Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
PLoS Med. 2021 Jul 19;18(7):e1003707. doi: 10.1371/journal.pmed.1003707. eCollection 2021 Jul.
Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)-modulating effects, has additional benefits compared to other ARBs remains unclear.
Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data.
The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.
血管紧张素受体阻滞剂（ARBs）可能对高血压（HTN）患者的痴呆发生有保护作用。然而，替米沙坦作为一种具有过氧化物酶体增殖物激活受体γ（PPAR-γ）调节作用的 ARB，与其他 ARB 相比是否具有额外的益处尚不清楚。
在 1997 年至 2013 年间，从台湾的全民健康保险研究数据库中确定了 2166944 例 2 型糖尿病（T2DM）患者。将使用 ARBs 的 HTN 患者纳入研究。排除有中风、创伤性脑损伤或痴呆病史的患者。最后，纳入了 65511 名符合条件的患者，分为替米沙坦组和非替米沙坦 ARB 组。采用倾向评分匹配（1:4）来平衡基线特征和药物的分布。主要结局是痴呆的诊断。次要结局包括阿尔茨海默病的诊断、症状性缺血性卒中（IS）的发生、任何 IS 和全因死亡率。使用 Cox 比例风险模型比较组间风险。统计学意义设为 p<0.05。替米沙坦组和非替米沙坦 ARB 组分别有 2280 名和 9120 名患者。替米沙坦组的痴呆诊断风险较低（替米沙坦与非替米沙坦 ARBs：2.19%与 3.20%；HR，0.72；95%CI，0.53 至 0.97；p=0.030）。他们在以 IS 作为竞争风险（亚分布 HR，0.70；95%CI，0.51 至 0.95；p=0.022）和以全因死亡率作为竞争风险（亚分布 HR，0.71；95%CI，0.53 至 0.97；p=0.029）的情况下，痴呆诊断风险也较低。此外，替米沙坦使用者发生任何 IS 的风险较低（6.84%与 8.57%；HR，0.79；95%CI，0.67 至 0.94；p=0.008）。长期随访期间。研究的局限性包括指征残余混杂、观察性研究中因果关系的解释以及使用诊断和药物代码来代表真实临床数据所导致的偏倚。
本研究表明，替米沙坦在东亚人群的高血压 T2DM 患者中的应用可能与痴呆和任何 IS 事件的风险降低有关。
