Cholinesterase inhibitors and the heart in old age

We found the review by O'Brien & Oyebode (2003) useful in its scope and breadth. It is worth emphasising that many potential cardiovascular side-effects are more likely to occur in old age. Moreover, we would add that the cholinesterase inhibitors, a class of psychotropic medication not mentioned in the review, also have important effects on the cardiovascular system.

Cholinesterase inhibitors slow the degradation of acetylcholine in the synaptic clefts, thus improving the cholinergic deficit that has been a known feature of Alzheimer's dementia (as well as other dementias) for some time (Proctor, 2002). The cardiovascular effects of donepezil, one of the cholinesterase inhibitors, have recently been studied (McLaren et al, 2003). Some of these effects are probably common to this class of drug. The study (n=15) showed that heart rate variability, which is used to assess autonomic function, is impaired by donepezil in people with neurodegenerative dementia. It also revealed a tendency for hypotensive disorders to be exaggerated.

It is known that acetylcholine affects blood pressure and heart rate through both central and peripheral means. Accordingly, some of the cardiovascular effects of cholinesterase inhibition are predictable. Central mechanisms can lead to a rise in blood pressure and a corresponding bradycardia. In patients treated with cholinesterase inhibitors, 7–13% experience peripheral cholinergic side-effects (Nordberg & Svensson, 1998).

In older people, the risk of falls is a major concern. There is evidence that patients with Alzheimer's disease and dementia with Lewy bodies exhibit an unusually high prevalence of orthostatic hypotension and carotid sinus hypersensitivity (Ballard et al, 1998). Cholinergic inhibition is likely to make the tendency to fall greater in these patients (Ballard et al, 1999).

A retrospective study (with the advantage of being naturalistic but without controls) of 160 consecutive patients with dementia treated with cholinesterase inhibitors (Pakrasi et al, 2003) found that 2 patients (1.6%) experienced dysrhythmias and 1 (0.8%) experienced syncope in those treated with donepezil (n=125); 1 patient (11%) treated with galantamine (n=9) had a dysrhythmia; and 1 (3.8%) treated with rivastigmine (n=26) experienced syncope.

Thus, the potential for cholinesterase inhibitors to cause adverse cardiovascular effects and consequently falls and other serious morbidity in older people should not be overlooked.