Economic evaluation of extended electrocardiogram monitoring for atrial fibrillation in patients with cryptogenic stroke.

Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention. Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques. We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke, in comparison to the standard of care. A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the randomized CRYSTAL-AF trial and other published literature. We also conducted scenario analyses (CHADS2 score) and probabilistic sensitivity analyses. All costs and benefits were discounted at 3.5%. Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality-adjusted life years compared to the standard of care (7.37 vs 7.22). Stroke-related costs were reduced in insertable cardiac monitor patients, but overall costs remained higher than the standard of care (£19,631 vs £17,045). The incremental cost-effectiveness ratio was £17,175 per quality-adjusted life years gained, compared to standard of care in the base-case scenario, which is below established quality-adjusted life years willingness-to-pay thresholds. When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy, the incremental cost-effectiveness ratio was £13,296 per quality-adjusted life years gained. Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke. The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes.

BackgroundTo date, insertable cardiac monitors (ICMs) are the most effective method for the detection of occult atrial fibrillation (AF) in cryptogenic stroke. The overall detection rate after 12 months, however, is low and ranges between 12.4 and 33.3%, even if clinical predictors are considered. Ischemic stroke patients due to cardiogenic embolism present with particular lesion patterns. In patients with cryptogenic stroke, MR-imaging pattern may be a valuable predictor for AF.MethodsThis is an MRI-based, retrospective, observational, comparative, single-center study of 104 patients who underwent ICM implantation after cryptogenic stroke. The findings were compared to a reference group with related stroke etiology, i.e., 166 patients with embolic stroke due to AF detected for the first time by long-term ECG. Lesion patterns were evaluated with regard to affected territories, distribution (cortical, lacunar, scattered), lesion volume, and lesion size (diameter of the lesion size > 20 mm).ResultsThe MR-imaging analysis of acute ischemic lesions yielded no association between AF and lesion size or volume, arterial vessel distribution, or the number of affected territories. There was no significant difference between the cohorts regarding ischemic patterns (cortical lesions, scattered lesions, and lacunar infarcts). An important clinical inference of our findings is that 10% (2 of 20) of cases in the ICM group in whom AF was detected had a lacunar infarct pattern. Similar results were shown in cases of ischemic stroke patients with AF detected for the first time by long-term ECG, with 10.9% (16 of 147) of them showing lacunar infarcts. The analysis of chronic MRI lesions revealed no differences between the groups in the rate of chronic lesions, arterial vessel distribution, or the number of affected territories. Left atrial size (LA size) and the presence of atrial runs in long-term ECG were independently associated with AF.ConclusionsIn this MRI-based analysis of patients with cryptogenic stroke who had received ICM implantation, the detection rate of AF in patients with ICM was not related to the imaging pattern. In addition, the lacunar infarct pattern should not be an exclusion criterion for ICM insertion in patients with cryptogenic stroke. ICM insertion in patients with cryptogenic stroke should not be evaluated solely on the basis of reference to infarct patterns.

Objectives: Atrial fibrillation (AF) is the most common arrhythmia and a major marker of ischemic stroke risk. Early detection is crucial and, once diagnosed, anticoagulation therapy can be initiated to reduce stroke risk. The aim of this study was to assess the cost-effectiveness of employing an insertable cardiac monitor (ICM), BIOMONITOR, for the detection of AF compared to standard of care (SoC) ECG and Holter monitoring in patients with cryptogenic stroke, that is, stroke of unknown origin and where paroxysmal, silent AF is suspected.Materials and methods: A Markov model was developed which consisted of five main health states reflecting the potential lifetime evolution of the AF disease: post cryptogenic stroke (index event), subsequent mild, moderate and severe stroke, and death. Sub-states were included to track a patient’s AF diagnostic status and the use of antiplatelet or anticoagulant therapy. AF detection was assumed to result in a treatment switch from aspirin to anticoagulants, except among those with a history of major bleeding. Detection yield and accuracy, clinical actions and treatment effects were derived from the literature and validated by an expert clinician. All relevant costs from a US Medicare perspective were included.Results and conclusions: An ICM-based strategy was associated with a reduction of 37 secondary ischemic strokes per 1000 patients monitored compared with SoC. Total per-patient costs with an ICM were higher (US$90,052 vs. US$85,157) although stroke-related costs were reduced. The use of an ICM was associated with a base-case incremental cost-effectiveness ratio of US$18,487 per life year gained compared with SoC and US$25,098 per quality-adjusted life year gained, below established willingness-to-pay thresholds. The conclusions were found to be robust over a range of input values. From a US Medicare perspective the use of a BIOMONITOR ICM represents a cost-effective diagnostic strategy for patients with cryptogenic stroke and suspected AF.

