Current Attitudes towards Oral Anticoagulant Use to Treat Cardiac Device Patients with Subclinical Atrial Fibrillation: Results from a Four‐Nation Physician Survey

DOI: 10.19102/icrm.2015.060405

¹KARAN BAMI, MD, ²JENS COSEDIS NIELSEN, MD, DMSc, PhD, ³MARCO ALINGS, MD, PhD, ⁴DAVID CONEN, MD, MPh, ⁵ATUL VERMA, MD, ⁶DAVID BIRNIE, BSc (Hons), MD, ChB, MRCP(UK), MD, ⁷FRANCOIS PHILIPPON, MD, ⁸DEREK V. EXNER, MD, MPH, FHRS, ¹STUART J. CONNOLLY, MD, FRCP, ¹CARLOS A. MORILLO, MD, FRCP and ¹JEFF S. HEALEY, MD, FRCP

¹Population Health Research Institute, McMaster University, Hamilton, Canada

²Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark

³Amphia Ziekenhuis, Breda, the Netherlands

⁴Department of Medicine, University Hospital, Basel, Switzerland

⁵Heart Rhythm Program, Division of Cardiology, Newmarket, Canada

⁶University of Ottawa Heart Institute, Ottawa, Canada

⁷Institut Universitaire de cardiologie et de pneumologie de Québec, Québec, Canada

⁸Libin Cardiovascular Institute of Alberta, Calgary, Canada

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ABSTRACT. Device‐detected subclinical atrial fibrillation (SCAF) of at least 6 min in duration is associated with an increased risk of stroke. However, the temporal relationship between SCAF and stroke is not consistent and there is no evidence to show a reduction in stroke with the use of oral anticoagulation (OAC) in patients with SCAF. We conducted a survey of 181 physicians caring for pacemaker and implantable cardioverter‐defibrillator patients in four countries to assess their attitudes towards the use of OAC for stroke prevention in SCAF. A total of 91 surveys (50%) were completed. Half of the centers (52%) reported that physicians are routinely called to assess patients with SCAF, and 47% have a system in place to stratify risk and treat patients with SCAF. Only 19% report using OAC for most patients with SCAF, while 91% state that they would be willing to enroll patients into a trial evaluating OAC in this population, with little variation between countries: Canada 94%, the Netherlands 81%, Switzerland 81%, and Denmark 100%. Of physicians who would participate in a clinical trial, 45% would be willing to enroll patients with a history of stroke >6 months before enrollment, while only 36% would enroll patients with a stroke in the prior 6 months. Among patients with a CHADS2 score of ≥2, 75% of physicians would enroll patients with an episode of SCAF up to 6 h in duration, while 49% of physicians would enroll patients with SCAF of more than 48 h. There is extensive variation in attitudes towards the use of OAC to treat SCAF. The majority of surveyed physicians expressed equipoise as to whether the potential risk of SCAF mandates the use of OAC.

KEYWORDS. anticoagulation, cardiac implantable electronic device, subclinical atrial fibrillation.

The authors have reported the following: Jens Cosedis Nielsen – Research grant from Biosense Webster; Marco Alings – Research grants from St. Jude Medical, Boston Scientific, and Medtronic; Francois Philippon – Research grants from Medtronic, Boston Scientific, and St. Jude Medical; Derek Exner – Research grants and consulting ‐ Medtronic, St. Jude Medical and Analytics for Life; Jeff S. Healey – Research grants and speaking fees from Medtronic, St. Jude Medical, Bayer, Boehringer‐Ingelheim and Bristol‐Meyers‐Squibb. Dr. Healey has a personnel award from the Heart and Stroke Foundation, Ontario Provincial office (MC7450).
Manuscript received January 12, 2015, final version accepted January 29, 2015.

Address correspondence to: Karan Bami, MD, Department of Medicine, The Ottawa Hospital – Civic Campus. 407A – 737 Parkdale Ave. Ottawa, ON, K1Y1J8.

