Centrally Active ACEIs and Cognitive Decline—Reply

In reply

We thank Asamura and colleagues for their letter and agree that physicians should consider tissue distribution when selecting an ACEI. Todd and colleagues point out that the intervention in the PROGRESS trial was perindopril based and for some participants also included indapamide. However, this was a placebo-controlled trial and 2561 participants were randomized to single therapy with perindopril or placebo, thus allowing a direct comparison to be made. In that subgroup analysis, there was a 15% risk reduction for cognitive decline in the perindopril group, though it did not reach statistical significance.¹ We agree with Todd and colleagues that there are still many questions to be answered in the connection between hypertension and cognitive impairment or dementia and specific antihypertensive regimens and agree that designing studies of hypertension treatment powered on the primary outcome of cognition is an important next step, as we highlighted in our discussion.² In the meantime, when starting an ACEI therapy for hypertension, clinicians might consider preferentially using one that crosses the BBB.