Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: A population-based cohort study

PLoS Med. 2021 Jul 19;18(7):e1003707. doi: 10.1371/journal.pmed.1003707. eCollection 2021 Jul.

Abstract

Background: 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.

Methods and findings: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Asian People
  • Cohort Studies
  • Dementia / epidemiology*
  • Dementia / prevention & control*
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Humans
  • Hypertension / complications*
  • Hypertension / drug therapy*
  • Male
  • Taiwan / epidemiology
  • Telmisartan / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Telmisartan

Grants and funding

CHL was supported by the Ministry of Science and Technology grant MOST 108-2314-B-182A-050 -MY1-3 and the Chang Gung Memorial Hospital Research Project (CMRP) grant CMRPG3F, CFRPG3L0011, and BMRPF99. THC and the Maintenance Project at the Biostatistical Consultation Center at Chang Gung Memorial Hospital were supported by the CMRP grant CLRPG2C0021, CLRPG2C0022, CLRPG2C0023, CLRPG2C0024, and CLRPG2G0081. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.