In Alzheimer's, Not All ACE Inhibitors Are the Same

Summarized by Robert W. Griffith, MD
November 10, 2004

Introduction

When considering different drugs, it's customary to classify them in groups - beta-blockers, ACE inhibitors, NSAIDs, statins, and so on. And enthusiasts for 'therapeutic substitution' - replacing one drug of a class with another that may be cheaper - support the classification process. But, now and then, reports emerge showing that within a single drug class, big differences can occur. Usually this involves an increased risk of a particular side effect; for instance, cases of myositis with cerivastatin led to its withdrawal, whereas the other statins can cause this effect, but only extremely rarely.

A Japanese study with various ACE inhibitors shows that differences occur within the class, depending on whether they can cross the blood-brain barrier and thereby affect the course of Alzheimer's disease. The relevant publication in Neurology is summarized here.

What was done

Patients eligible for the study were those over 65 with mild to moderate Alzheimer's and a raised blood pressure (over 140/90 mm Hg). They had to be otherwise healthy, and have a negative brain MRI to exclude 'vascular dementia'. After screening, 162 patients were enrolled to receive medication for their high blood pressure: either a brain-penetrating ACE inhibitor, a non brain-penetrating ACE inhibitor, or a calcium blocker.¹ The drugs were allocated to the patients randomly, as they all had similar blood-pressure lowering properties.

The only other drugs allowed during the study were donepezil (a cholinesterase inhibitor used in mild to moderate Alzheimer's), statins, and aspirin.

The Mini-Mental State Examination (MMSE) was administered at baseline and at the end of the 12-month study, to assess the status of their Alzheimer's.

What were the results?

The average age of the patients was 76, and 78% of them were women. All three treatment groups had satisfactory blood pressure control, with systolic levels brought to 132 mm Hg or below.

The MMSE scores showed a clear-cut deterioration in their Alzheimer's in the non brain-penetrating ACD inhibitor and calcium-channel blocker groups, whereas the brain-penetrating ACE inhibitor patients had no such deterioration. There were no side effects of treatment reported.

What does this study show?

An editorial in the same issue of Neurology points out a number of flaws in the study design (and the report) that makes it difficult to accept the findings without question.² The study was not 'blinded' (so that both the patients and the treating doctors were unaware of which drugs the patients were given), the results for the peridopril and captopril patients are not given separately, and the amount of deterioration in Alzheimer's over 12 months for the other two groups was larger than expected from other studies.

The findings, however, receive support from a large clinical study describing a reduced incidence of dementia in patients taking perindopril and indapamide (a 'water-pill' or diuretic) together.³

Based on these two studies, it seems reasonable that, if the doctor is going to prescribe an ACE inhibitor for high blood pressure in a patient with mental deterioration, the choice should probably be perindopril or captopril, rather than one of the other drugs of this class.

The Japanese study is a further reminder that not all drugs in the same class are equal, both when it comes to ill-effects (side effects) and beneficial effects.

Source

• Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. T. Ohrui, N. Tomita, T. Sato-Nakagawa,  et al., Neurology, 2004, vol. 63, pp. 1324--1325

Footnotes
1. The brain-penetrating ACE inhibitors used were perindopril or captopril, the non brain-penetrating ACE inhibitors were enalapril or imidapril, and the calcium-channel blockers were nifedipine or nilvadipine.
2. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression: A handful of ACEs? D. Knopman, Editorial. Neurology, 2004, vol. 63, pp. 1145--
3. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. C. Tzourio, C. Anderson, N. Chapman,  et al., Arch Intern Med, 2003, vol. 163, pp. 1069--1075

Related Links
Amino-Acid Tied to Alzheimer's Risk
Statins to Stop Dementia?
Diabetes, High Blood Pressure and Mild Mental Decline

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