Abstract：
OBJECTIVE: Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB).
METHODS: We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression.
RESULTS: Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses.
CONCLUSIONS: We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.
METHODS: This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.
METHODS: We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression.
RESULTS: Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses.
CONCLUSIONS: We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.
METHODS: This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.
摘要：
目标：特拉唑嗪，多沙唑嗪,和阿夫唑嗪(Tz/Dz/Az)是α-1肾上腺素能受体拮抗剂,其也结合并激活糖酵解中的关键三磷酸腺苷(ATP)产生酶。据推测，大脑中能量可用性的增加可能会减缓或预防神经变性，可能通过减少α-突触核蛋白的积累。最近的工作表明，在动物和人类研究中，在帕金森氏症中使用Tz/Dz/Az具有潜在的神经保护作用。我们研究了Tz/Dz/Az在密切相关的疾病中的神经保护作用。路易体痴呆（DLB）。
方法：我们在MerativeMarketscan数据库中使用了新的用户主动比较器设计，以识别新开始服用Tz/Dz/Az或2种比较药物的无DLB病史的男性。我们的比较药物是其他通常用于治疗良性前列腺增生但不增加ATP的药物：α-1肾上腺素能受体拮抗剂坦索罗辛或5α-还原酶抑制剂（5ARI）。我们在倾向评分和随访时间上对队列进行了匹配。我们对匹配的队列进行了随访，以使用Cox比例风险回归评估发展为DLB的风险。
结果：新开始使用Tz/Dz/Az的男性患DLB的风险低于服用坦索罗辛的匹配男性（n=242,716,728,256人年，危险比[HR]0.60，95%CI0.50-0.71)或5ARI(n=130,872，399,316人年，HR0.73，95%CI0.57-0.93）。而服用坦索罗辛的男性的危害与服用5ARI的男性相似（n=159,596,482,280人年，HR1.17，95%CI0.96-1.42）。这些结果对一些敏感性分析是稳健的。
结论：我们发现服用Tz/Dz/Az的男性与服用其他药物的类似男性相比，DLB的危害更低。当结合Tz/Dz/Az关于帕金森病的文献，我们的研究结果表明,糖酵解增强药物在神经退行性突触核蛋白病中可能具有广泛的保护作用.未来需要一项随机试验来评估这些因果关系。
方法：本研究提供了III类证据，证明使用Tz/Dz/Az可降低成年男性患DLB的比率。
方法：我们在MerativeMarketscan数据库中使用了新的用户主动比较器设计，以识别新开始服用Tz/Dz/Az或2种比较药物的无DLB病史的男性。我们的比较药物是其他通常用于治疗良性前列腺增生但不增加ATP的药物：α-1肾上腺素能受体拮抗剂坦索罗辛或5α-还原酶抑制剂（5ARI）。我们在倾向评分和随访时间上对队列进行了匹配。我们对匹配的队列进行了随访，以使用Cox比例风险回归评估发展为DLB的风险。
结果：新开始使用Tz/Dz/Az的男性患DLB的风险低于服用坦索罗辛的匹配男性（n=242,716,728,256人年，危险比[HR]0.60，95%CI0.50-0.71)或5ARI(n=130,872，399,316人年，HR0.73，95%CI0.57-0.93）。而服用坦索罗辛的男性的危害与服用5ARI的男性相似（n=159,596,482,280人年，HR1.17，95%CI0.96-1.42）。这些结果对一些敏感性分析是稳健的。
结论：我们发现服用Tz/Dz/Az的男性与服用其他药物的类似男性相比，DLB的危害更低。当结合Tz/Dz/Az关于帕金森病的文献，我们的研究结果表明,糖酵解增强药物在神经退行性突触核蛋白病中可能具有广泛的保护作用.未来需要一项随机试验来评估这些因果关系。
方法：本研究提供了III类证据，证明使用Tz/Dz/Az可降低成年男性患DLB的比率。
