Cholinesterase inhibitors are commonly used to treat dementia. These drugs enhance the effects of acetylcholine, and reports suggest they may precipitate bradycardia in some patients. We aimed to examine the association between use of cholinesterase inhibitors and hospitalization for bradycardia.
We examined the health care records of more than 1.4 million older adults using a case-time-control design, allowing each individual to serve as his or her own control. Case patients were residents of Ontario, Canada, aged 67 y or older hospitalized for bradycardia between January 1, 2003 and March 31, 2008. Control patients (3:1) were not hospitalized for bradycardia, and were matched to the corresponding case on age, sex, and a disease risk index. All patients had received cholinesterase inhibitor therapy in the 9 mo preceding the index hospitalization. We identified 1,009 community-dwelling older persons hospitalized for bradycardia within 9 mo of using a cholinesterase inhibitor. Of these, 161 cases informed the matched analysis of discordant pairs. Of these, 17 (11%) required a pacemaker during hospitalization, and six (4%) died prior to discharge. After adjusting for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor (adjusted odds ratio [OR] 2.13, 95% confidence interval [CI] 1.29-3.51). The risk was similar among individuals with pre-existing cardiac disease (adjusted OR 2.25, 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34, 95% CI 1.16-4.71). We found no such association when we replicated the analysis using proton pump inhibitors as a neutral exposure. Despite hospitalization for bradycardia, more than half of the patients (78 of 138 cases [57%]) who survived to discharge subsequently resumed cholinesterase inhibitor therapy.
Among older patients, initiation of cholinesterase inhibitor therapy was associated with a more than doubling of the risk of hospitalization for bradycardia. Resumption of therapy following discharge was common, suggesting that the cardiovascular toxicity of cholinesterase inhibitors is underappreciated by clinicians.
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Cites: CMAJ. 2000 May 16;162(10):1421-410834045
Cites: Drug Saf. 2007;30(11):1063-7117973542
Cites: Annu Rev Public Health. 2000;21:193-22110884952
Cites: Arch Intern Med. 2001 Jun 11;161(11):1405-1011386889
Cites: Pharmacoepidemiol Drug Saf. 2001 May;10(3):259-6211501340
Cites: JAMA. 2007 Dec 12;298(22):2634-4318073359
Cites: Epidemiology. 2008 Jan;19(1):30-718091000
Cites: Ann Intern Med. 2008 Mar 4;148(5):370-818316755
Cites: Ann Intern Med. 2008 Mar 4;148(5):379-9718316756
Cites: Neurology. 2008 May 27;70(22):2024-3518322263
Cites: Stat Methods Med Res. 2009 Feb;18(1):67-8018562398
Cites: Arch Intern Med. 2009 May 11;169(9):867-7319433698