Study links drugs for Alzheimer’s disease with reduced risk of heart attack and death

BMJ 2013; 346 doi: (Published 05 June 2013) Cite this as: BMJ 2013;346:f3669
  1. Ingrid Torjesen
  1. 1London

Patients taking cholinesterase inhibitors for mild to moderate Alzheimer’s disease have been found to have a lower risk of heart attack and death than patients who have never taken the drugs, a Swedish study has found.1

Researchers from Umeå University in Sweden followed 7073 people with Alzheimer’s disease who were on the Swedish Dementia Registry from May 2007 to December 2010. They found that those patients who had been taking cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, had a 36% lower risk of death from any cause than people not taking the drugs: 427 of 5159 (8.3%) who were prescribed a cholinesterase inhibitor at least once died, compared with 329 of 1914 (17.2%) not taking any of these drugs (hazard ratio 0.64 (95% confidence interval 0.54 to 0.76)).

Furthermore, patients with Alzheimer’s disease who were taking cholinesterase inhibitors had a 38% lower risk of a myocardial infarction (74 of 5159 (1.4%) who were prescribed a cholinesterase inhibitor at least once had a myocardial infarction, compared with 42 of 1914 (2.2%) not taking a drug (hazard ratio 0.62 (0.4 to 0.95))) and a 26% reduced risk of death from a cardiovascular causes, such as stroke (hazard ratio 0.74 (0.57 to 0.97)).1

No similar effect was seen in patients taking memantine, a drug indicated for use in moderate to advanced Alzheimer’s disease, which works in a different way to cholinesterase inhibitors.

Peter Nordström, professor of geriatrics at Umeå University, said, “If you translate these reductions in risk into absolute figures, it means that for every 100 000 people with Alzheimer’s disease, there would be 180 fewer heart attacks—295 as opposed to 475—and 1125 fewer deaths from all causes—2000 versus 3125—every year among those taking cholinesterase inhibitors compared to those not using them.”

Patients taking the highest daily recommended doses of cholinesterase inhibitors (donepezil 10 mg, rivastigmine 6 mg, or galantamine 24 mg) were the most protected: their risk of heart attack was 65% lower (hazard ratio 0.35 (0.19 to 0.64)), and their risk of death was 46% lower (hazard ratio 0.54 (0.43 to 0.67)).

Nordström said, “As far as we know, this is the first time that the use of cholinesterase inhibitors has been linked to a reduced risk of heart attacks and deaths from cardiovascular disease in general or from any cause. As this is an observational study, we cannot say that cholinesterase inhibitor use is causing the reduction in risk, only that it is associated with a reduction.”

However, he said that cholinesterase inhibitors were known to have an effect on the vagus nerve, which controls the rate at which the heart beats, and that some experimental studies had indicated that the drugs could also have anti-inflammatory properties.

Nordström said, “Within the atherosclerotic plaque, immune cells produce cytokines that decrease the stability of the plaque, increasing the risk of plaque rupture, and a subsequent myocardial infarction,” he said. Treatment with cholinesterase inhibitors has been shown to reduce peripheral cytokine production in experimental studies and in humans.


Cite this as: BMJ 2013;346:f3669


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