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. 2020 Jan;24(5):1–184. doi: 10.3310/hta24050

Implantable cardiac monitors to detect atrial fibrillation after cryptogenic stroke: a systematic review and economic evaluation.

Steven J Edwards, Victoria Wakefield, Tracey Jhita, Kayleigh Kew, Peter Cain, Gemma Marceniuk
PMCID: PMC6983910  PMID: 31944175

Abstract

BACKGROUND

Cryptogenic stroke is a stroke for which no cause is identified after standard diagnostic tests. Long-term implantable cardiac monitors may be better at diagnosing atrial fibrillation and provide an opportunity to reduce the risk of stroke recurrence with anticoagulants.

OBJECTIVES

The objectives were to assess the diagnostic test accuracy, clinical effectiveness and cost-effectiveness of three implantable monitors [BioMonitor 2-AF™ (Biotronik SE & Co. KG, Berlin, Germany), Confirm Rx™ (Abbott Laboratories, Lake Bluff, IL, USA) and Reveal LINQ™ (Medtronic plc, Minneapolis, MN, USA)] in patients who have had a cryptogenic stroke and for whom no atrial fibrillation is detected after 24 hours of external electrocardiographic monitoring.

DATA SOURCES

MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effects and Health Technology Assessment databases were searched from inception until September 2018.

REVIEW METHODS

A systematic review was undertaken. Two reviewers agreed on studies for inclusion and performed quality assessment using the Cochrane Risk of Bias 2.0 tool. Results were discussed narratively because there were insufficient data for synthesis. A two-stage de novo economic model was developed: (1) a short-term patient flow model to identify cryptogenic stroke patients who have had atrial fibrillation detected and been prescribed anticoagulation treatment (rather than remaining on antiplatelet treatment) and (2) a long-term Markov model that captured the lifetime costs and benefits of patients on either anticoagulation or antiplatelet treatment.

RESULTS

One randomised controlled trial, Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL-AF) (Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:2478-86), was identified, and no diagnostic test accuracy study was identified. The CRYSTAL-AF trial compared the Reveal™ XT (a Reveal LINQ predecessor) (Medtronic plc) monitor with standard of care monitoring. Twenty-six single-arm observational studies for the Reveal devices were also identified. The only data for BioMonitor 2-AF or Confirm Rx were from mixed population studies supplied by the companies. Atrial fibrillation detection in the CRYSTAL-AF trial was higher with the Reveal XT than with standard monitoring at all time points. By 36 months, atrial fibrillation was detected in 19% of patients with an implantable cardiac monitor and in 2.3% of patients receiving conventional follow-up. The 26 observational studies demonstrated that, even in a cryptogenic stroke population, atrial fibrillation detection rates are highly variable and most cases are asymptomatic; therefore, they probably would not have been picked up without an implantable cardiac monitor. Device-related adverse events, such as pain and infection, were low in all studies. The de novo economic model produced incremental cost effectiveness ratios comparing implantable cardiac monitors with standard of care monitoring to detect atrial fibrillation in cryptogenic stroke patients based on data for the Reveal XT device, which can be related to Reveal LINQ. The BioMonitor 2-AF and Confirm RX were included in the analysis by making a strong assumption of equivalence with Reveal LINQ. The results indicate that implantable cardiac monitors could be considered cost-effective at a £20,000-30,000 threshold. When each device is compared incrementally, BioMonitor 2-AF dominates Reveal LINQ and Confirm RX.

LIMITATIONS

The cost-effectiveness analysis for implantable cardiac monitors is based on a strong assumption of clinical equivalence and should be interpreted with caution.

CONCLUSIONS

All three implantable cardiac monitors could be considered cost-effective at a £20,000-30,000 threshold, compared with standard of care monitoring, for cryptogenic stroke patients with no atrial fibrillation detected after 24 hours of external electrocardiographic monitoring; however, further clinical studies are required to confirm their efficacy in cryptogenic stroke patients.

STUDY REGISTRATION

This study is registered as PROSPERO CRD42018109216.

FUNDING

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 5. See the NIHR Journals Library website for further project information.

Plain language summary

An abnormal heart rhythm (atrial fibrillation) is an important cause of stroke. Clots form in the heart, break off, pass into blood vessels in the head and block the blood supply to parts of the brain. This is important to diagnose because atrial fibrillation can be treated with blood-thinning drugs, which can prevent further stroke. For this reason, all patients with stroke are tested for atrial fibrillation. Unfortunately, the standard tests, which include 24 hours of outpatient external heart monitoring, may miss the condition. Implantable cardiac monitors, which are small devices placed beneath the skin of the chest that can monitor the heart for up to 4 years, may be better than the standard tests. This study compared three different implantable cardiac monitors [BioMonitor 2-AF™ (Biotronik SE & Co. KG, Berlin, Germany), Confirm Rx™ (Abbott Laboratories, Lake Bluff, IL, USA) and Reveal LINQ™ (Medtronic plc, Minneapolis, MN, USA)] to determine how effective they are at detecting atrial fibrillation in people who have had a cryptogenic stroke (a stroke for which no cause is identified), whether or not they are better than standard monitoring and whether or not they offer good value for money. No evidence was found that directly compared the three implantable monitors in cryptogenic stroke patients. The limited evidence found suggested that all three monitors had few side effects; only one monitor (Reveal LINQ) had evidence that it was better than standard monitoring. By 36 months, 19% of patients had atrial fibrillation detected by Reveal LINQ compared with only 2.3% with conventional monitoring. There was insufficient information for the other monitors. Overall, implantable monitors offer value for money when compared with standard monitoring for people who have had a cryptogenic stroke and for whom atrial fibrillation has not been detected with standard tests.

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