E-mail: karan.bami@medportal.ca

Introduction

There are more than 400,000 pacemakers and implantable cardioverter‐defibrillators (ICDs) implanted each year in North America alone.^1–3 Most newly implanted cardiac devices include an atrial lead and permit the identification of short‐lasting, asymptomatic atrial arrhythmias that would otherwise go undetected.^4–6 The ASymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial (ASSERT) and A Prospective study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics (TRENDS) trials have shown that device‐detected subclinical atrial fibrillation (SCAF) is very common and is associated with a two‐ to threefold increase in the risk of stroke.^6,7 However, there is currently no consensus on the use of oral anticoagulation (OAC) therapy to treat patients with SCAF, and recent guidelines state that there is insufficient evidence to recommend OAC for most patients with SCAF of less than 24‐h duration.^8,9 Clinical practice surveys suggest that the minority of patients with SCAF receive OAC.^10–12

Atrial fibrillation (AF) is responsible for approximately 15% of ischemic strokes and has been proposed as a potential cause in the 25% of strokes that are cryptogenic.^6,13–16 Indeed, the recent 30‐Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) and CRYptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF) studies have documented SCAF in 15–30% of patients with a cryptogenic stroke.^17,18 With the introduction of new, easier to use OAC medications, there is growing enthusiasm to treat SCAF with OAC, as OAC can prevent more than 60% of strokes among patients with clinical AF.^13,19 However, the absolute risk of stroke with SCAF has been shown to be lower than it is for patients with clinical AF, suggesting the need to re‐evaluate the risk–benefit ratio of OAC in this population.^6,7,20 For example, in the ASSERT trial, patients with SCAF and a CHADS2 score of 2 had an annual stroke rate of 1.3% per year⁶ compared with 4.0% per year among patients with a CHADS2 score of 2 and clinical AF.²² Further, the association between stroke and episodes of SCAF as brief as 20 beats,¹⁴ along with the lack of temporal association between SCAF and stroke,^7,15 calls into question the precise mechanism of ischemic stroke in patients with SCAF and hence to potential utility of OAC to prevent stroke.

This international survey was conducted to document physicians’ attitudes regarding the use of OAC to treat patients with SCAF and to evaluate the utility of a randomized trial of OAC in this population.

Methods

National leaders in the field of SCAF from four countries designed a brief survey to evaluate physicians’ attitudes regarding the use of OAC to treat SCAF. They identified a total of 181 cardiologists involved in the care of patients with cardiac devices in their countries. The Population Health Research Institute distributed surveys to these physicians in Canada, Denmark, the Netherlands, and Switzerland. Participating physicians did not receive monetary compensation for their involvement in this study. Respondents were asked to provide details regarding their local pacemaker clinic, their policies regarding the management of SCAF, and to indicate how they would manage a series of hypothetical cases involving individuals with SCAF (Appendix 1) Responses were not anonymous: physician and center identifying data was included for the purposes of data analysis. After initial responses were received, surveys were sent a second time to non‐responding centers via email.

Data analysis

The results of the survey are presented using summary statistics. Quantitative data were compared using a chi‐square test to detect differences in responses between regions, with p = 0.05 considered significant. Data were analyzed using Excel and SPSS Version 21. Unanswered questions were excluded from analyses.

Results

Study demographics

Between September 25, 2012, and November 6, 2012, a total of 91 surveys were completed across the four countries for an overall response rate of 50.3% (Table 1). Of the 91 questionnaires completed, approximately half came from Canadian centers, with the remainder coming from Switzerland, the Netherlands, and Denmark in similar proportions (Table 1). Physicians from Canada and the Netherlands responded at similar rates of 51% and 55%, respectively, while 35% of Swiss physicians and 92% of Danish physicians completed their questionnaire.

Physicians’ patient populations

The responding cardiologists collectively care for 227,280 patients with pacemakers and ICDs (Table 1). On average, each surveyed center follows 2,920 patients (SD = 2,279). However, there is substantial variance between countries: 4,051 patients per center in Canada compared with 577 per center in Switzerland. Within this total cohort of patients with ICDs and pacemakers, approximately 35% of patients have dual or triple‐chamber devices that are capable of detecting SCAF. Approximately 88% of the surveyed physicians’ centers have electronic databases for their pacemaker/ICD patients. Of these, 35% are able to use this information to easily identify patients who have SCAF, and 34% can determine clinical characteristics such as CHADS₂ score in their electronic database.

Current clinical practice at surveyed centers

Clinical management of patients with SCAF varies considerably among centers (Table 1), with fewer than half of the surveyed centers (47%) using a systematic approach to stratify risk and treat patients with SCAF. Only 52% of the centers routinely call physicians to assess most patients with newly documented SCAF, while 32% of the centers consult physicians for assessment in fewer than half of the cases. There is variation in management between regions, with physicians being asked to assess new cases of SCAF in 75% of cases at centers surveyed in Switzerland and Denmark, but in only 45% of cases in the Netherlands and 40% of cases in Canada. In most cases, physicians report that OAC use is infrequent for newly diagnosed cases of SCAF, in the absence of additional clinically documented AF. Only 19% of centers routinely prescribe OAC for patients with SCAF, while approximately one‐third of respondents said that OAC was used infrequently. The remaining of respondents indicated that they did not use OAC to treat SCAF.

