockers improving glycolysis with the risk of developing Parkinson’s disease. JAMA Neurol. Published online February 1, 2020. doi: 10.1001 / jamaneurol.2020.5157
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