Comparative Effectiveness of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Risk of Dementia in Patients with Type 2 Diabetes and Hypertension



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Objectives: Specific aims of the study were: (1) To develop RxDx risk index to predict dementia in patients with type 2 diabetes mellitus and hypertension (2) To compare RxDx risk index with different versions of Charlson comorbidity score (CCS) and chronic disease score (CDS) to predict dementia and (3) To compare Angiotensin Converting Enzyme (ACE) inhibitors versus Angiotensin Receptor Blockers (ARB) for the risk of dementia in patients with type 2 diabetes mellitus and hypertension. Methods: The Clinical Practice Research database was used for this retrospective longitudinal cohort study. Elderly patients (age>=65 years) diagnosed with type 2 diabetes and hypertension without prior diagnosis for dementia were included in the cohort. The Cox proportional hazard model was constructed to model time to dementia by incorporating age, gender and 31 RxDx disease conditions. Points were assigned to risk factors based on beta coefficients to obtain summary risk score. Different rick indices were compared against RxDx-Dementia risk index using c statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A marginal structural model was constructed while controlling for demographic and clinical baseline variables and time-varying blood pressure variable to estimate causal effect of ACE inhibitors compared to ARB on the risk of dementia. Results: The incidence of dementia was 3.42% in patients with type 2 diabetes mellitus and hypertension. The c-statistics value for RxDx-Dementia risk index was 0.795 (95% confidence interval [CI], 0.789-0.801) and 0.806 (95% CI, 0.798-0.814). Based on the c-statisctics, NRI and IDI values the RxDx-Dementia risk index performed better compared to summary CCS, CDS scores and its combinations. The marginal structural model estimated statistically significant 39% (OR, 0.61; 95%CI, 0.50-0.77) reduction in the risk of developing dementia compared to ACE inhibitors. Conclusions: RxDx-Dementia risk index can be a useful tool to identify hypertensive diabetic patients who are at high risk of developing dementia as well as to control confounding in observational studies. ARB may offer protective effect on the risk of dementia compared to ACE inhibitors in patients with type 2 diabetes and hypertension. When there is no treatment available for dementia, prevention or delaying onset of dementia may help reduce the overall disease burden.



Hypertension, Diabetes, Dementia, Confounding, RxDx risk index, Comparative effectiveness, Angiotensin converting enzyme (ACE) inhibitors, Angiotensin receptor blockers (ARB)