Some antihypertensive meds tied to lower dementia risk

Calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) may be associated with a reduced risk of dementia, according to a systematic review and network meta-analysis conducted by researchers from the Netherlands.

The researchers reviewed 15 observational studies and seven randomized controlled trials (RCTs) comprising 649,790 individuals (median age 74 years) who had been receiving antihypertensive medications for >1 year. After a median follow-up period of 4.3 years, 3.02 percent (n=19,600) were diagnosed with dementia.

Review of the observational studies showed that CCBs were associated with a reduced risk of dementia compared with angiotensin-converting enzyme (ACE) inhibitors (hazard ratio [HR], 0.84, 95 percent confidence interval [CI], 0.74–0.95), beta blockers (HR, 0.83, 95 percent CI, 0.73–0.95), and diuretics (HR, 0.89, 95 percent CI, 0.78–1.01). [AAIC 2020, abstract ODO4-08-06]

The risk of dementia was also lower with use of ARBs compared with ACE inhibitors (HR, 0.88, 95 percent CI, 0.81–0.97), beta blockers (HR, 0.87, 95 percent CI, 0.77–0.99), and diuretics (HR, 0.93, 95 percent CI, 0.83–1.05).

“[T]he use of CCBs was associated with a 16–17 percent risk reduction and the use of ARBs with a 12–13 percent risk reduction in dementia incidence compared with beta blockers and ACE inhibitors,” said Dr Melina den Brok from Radboud University Medical Center, Nijmegen, the Netherlands, who presented the results at AAIC 2020.

“Recommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia,” she said.

Den Brok noted that the small number of RCTs rendered less robust results and precluded conclusions from being drawn on these associations. “[Nonetheless,] if confirmed in a randomized setting, CCBs and ARBs as standard therapy for hypertension may be a low-cost and easy to implement prevention strategy to reduce the risk of dementia globally,” she concluded.

Candesartan improves cognition in patients with MCI

A separate study on older individuals with mild cognitive impairment (MCI)* suggested that the ARB candesartan had a better effect on cognition than the ACE inhibitor lisinopril.

Participants in the phase 2 CALIBREX** study were 176 individuals aged ≥55 years with MCI and hypertension. Their ongoing antihypertensive therapy was initially withdrawn, and they were randomized to receive increasing doses of candesartan (up to 32 mg/day) or lisinopril (up to 40 mg/day). If required, antihypertensive treatments were added to achieve a target blood pressure (BP) of <140/90 mm Hg. BP control was comparable between groups during the trial.

Assessment of the 141 patients included (mean age 65 years, 55 percent female) showed that at 12 months, executive function, based on Trail Making Test Parts A and B (TMT, B-A), improved in candesartan recipients and worsened in lisinopril recipients (-16.8 vs 11.5 seconds; p=0.008). [AAIC 2020, abstract ODO3-06-06]

There was a greater improvement in delayed recall, assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R), with candesartan vs lisinopril (difference, 1.0 vs 0.3; p=0.026). Microvascular brain injury, assessed as change in white matter lesion volume, did not significantly change with candesartan (0.2 mm³), though lisinopril recipients experienced an increase (0.9 mm³; p=0.06).

“Candesartan demonstrates superior cognitive outcomes compared to lisinopril and may offer unique neurocognitive protection in older adults with executive MCI and hypertension,” said the researchers.

“These effects were independent of but likely additive to BP-lowering properties,” presented Associate Professor Ihab Hajjar from the Emory University School of Medicine, Atlanta, Georgia, US, who noted that the findings require confirmation in larger studies.