Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial

Abstract

Importance: 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.

Objective: 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 by symptomatic 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.

Interventions: 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.

Results: Of 446 participants who initiated (mean [SD] age, 58 [14] 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.

Trial registration: ClinicalTrials.gov Identifier: NCT03323099.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Marcus reported personal fees and equity interest from InCarda, personal fees from Johnson & Johnson, and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program during the conduct of the study. Drs Modrow, Schmid, and Pletcher reported grants from Patient-Centered Outcomes Research Institute during the conduct of the study. Dr Olgin reported personal fees from AliveCor during the conduct of the study, personal fees from VivaLNK outside the submitted work, and grants from Samsung outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram of Participant Screening, Consent, Randomization, and Study Completion

AV indicates atrioventricular; AFEQT, Atrial Fibrillation Effect on Quality-of-Life; ECG, electrocardiogram. aReasons for ineligibility are not mutually exclusive. bIncludes 1 participant who did not initiate 10-week period.

Figure 2.. Network Meta-analyses Odds Ratios for Self-reported AF During Trigger Exposure vs Avoidance in Intention to Treat and Per Protocol Combining All n-of-1 Trials Throughout the Study

Numbers indicate number of events/number of days reported. AF indicates atrial fibrillation; Crl, credible interval; OR, odds ratio.