Regular Bleeding Risk Assessment Associated with Reduction in Bleeding Outcomes: The mAFA-II Randomized Trial

doi:10.1016/j.amjmed.2020.03.019

The American Journal of Medicine

Volume 133, Issue 10, October 2020, Pages 1195-1202.e2

https://doi.org/10.1016/j.amjmed.2020.03.019 Get rights and content

Abstract

Background

The mobile atrial fibrillation application (mAFA-II) randomized trial reported that a holistic management strategy supported by mobile health reduced atrial fibrillation-related adverse outcomes. The present study aimed to assess whether regular reassessment of bleeding risk using the Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol (HAS-BLED) score would improve bleeding outcomes and oral anticoagulant (OAC) uptake.

Methods

Bleeding risk (HAS-BLED score) was monitored prospectively using mAFA, and calculated as 30 days, days 31-60, days 61-180, and days 181-365. Clinical events and OAC changes in relation to the dynamic monitoring were analyzed.

Results

We studied 1793 patients with atrial fibrillation (mean, standard deviation, age 64 years, 24 years, 32.5% female).

Comparing baseline and 12 months, the proportion of atrial fibrillation patients with HAS-BLED ≥3 decreased (11.8% vs 8.5%, P = .008), with changes in use of concomitant nonsteroidal antiinflammatory drugs/antiplatelets, renal dysfunction, and labile international normalized ratio contributing to the decreased proportions of patients with HAS-BLED ≥3 (P < .05). Among 1077 (60%) patients who had 4 bleeding risk assessments, incident bleeding events decreased significantly from days 1-30 to days 181-365 (1.2% to 0.2%, respectively, P < .001). Total OAC usage increased from 63.4% to 70.2% (P_trend < .001). Compared with atrial fibrillation patients receiving usual care (n = 1136), bleeding events were significantly lower in atrial fibrillation patients with dynamic monitoring of their bleeding risk (mAFA vs usual care, 2.1%, 4.3%, P = .004). OAC use decreased significantly by 25% among AF patients receiving usual care, when comparing baseline to 12 months (P < .001).

Conclusion

Dynamic risk monitoring using the HAS-BLED score, together with holistic App-based management using mAFA-II reduced bleeding events, addressed modifiable bleeding risks, and increased uptake of OACs.

Introduction

Oral anticoagulants (OAC) are highly effective for the prevention of stroke in patients with atrial fibrillation.¹^,² However, bleeding events are a detrimental side effect of OAC use, even despite the reduced risk of intracranial hemorrhage with the use of nonvitamin K antagonist oral anticoagulants (NOACs), with major bleeding rates at 2% to 4% and any bleeding of 11%-18% per year.³ Some of these bleeding events are nonclinically relevant bleeding, and overall, there is a positive net clinical benefit for using OACs for stroke prevention for the majority of atrial fibrillation patients.⁴ Nevertheless, the perceived fear of bleeding, among physicians and patients, results in lower OAC prescription and uptake and poor adherence with guidelines and dosing recommendations in patients with atrial fibrillation, especially in Asian populations.

At the practical level, the assessment of modifiable bleeding risk factors, anticoagulant adherence, and checks for thromboembolic and bleeding events have been proposed during follow-up of atrial fibrillation patients taking OAC.⁵ There are several risk factors for bleeding, and the more common and validated factors have been used to derive risk-stratification scores to aid clinical decision-making.⁶^,⁷ In various systematic reviews and evidence appraisals, the Hypertension, Abnormal renal and liver function, history of Stroke or thromboembolism, history of Bleeding or bleeding diathesis (eg, severe anemia), Labile international normalized ratio (INR), Elderly (age >65 years), use of aspirin or nonsteroidal antiinflammatory Drugs, and alcohol abuse, the HAS-BLED score has been found to have the best evidence for predicting bleeding risk, compared with other clinical risk scores for bleeding.⁸ Indeed, these reviews and evidence appraisals are complemented by various other studies, including those from Asian cohorts,⁹^,¹⁰ that have shown that formal bleeding risk assessment tools are superior to a strategy that uses only modifiable bleeding risk factors for assessment of bleeding risk.⁹^,11, 12, 13 The HAS-BLED score was introduced to draw attention to modifiable bleeding risk factors and to identify patients with atrial fibrillation at high risk of bleeding on OAC for early review and closer follow-up.¹⁴

