Comparison Of First Line Antihypertensive Agents And The Risk Of Dementia In Adults With Hypertension: A Real-world Evidence Cohort Study

• By: ADESUYAN, Matthew (Ucl School Of Pharmacy, United Kingdom)
• Co-author(s): Mr Matthew Adesuyan (University College London, London, United Kingdom)
  
• Abstract:

  Background Information
  Dementia represents a global epidemic with no treatment to slow neurodegeneration. Hypertension is a recognized modifiable risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of dementia is inconclusive.
  Purpose
  The objective of this study was to evaluate the association between first-line treatment with angiotensin II receptor blockers (ARB), beta-adrenergic receptor antagonists (BB), calcium channel blockers (CCB) or thiazide-diuretics compared with angiotensin converting enzyme inhibitors (ACEI) and the risk of incident dementia.
  Method
  Primary care health records from IQVIA Medical Research Data (IMRD-UK) were used to conduct a new-user active comparator cohort study in adults ≥40 years with a new diagnosis of hypertension and newly initiated on one of five antihypertensive agents (ACEI, ARB, BB, CCB or thiazide-diuretics) between 2000-2021 in the UK. We excluded participants with a prior diagnosis of dementia, cognitive impairment, confusion, prescription for treatment of dementia symptoms or prior antihypertensive therapy use. Validated diagnostic read codes linked to a clinical diagnosis were used to measure the outcome of dementia. To address the latency of dementia development, follow-up was started 1 year after initiation of antihypertensive therapy. Potential confounders including blood pressure, underlying health conditions, co-prescribed medicines, socioeconomic status and lifestyle factors (e.g. BMI, smoking and alcohol) were adjusted using inverse probability of treatment weighting (IPTW) based on propensity scores. The relative risk of dementia was estimated using a Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (CI).
  Results
  The study cohort included 733,151 hypertensive patients with a mean age of 64 (SD 12) years and 53% female sex; 202,716 initiated on an ACEI, 35,305 ARB, 164,143 BB, 158,810 CCB, and 172,177 thiazide-diuretics. A total of 28,912 cases of newly diagnosed dementia occurred during a median follow-up of 7.4 (IQR 3.2-11.4) years. After IPTW, all measured covariates were well balanced between each antihypertensive drug class and ACEI (reference group). ARB and BB initiators were associated with a lower risk of dementia compared to ACEI initiators; HR 0.91 (95%CI, 0.86-0.97) and 0.93 (95%CI, 0.89-0.97) respectively. There was no evidence of reduced risk in those who initiated CCB or thiazide-diuretics compared to ACEI initiators; HR 0.99 (95%CI, 0.96-1.03) and 0.98 (95%CI, 0.95-1.02) respectively.
  Conclusion
  In adults newly diagnosed with hypertension, initiation with angiotensin II receptor blockers or beta-blockers was associated with a lower risk of dementia compared to those initiated with angiotensin converting enzyme inhibitors. There was no difference in risk of dementia when initiated on calcium channel blockers or thiazide-diuretics. These findings may help patients and prescribers when choosing antihypertensive therapy in those at an increased risk of dementia. We were unable to account for ethnicity, which is a determinant of first line antihypertensive use and risk factor for dementia. To improve the generalisability of our findings, a randomised controlled trial that includes participants from various ethnic backgrounds would be beneficial to confirm the findings of this study.