Associations of antihypertensive medication (AHM) consumption and drug‐drug interaction with Statin and Metformin with reduced Alzheimer’s disease and related dementias (ADRD) risk among hypertensive patients with mild cognitive impairment (MCI) using high volume claims data

Abstract

AbstractBackgroundWhile hypertension is a modifiable risk factor of Alzheimer’s disease and related dementias (ADRD), limited studies have been conducted on drug effectiveness of antihypertensive medications (AHMs) on ADRD progression from mild cognitive impairment (MCI) or on drug‐drug interactions of AHMs with drugs for other risk factors such as type 2 diabetes and hypercholesterolemia.Method128,683 unique hypertensive patients with MCI on US‐based Optum claims data were identified. Diuretics, beta blockers (BBs), calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACE inhibitors), and angiotensin II receptor antagonists (ARBs) were identified as five major AHM classes. Baseline characteristics were compared. Cox proportional hazards (PH) models were used to study the association between specific AHM exposure and the progression from MCI to ADRD while controlling for demographic variables, comorbidities, and use of Statin and Metformin. To examine the association of AHM‐Statin or AHM‐Metformin interaction with ADRD progression, we also investigated models controlling for aforementioned confounders, as well as drug‐drug interaction terms.ResultThe study included 100,678 patients who were taking at least one class of AHM and 28,005 who were not taking any AHMs. AHM users had higher ratios for the comorbidities (all P≤0.039) and consumption of Metformin and Statin (both P<0.001) compared to non‐users. Users of each major AHM class showed significantly lower risk of developing ADRD compared to non‐users of that specific drug class (adjusted hazard ratio (aHR): 0.96‐0.98; all P≤0.048). Within patients on monotherapy (using only one AHM drug), no specific AHM class had significantly lower risk of ADRD diagnosis compared to other AHM drug classes (aHR: 0.97‐1.11; all P≥0.053). Use of Diuretics or CCBs in combination with Metformin consumption (aHR: 0.89, 0.91, respectively) showed lower risk of MCI to ADRD progression than that under Metformin non‐consumption (aHR: 0.97, 0.98), whereas use of any of the five major AHMs under Statin consumption (aHR: 0.91‐0.94) all showed lower risk than that under Statin non‐consumption (aHR: 0.98‐1.04).ConclusionAll five major AHM classes show a protective effect against ADRD progression among hypertensive patients with MCI. Also, AHMs combined with consumption of Metformin or Statin showed a stronger protective effect compared to non‐consumption.