With greater awareness of bleeding (and stroke) risk over time, management of OAC therapy can be tailored, modifiable bleeding risks managed, and follow-up visits individually scheduled as part of an integrated care management patient pathway. This integrated approach would require consideration of the patients' preferences,¹⁵ physicians' decision-making support,¹⁶ and good physician–patient communication. The increasing use of mobile health technology can provide an easy-to-use tool, thereby streamlining decision support, improved patient knowledge, and drug adherence, as well as facilitating the implementation of educational programs for both patients and physicians/health care professionals.17, 18, 19

In the mobile health to improve optimization of integrated care in patients with atrial fibrillation (mobile Atrial Fibrillation Application [mAFA-II]) prospective randomized trial, we reported that a holistic management strategy using App-based mobile health technology support reduced atrial fibrillation-related adverse outcomes, compared with usual care.²⁰ The objective of this ancillary analysis from the mAFA-II clinical trial was to assess whether regular reassessment of bleeding risk using the HAS-BLED score, over a 12-month period, would improve bleeding outcomes and OAC uptake, with the support of mobile health technology.

Section snippets

Methods

The design and rationale of the mAFA-II trial has been previously described.¹⁹ In brief, the mAFA-II trial was a 2-arm, prospective, cluster-randomized controlled clinical trial that enrolled patients with atrial fibrillation, within randomized participating centers to either the mAFA intervention with integrated care, or to usual care. The study was registered on World Health Organization International Clinical Trials Registry Platform chictr.org.cn, with registration number

Results

There were 1793 patients with atrial fibrillation (mean [SD] age 64 [24] years, female 583 (32.5%); 919 (51.3%) with paroxysmal atrial fibrillation), who used the “"?>Avoid stroke with Anticoagulants”"?> part of the mAFA. Common comorbidities in these patients were hypertension, coronary artery disease, and obstructive sleep apnea syndrome (Table 1).

Comparing baseline and 12-month HAS-BLED scores, the proportion of atrial fibrillation patients with HAS-BLED ≥3 decreased significantly (11.8%,

Discussion

The main findings of the present ancillary study to the mAFA trial program were: 1) the bleeding risks of atrial fibrillation patients are dynamic, and with regular re-assessments using the mAFA intervention and proactive management of modifiable bleeding risk factors, the proportion of patients with high-risk HAS-BLED scores decreased significantly over time, especially after 6 months; 2) concomitant drugs (NSAIDs/antiplatelets), renal dysfunction, and labile INR were the common modifiable

Conclusions

In this prospective clinical trial cohort, dynamic risk monitoring and reassessment of bleeding risk using the HAS-BLED score, together with holistic App-based management using mAFA-II, was associated with a reduction in bleeding events, addressing modifiable bleeding risks and increased uptake of OACs.

Acknowledgments

The authors would like to thank Wang Xiaoxian, who lead the information technology team, for the design and extraction of formatting data from the mAFA platform, and Li Weixin, who lead the Telecare team, for follow-up of the patients.

References (30)

GYH Lip et al.
Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report
Chest
(2018)
CT Ruff et al.
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials
Lancet
(2014)
H Zulkifly et al.
Bleeding risk scores in atrial fibrillation and venous thromboembolism
Am J Cardiol
(2017)
G Chang et al.
Accuracy of HAS-BLED and other bleeding risk assessment tools in predicting major bleeding events in atrial fibrillation: a network meta-analysis
J Thromb Haemost
(2020)
Y Guo et al.
Comparing bleeding risk assessment focused on modifiable risk factors only versus validated bleeding risk scores in atrial fibrillation
Am J Med
(2018)
TF Chao et al.
Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study
Int J Cardiol
(2018)
GY Lip et al.
Bleeding risk assessment in atrial fibrillation: observations on the use and misuse of bleeding risk scores
J Thromb Haemost
(2016)
Y Guo et al.
Mobile Health to improve optimization of integrated care in patients with atrial fibrillation: mAFA-II trial
J Am Coll Cardiol
(2020)
TY Chang et al.
Importance of Risk Reassessment in Patients With Atrial Fibrillation in Guidelines: Assessing Risk as a Dynamic Process
Can J Cardiol
(2019)
S Miyamoto et al.
Clinical risk factors of thromboembolic and major bleeding events for patients with atrial fibrillation treated with rivaroxaban in Japan
J Stroke Cerebrovasc Dis
(2020)

G Lip et al.

Stroke prevention in atrial fibrillation: Past, present and future. Comparing the guidelines and practical decision-making

Thromb Haemost

(2017)

L Friberg et al.

Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study

Circulation

(2012)

J Steffel et al.

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Eur Heart J

(2018)

ED Borre et al.

Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review

Thromb Haemost

(2018)

YT Guo et al.

Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: the Beijing PLA Hospital Atrial Fibrillation Project

Sci Rep

(2016)

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Citation Excerpt :
Amongst patients who had a change in their bleeding risk profile, there was a 3.5 fold higher risk of major bleeding in the first 3 months [33]. In the mAFA-II trial, use of the HAS-BLED score (together with structured care in an integrated or holistic approach) was associated with lower major bleeding events, mitigation of modifiable bleeding risk factors, and an increase in OAC uptake at 12 months, when compared to ‘usual care’ [45]. For decision making, the first step is to identify low-risk patients who do not need antithrombotic therapy.
Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder associated with an increased risk of stroke and systemic embolic events. The prevention of stroke using oral anticoagulants has been a pivotal component of AF management. The purpose of this review is to summarize recent advances in the treatment and prevention of stroke in AF over the last 5 years. We performed a comprehensive structured literature search using MEDLINE for publications from 11^th March 2015 through to 31^st December 2020. We focused mainly on primarily published research articles and systematic reviews including updates in different international guidelines. We found that improved awareness and detection of AF and use of clinical risk stratification are central to the identification of patients at risk of stroke who would benefit from oral anticoagulation. The recommendation of non-vitamin K antagonist oral anticoagulants over warfarin in both efficacy and safety perspective is represented in all international guidelines. Beyond stroke prevention, there is a move to more holistic or integrated care management of AF, which has been shown to improve outcomes. We conclude that stroke prevention remains a dominant part of the management of patients with AF. Not all stroke risk factors carry equal weight, and many require additional scrutiny (e.g. severity of CAD, type of diabetes, duration of hypertension). The utilization of clinical risk scores to help decision-making should take into account that these scores are mere simplification tools to aid decision-making and the additional clinical benefit with more complex risk scores and addition of biomarkers is limited. Also, stroke and bleeding risks are dynamic and require regular review. Instead of arbitrarily categorizing patients into (artificial) low, moderate, and high stroke risk strata, anticoagulation should be offered to all patients with AF unless they are low risk with no risk factors for stroke. Stroke prevention is also part of the proactive, integrated care approach to holistic management of patients with AF, which can be simplified in the ABC (Atrial fibrillation Better Care) pathway: ‘A’ Avoid stroke/Anticoagulation; ‘B’ Better symptom management emphasising patient-centred symptom directed decisions on rate or rhythm control strategies; and ‘C’ refers to Cardiovascular risk and comorbidity optimization, including lifestyle changes and attention to patient values and preferences, as well as the psychological morbidity associated with AF.

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: Funding: This research project was funded by the National Natural Science Foundation of China (H2501) and was funded by the Health and Family Planning Commission of Heilongjiang Province, China (2017-036), and partly supported by the National Institute for Health Research Global Health Research Group on Atrial Fibrillation managed by the University of Birmingham, UK. This study was an investigator-initiated project, with limited funding by independent research and educational grants. Funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

: Conflict of Interest: GYHL: Consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. DAL has received investigator-initiated educational grants from Bristol-Myers Squibb (BMS) and Boehringer Ingelheim; has been a speaker for Boehringer Ingelheim, Bayer, and BMS/Pfizer; and has consulted for BMS, Bayer, Boehringer Ingelheim, and Daiichi-Sankyo. Other authors: None declared.

: Authorship: All authors had access to the data and contributed to drafting the article or revising it critically for important intellectual content.

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Clinical Research StudyRegular Bleeding Risk Assessment Associated with Reduction in Bleeding Outcomes: The mAFA-II Randomized Trial

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Acknowledgments

Chest

Lancet

Am J Cardiol

J Thromb Haemost

Am J Med

Int J Cardiol

J Thromb Haemost

J Am Coll Cardiol

Can J Cardiol

J Stroke Cerebrovasc Dis

Stroke prevention in atrial fibrillation: Past, present and future. Comparing the guidelines and practical decision-making

Thromb Haemost

Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study

Circulation

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Eur Heart J

Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review

Thromb Haemost

Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: the Beijing PLA Hospital Atrial Fibrillation Project

Sci Rep

Clinical Research Study
Regular Bleeding Risk Assessment Associated with Reduction in Bleeding Outcomes: The mAFA-II Randomized Trial