Physician perspective on a randomized trial of OAC to treat SCAF

Most surveyed physicians in each of the four countries supported a randomized trial of OAC in patients with SCAF (Table 2) and over 91% indicated their willingness to enroll patients into such a clinical trial. Of willing physicians, 45% indicated that they would still enroll patients with a CHADS₂ score of 2 and no other documentation of clinical AF, even if they had a history of stroke or transient ischemic attack (TIA). Centers in Switzerland (77%) and Denmark (50%) were more willing to enroll these patients in a study than centers in Canada (35%) and the Netherlands (44%). A slightly lower proportion (31%) indicated that they would enroll such patients if the stroke or TIA had occurred in the previous 6 months; however, there was again variation between countries on these issues: Switzerland 77%, Netherlands 33%, Denmark 25%, and Canada 20%.

Many physicians indicated that patients at their centers would not be given OAC, even for very prolonged episodes of SCAF. Confronted with a scenario of a patient with SCAF, a CHADS2 score of 2, but no history of stroke or TIA, 49% of respondents stated they would be willing to enroll a patient into a randomized trial of OAC even if the SCAF was more than 48 h in duration. Support for a clinical trial numerically increased as the length of the SCAF shortened, with 55% of physicians willing to enroll patients with SCAF of between 24 and 48 h in duration; 67% in cases of SCAF between 12 and 24 h in duration and 75% with <6-h SCAF. Some variance was suggested between nations in the willingness to enroll patients with SCAF of >48 h: Canada 41%, the Netherlands 67%, Switzerland 85%, and Denmark 42%. However, there was more agreement regarding patients with SCAF of <6 h: Canada 71%, Netherlands 78%, Switzerland 77%, and Denmark 75%.

Discussion

This study highlights the variation in physicians’ opinion regarding the role of OAC in the treatment of patients with SCAF. This heterogeneity is not surprising as it has only been 5 years since the publication of TRENDS and 2 years since the publication of ASSERT, before which time physicians still questioned whether SCAF was even associated with a risk of stroke. At the same time, the introduction of new oral anticoagulants (NOACs) that are easier than warfarin to initiate in most cardiac device clinic settings may also be causing a shift in physicians’ thinking regarding the appropriate time to initiate OAC.²⁰ It is therefore not surprising that many centers have not yet implemented policies for the routine management of SCAF and look to clinical trials and guidelines for direction.^8,9

The results of this survey suggest that most physicians continue to have equipoise regarding the role of OAC in patients with SCAF and would enroll patients into a clinical trial. Although the benefit of OAC in clinical AF has been well established,^19,20 there are no randomized control data regarding their use in SCAF. The only completed trial using OAC in patients with SCAF is the Home Monitoring Guided Anticoagulation on Stroke Risk in Patients with ICD and CRT‐D Devices (IMPACT) trial,^16,21 which randomized patients to home monitoring for SCAF with a structured algorithm for using OAC compared with standard care.¹⁶ IMPACT failed to show a reduction in stroke among monitored patients; however, IMPACT did not specifically compare OAC versus a placebo control for the treatment of SCAF. As a result, the use of OAC was similar in both arms.¹⁶ The ARTESiA trial (NCT01938248) has just started enrolment of 4,000 pacemaker and ICD patients. It will randomize patients with SCAF and a CHA₂DS₂‐VASc score of >3 with at least one episode of SCAF of between 6 min and 24 h duration to either apixaban or aspirin, and promises to shed further light on the role of OAC for the treatment of SCAF.

Limitations

The following analysis reflects the responses of cardiac device physicians to hypothetical scenarios and may not accurately reflect how these same physicians and their colleagues would act in clinical situations. However, the results appear consistent with clinical practice surveys conducted at approximately the same time.^10,11 Also, there was a response rate to this survey of just over a 50%, thus there may have been significant responder bias. Although one may presume that responders might be more inclined to manage SCAF aggressively, the influence of responder bias is unpredictable. Finally, survey respondents were invited from networks of physicians involved in conducting clinical trials in four countries. Thus, their responses may be more biased in favor of conducting clinical trials and may not be reflective of physicians in other countries.

Conclusions

There is variation in physicians’ attitudes towards the role of OAC in the management of pacemaker and ICD patients with SCAF. Most indicate that they would enroll at least some of their patients with SCAF into a randomized trial of OAC.

References

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Appendix 1

Thank you for taking the time to complete this questionnaire. If you have any questions or concerns, please contact Angie Djuric, ASSERT-IV at +905-527-4322 x 40545 or at Angie.Djuric@phri.ca.