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IntroductionDetection of atrial fibrillation (AF) is required to initiate oral anticoagulation (OAC) after cryptogenic stroke. However, paroxysmal AF can be difficult to diagnose with short term cardiac monitoring. Taking an...

Introduction: Atrial fibrillation is a known risk factor for the development of stroke. Implantable loop recorders (ILRs) have specific algorithms to detect occult atrial fibrillation and can be used in patients with cryptogenic stroke. There is limited data on the frequency of false positive atrial fibrillation detected by the Medtronic ILR. Hypothesis: Medtronic ILRs have a high rate of false positives but despite this are still effective at detecting atrial fibrillation in patients with cryptogenic stroke. Methods: All stroke patients who underwent ILR placement from Jan 1, 2013 to June 30, 2015 were prospectively collected through an administrative database. Baseline and clinical characteristics were retrospectively obtained. A random sampling of ILR tracings identified as atrial fibrillation by the Medtronic algorithm was adjudicated by a board certified electrophysiologist for accuracy. Results: Among 52 patients with a history of ischemic stroke or TIA (mean age 68±14 years, 58% male, 83% white), there were 166 rhythm strips identified as atrial fibrillation by the Medtronic algorithm which were adjudicated. Of the 166 strips reviewed, 140 (84%) were incorrectly identified as atrial fibrillation; of those false positives, adjudication identified 57% as premature atrial complexes(PACs), 22% as T wave over-sensing, 10% due to noise, 5.0% due to premature ventricular complexes (PVCs), 2.9% due to under-sensing, and 2.9% due to sinus arrhythmia. Of the 38 (73%) patients who had ILR implantation for cryptogenic stroke, 4 (11%) were identified as having true atrial fibrillation by ILR after adjudication over 413 patient-months of monitoring; mean time to atrial fibrillation detection was 93 days after implantation. Conclusions: Stroke patients who undergo Medtronic ILR placement have high false positive rates of atrial fibrillation detected with the Medtronic algorithm. When adequately reviewed by a trained cardiologist for accuracy, the Medtronic ILRs remain effective at detecting atrial fibrillation in cryptogenic stroke patients.

PCV27 COST-EFFECTIVENESS OF INSERTABLE CARDIAC MONITORS VERSUS STANDARD OF CARE OR SHORT-TO-LONG-TERM ECG MONITORING TO IDENTIFY ATRIAL FIBRILLATION AFTER CRYPTOGENIC STROKE

BackgroundCurrent guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out atrial fibrillation. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of atrial fibrillation after cryptogenic stroke has therapeutic implications.MethodsWe conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional follow-up (control) for detecting atrial fibrillation in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of atrial fibrillation (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of atrial fibrillation within 12 months. Data were analyzed according to the intention-to-treat principle.ResultsBy 6 months, atrial fibrillation had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, atrial fibrillation had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001).ConclusionsECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT00924638.)

