Patients who used cholinesterase inhibitors had a 38% lower risk of heart attacks, based on a study of Swedish Alzheimer’s disease patients published online June 4 in the European Heart Journal.
"This is an observational study, [so] we cannot say that cholinesterase inhibitor use is causing the reduction in risk, only that it is associated with a reduction. It would be of great value if a meta-analysis of previous, randomized controlled trials could be performed, as this might produce answers on which clinical recommendations could be based," lead investigator Dr. Peter Nordstrom, of Umea University in Sweden, said in a statement.
The findings were not adjusted for statin use, which was unknown.
The investigators cross-linked the records of 7,073 patients in the Swedish Dementia Registry to myocardial infarction and death records in national registries. The results were then adjusted for age, gender, weight, height, dementia type, living conditions, home care, cognitive function, cardiovascular disease history, baseline health, and the use of antidepressants, neuroleptics, antihypertensives, and antidiabetics.
Compared with 1,914 Alzheimer’s patients who never took cholinesterase inhibitors, the 5,159 patients who used the drugs during a mean period of 495 days had a 38% lower risk of myocardial infarction (hazard ratio, 0.62; 95% confidence interval, 0.40-0.95), a 34% lower risk of MI or death (HR, 0.66; 95% CI, 0.56-0.78), a 26% lower risk of death from all cardiovascular causes (HR, 0.74; 95% CI, 0.57-0.97), and a 36% lower risk of death from any cause (HR, 0.64; 95% CI, 0.54-0.76). A case-control analysis produced similar results (Eur. Heart J. 2013 June 4 [doi: 10.1093/eurheartj/eht182]).
Patients who, in their last recorded prescription, were taking higher doses of cholinesterase inhibitors – 10 mg of donepezil, 24 mg of galantamine, or more than 6 mg of rivastigmine daily – had the lowest risk of MI (HR, 0.35; 95% CI, 0.19-0.64) and death (HR, 0.54; 95% CI 0.43-0.67). Among those with baseline cardiovascular disease, high doses of cholinesterase inhibitors reduced MI risk by 71% (HR, 0.29; 95% CI, 0.09-0.94).
Memantine, an Alzheimer’s drug with a different mechanism, was not associated with lower rates of death.
"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 1,125 fewer deaths from all causes – 2,000 versus 3,125 – every year among those taking cholinesterase inhibitors compared to those not using them," Dr. Nordstrom said in a statement.
If cholinesterase inhibitors really do protect the heart, it might have something to do with their known anti-inflammatory properties or their effects on the vagus nerve, the investigators noted.
The subjects were enrolled in the Swedish Dementia Registry between May 2007 and December 2010 with newly diagnosed Alzheimer’s disease. Their mean age was 79 years at baseline, about 60% were women, and 831 had an MI or died.
The investigators reported no conflicts of interest. The Swedish Research Council, the Swedish Association of Local Authorities and Regions, and other groups paid for the work.