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Alzheimer’s drugs may reduce MI risk
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Cholinesterase inhibitor use for the treatment of Alzheimer’s disease was associated with a significantly reduced risk for myocardial infarction and death in a large Swedish cohort, researchers reported.
Cholinesterase inhibitors (ChEIs), including donepezil, rivastigmine and galantamine, are indicated for mild to moderate Alzheimer’s disease, and experimental studies have shown they have a beneficial effect on the vagus nerve resulting in improved cardiac function, as well as anti-inflammatory properties.
Peter Nordström, MD, of Umeå University in Sweden, and colleagues followed 7,073 patients (median age, 79 years) enrolled in the Swedish Dementia Registry with diagnoses of Alzheimer’s dementia or Alzheimer’s mixed dementia from May 2007 through December 2010. The researchers used national registers to link diagnosed myocardial infarctions (MIs) and death to ChEI use.
Peter Nordström
Adjusting for confounders, including age, sex and the type of Alzheimer’s disease, investigators found that patients taking ChEIs had a 36% (HR=0.64; 95% CI, 0.54-0.76) lower risk for death from any cause, a 38% (HR=0.62; 95% CI, 0.40-0.95) reduced risk for MI, and a 26% (HR=0.74; 95% CI, 0.57-0.97) reduced risk for death from cardiovascular causes.
“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 and 1,125 fewer deaths from all causes every year among those taking ChEIs compared to those not using them,” Nordström said in a press release.
Patients who received the highest recommended doses (donepezil, 10 mg; rivastigmine, >6 mg; galantamine, 24 mg) had the lowest risk for MI (HR=0.35; 95% CI, 0.19-0.64) and death (HR=0.54; 95% CI, 0.43-0.67).
The researchers also examined whether the reduction in risk was associated with the NMDA-receptor antagonist memantine, which is indicated for moderate to advanced Alzheimer’s disease. Further analyses, however, indicated that memantine use had no influence on the risk for MI or death.
The mechanisms of action underlying the cardiovascular effects of ChEI use are only speculative at this point, the researchers said. They did note that vagal nerve stimulation was an interesting candidate.
Nordström said the results need to be confirmed by additional studies before any clinical recommendations of ChEIs can be made in relation to CVD.
“As far as we know, this is the first time that the use of ChEIs has been linked to a reduced risk of heart attacks and deaths from cardiovascular disease in general or from any cause,” he said. “As this is an observational study, we cannot say that ChEI use is causing the reduction in risk, only that it is associated with a reduction. However, the strengths of the associations make them very interesting from a clinical point of view, although no clinical recommendations should be made on the basis of the results from our study.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Judy Willis, MD, MEd
The research described in the study by Peter Nordstrom et al is very good news for neurologists. It supports our continued use of the mainstay class of treatments for Alzheimer’s disease, the cholinesterase inhibitors (ChEIs).
It will be the purview of cardiologists to follow the findings in this observational study regarding strong associations with the use of ChEIs and reduced risk for MI and death. For neurologists, the clinical implications are that this class of drugs appears to have cardiac benefits and is not linked to evidence of cardiotoxicity, such that it might be pulled from our use.
We’ve seen the loss of very useful NSAIDS after years of helping patients when they were subsequently found to carry the risk for adverse cardiovascular events. Again, after decades of use of all propoxyphene-containing medications for pain treatment, this class of medications was also pulled for rare, but “potentially serious,” cardiac arrhythmias.
This study increases our confidence in the continued safe use of the potent group of ChEIs and their significant benefits to many of our Alzheimer’s disease patients, as well as their families.
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