Recent advancement in digital technology has enabled the development of new portable systems for prolonged electrocardiographic (ECG) monitoring. Implantable loop recorders (ILRs) enable the monitoring of arrhythmias for up to 3 years. Novel non-invasive ECG monitoring devices include handheld monitors, patches, vests, belts, and smartphone-based ECG recorders. These small, portable mobile devices open new horizons of potential lifetime monitoring. Some of these devices are capable of acquiring biosignals other than the ECG, such as respiratory rate, skin temperature, activity level, body position, or geolocation by incorporating GPS systems. Mobile ECG monitoring devices have been evaluated and documented to be useful in several clinical scenarios such as evaluation of symptoms suggestive of arrhythmia, screening for atrial fibrillation in asymptomatic high-risk patients, detection of atrial fibrillation in patients with cryptogenic stroke, or detection of recurrent atrial fibrillation episodes in patients undergoing ablation procedures in post-procedural follow-up.

Background: We assessed cost-effectivenessof insertable cardiac monitors (ICMs) in a US cryptogenic strokepopulation. Materials & methods: We modelled lifetime costs and quality-adjusted life years for three monitoring strategies post cryptogenic stroke: ICM starting immediately, ICM starting after Holter monitoring (delayed ICM)and standard of care involving intermittent ECG and Holter monitoring. Patient characteristics and detection efficacy were based on the CRYSTAL-AF trial. AF detection altered the modelled anticoagulation therapy and subsequent stroke and bleed risks. Results & conclusion: Immediate ICM was found to be cost-effective versus standard of care and cost-saving versus delayed ICM. Results were robust to sensitivity analyses. ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population.

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.

Background: The implantable loop recorder (ILR) is the most sensitive method for detecting atrial fibrillation (AF) following a cryptogenic stroke. However, to date, no study has demonstrated that it significantly reduces the rate of recurrent ischemic stroke. Objective: To assess the cumulative incidence of recurrent ischemic stroke in patients with a prior cryptogenic stroke who received an ILR, and to evaluate whether stroke recurrence is associated with device-detected AF. Methods: We conducted an observational study including consecutive patients with cryptogenic stroke who received an ILR in four academic centres in France. Prior to implantation, all patients underwent a standardized diagnostic workup, including cerebral CT angiography, brain MRI, carotid ultrasound, echocardiography, and at least 24 hours of ECG monitoring. Patients were followed from the date of ILR implantation until the first recurrence of stroke (primary endpoint), death from any cause (competing event), or end of follow-up (defined as ILR explant, last remote transmission, or final device interrogation). Device-detected AF and initiation of oral anticoagulation were analysed as time-dependent covariates in the univariate and multivariate analyses. Cause-specific Cox proportional Hazards model was used as the primary analysis. Results: We included 1,001 patients (median age 68 years [IQR 59–75]; 41% female; median CHA2DS2-VASc score 4 [IQR 3–5]). Over a median follow-up of 1.9 years, 67 recurrent ischemic strokes were recorded, yielding a cumulative incidence of 3.4% per year. ILR-detected AF occurred in 275 patients (27%). In univariate analysis, AF not treated with anticoagulation was associated with a significantly higher risk of recurrent stroke (HR 3.47, 95% CI 1.08–11.11, p=0.037), whereas AF with anticoagulation was not (HR 1.26, 95% CI 0.67–2.34, p=0.473). These associations remained consistent after multivariate adjustment for age, sex, peripheral artery disease, and renal function (HR 3.27, 95% CI 1.01–10.61, p=0.048 for untreated AF; HR 1.01, 95% CI 0.52–1.98, p=0.971 for anticoagulated AF). Conclusion: Among patients with cryptogenic stroke monitored with an ILR, recurrent ischemic stroke remains a significant concern. Device-detected AF is associated with a higher risk of recurrent stroke only when not treated with oral anticoagulation. These findings support early initiation of anticoagulation in patients with device-detected AF to reduce risk of stroke recurrence.

