Can n-of-1 trials of self-selected triggers of atrial fibrillation (AF) improve AF-related quality of life?
In this randomized clinical trial of 466 patients, participating in n-of-1 trials was found not to improve AF-related quality of life but led to fewer subsequent AF episodes compared with controls. No trigger was associated with AF in intention-to-treat analyses; in per-protocol analyses, alcohol heightened the likelihood of AF, whereas other triggers, including caffeine, revealed no relationships with AF.
n-of-1 trigger testing did not enhance AF-related quality of life but reduced the number of AF episodes; alcohol, but not caffeine, increased the risk of AF events.
Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown.
To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life.
Design, Setting, and Participants
A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used bysymptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020.
n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period.
Main Outcomes and Measures
AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing.
Of 446 participants who initiated (mean [SD] age, 58  years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P < .001). In a meta-analysis of the individualized trials, only exposure to alcohol was associated with significantly heightened risks of AF events.
Conclusions and Relevance
n-of-1 Testing of AF triggers did not improve AF-associated quality of life but was associated with a reduction in AF events. Acute exposure to alcohol increased AF risk, with no evidence that other exposures, including caffeine, more commonly triggered AF.
ClinicalTrials.gov Identifier: NCT03323099
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Marcus GM, Modrow MF, Schmid CH, et al. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol. Published online November 14, 2021. doi:10.1001/jamacardio.2021.5010
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