BackgroundTo reduce the risk of thromboembolic complications, clinical guidelines recommend anticoagulation treatment for almost all atrial fibrillation (AF) patients. Although warfarin has long been the primary treatment alternative, now newer alternatives such as apixaban have proven effective in prevention of the thromboembolic complications of non-valvular AF. The aim of this study is to assess the cost–effectiveness of apixaban when compared with warfarin in the prevention of AF-associated thromboembolic complications in Finland.MethodsThe assessment was performed with a lifetime Markov-model with the following health states: non-valvular AF, ischemic stroke, hemorrhagic stroke, other intracranial bleed, other major bleed, clinically relevant non-major bleed, myocardial infarction, and systemic embolism. The treatment efficacies were obtained from the ARISTOTLE trial. Representative Finnish input data were used for the model states, including background mortality, resource use, costs (in 2014 values), and EQ-5D-3L-based quality of life. The results (with 3 % annual discounting) are presented as incremental cost–effectiveness ratios [ICER, cost per quality-adjusted life year (QALY) gained], the expected value of perfect information (EVPI), and the probability of apixaban being cost–effective at various willingness-to-pay levels.ResultsApixaban increased life-expectancy by 0.17 years and quality-adjusted life-expectancy by 0.14 QALYs when compared with warfarin. Additional QALY was gained with apixaban at a cost of 1824 euros based on the deterministic analysis. The maximum EVPI was 649 euros/patient at 1282 euros per QALY gained in the probabilistic analysis. The probability of apixaban being cost–effective reached 80 % when the willingness-to-pay per QALY gained was 14,857 euros. In deterministic sensitivity analyses, ICERs varied from dominance of apixaban to additional QALY being gained at a cost of 12,312 euros.ConclusionsThe ICERs obtained were well below the WHO-CHOICE threshold values for cost–effective interventions, suggesting that apixaban is a very cost–effective treatment alternative for warfarin in Finnish patients with AF.

Introduction: The cause of ischemic stroke remains uncertain (cryptogenic stroke) in 20-40% of cases despite conventional diagnostic tests. Documentation of atrial fibrillation (AF) is required to initiate anticoagulant therapy to reduce recurrent stroke risk, however, the paroxysmal and asymptomatic nature of AF means it is often not detected with traditional monitoring techniques. We assessed the hypothesis that detecting AF via continuous long-term monitoring with an insertable cardiac monitor (ICM) is cost effective for preventing recurrent stroke in cryptogenic stroke patients, in comparison to Standard of Care (SoC). Methods: A randomized controlled trial reported a nine-fold increase in AF detection with an ICM (Reveal XT, Medtronic) compared to SoC over 3 years follow-up, after exclusion of patients with evidence of AF from initial tests. A lifetime Markov model was developed which uses trial data to estimate cost effectiveness of ICM from a U.K. NHS perspective. The CRYSTAL AF study provided AF detection rates, ICM implant complications, resource use and baseline quality of life. Safety and efficacy data for specific non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin were sourced from literature to estimate stroke and bleeding risks. Other quality of life and cost data were sourced mainly from the UK OXVASC study. All costs and benefits were discounted at 3.5% and scenario analyses (CHADS2 score) and probabilistic sensitivity analyses (PSA) were conducted. Results: ICM was associated with fewer recurrent strokes and increased Quality Adjusted Life Years (QALYs) compared to SoC. Stroke-related costs were reduced in the ICM arm, however, overall costs did remain higher than SoC. The incremental cost-effectiveness ratio (ICER) was below a £30,000 per QALY gained willingness-to-pay threshold. Sensitivity analysis indicated that the ICER increased in patients with lower CHADS2 scores, however, it remained below the threshold. Conclusion: AF detection with ICM increases linearly over its 3 year life, identifying AF in nine-fold more patients than SoC. ICM appears to be a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke in the UK and countries with similar healthcare systems.

Detection of atrial fibrillation by implantable loop recorders following cryptogenic stroke: A retrospective study of predictive factors and outcomes