Alert-Based Computerized Decision Support to Increase Anticoagulation

Prescription Prevents Stroke and Myocardial Infarction in High-Risk

Hospitalized Patients with Atrial Fibrillation: A Randomized, Controlled Trial (AF-ALERT)

Gregory Piazza, MD, MSDivision of Cardiovascular Medicine

Brigham and Women’s HospitalNovember 10, 2018

Investigator-Initiated Trial funded by Daiichi-Sankyo, Inc.

Failure to Prescribe Anticoagulation for Stroke Prevention in AF

• Despite a multitude of evidence-based clinical practice guidelines and five effective oral anticoagulants for stroke prevention, at least 30% of AF patients remain unprotected.

• In our prior observational analysis of 5,000 hospitalized patients with AF, antithrombotic therapy was omitted in nearly 40% of those at risk.

• Failure to prescribe antithrombotic therapy in these high-risk patients resulted in a 36% increase in major adverse events, including stroke and myocardial infarction (MI).

• This low rate of adherence to guideline recommendations for stroke prevention in AF highlights a critical gap in implementation of best clinical practice among providers.

• Alert-based computerized decision support (CDS) strategies have been successfully implemented to improve underutilization of venous thromboembolism (VTE) prophylaxis in high-risk hospitalized patients.

Piazza G, et al. TH Open. 2018;2:e33-e38.Piazza G, Goldhaber SZ. Circulation. 2009;120:1133-1137.

Objective and Hypothesis

•Objective: To determine the impact of alert-based CDS on prescription of anticoagulation, we conducted a randomized controlled trial in high-risk hospitalized patients with AF who were not already prescribed anticoagulation.

•Hypothesis: Alert-based CDS will increase prescription of anticoagulation in high-risk hospitalized patients with AF who were not being prescribed anticoagulation.

Primary and Secondary Endpoints

•Primary Efficacy Endpoint: the rate of anticoagulation prescription during hospitalization, at discharge, and at 90 days

•Secondary Efficacy Endpoint: the occurrence of a composite of major adverse cardiovascular events, defined as stroke/TIA, systemic embolism, myocardial infarction (MI), and all-cause mortality at 90 days from enrollment

•Primary Safety Endpoint: the occurrence of major bleeding or clinically relevant non-major bleeding (defined by the International Society on Thrombosis and Haemostasis [ISTH] bleeding classification system) at 90 days from enrollment

Schulman S, Kearon C. J Thromb Haemost. 2005;3:692-694

Patient SelectionInclusion Criteria:

1. Hospitalized patient with AF 2. CHA2DS2-VASc ≥1 3. No active order for

anticoagulation

• Based on prior trial data, we estimated that CDS would increase prescription of anticoagulation by 80% and that we would require 400 patients (80% power; two-sided α = 0.05).

Alert-Based CDS Intervention

• Eligible patients were randomly allocated to the alert and control groups by the CDS program, according to Attending Physician identification number.

• By allocating according to Attending Physician, we minimized a cluster-effect around specific clinicians, while also maintaining unpredictable group assignment.

• The providers responsible for writing admission orders for patients assigned to the alert group received an on-screen alert (EPIC BPA).

Baseline Clinical CharacteristicsCharacteristic Alert

N = 248ControlN = 210

p-value

Mean age ± SD, years 73.5 ± 11.8 73.3 ± 13 0.95Male, n (%) 136 (54.8) 117 (55.7) 0.85Race/Ethnicity, n (%)

WhiteHispanic/LatinoBlack or African-American Other

201 (81.1)16 (6.5)25 (10.1)22 (8.9)

175 (83.3)11 (5.2)16 (7.6)19 (9.0)

0.530.580.360.95

Mean BMI ± SD, kg/m2 28.3 ± 7.3 27.4 ± 7.1 0.13Cardiomyopathy, n (%)

Mean ejection fraction ± SD, (%)46 (18.6)38 ± 15

33 (15.7)38.9 ± 14.9

0.420.88

Cancer (active or within past 5 years), n (%) 136 (54.8) 117 (55.7) 0.35Coronary artery disease, n (%) 96 (38.7) 70 (33.3) 0.23Concomitant medications, n (%)

AspirinP2Y12 receptor inhibitor

137 (55.2)18 (7.3)

106 (50.5)8 (3.8)

0.310.11

Median CHA2DS2-VASc score (minimum, maximum), points 4 (1, 9) 4 (1, 8) 0.46Median HAS-BLED score (minimum, maximum), points 3 (0, 7) 3 (0, 7) 0.53

Primary Efficacy Endpoint

Characteristic, n (%) AlertN = 248

ControlN = 210

p-value

Clinical response to alertOpen stroke prevention order setRead AF guidelinesExit and provide rationale

88 (35.4)2 (0.8)

158 (63.7)

- -

Rationale for not prescribing anticoagulation*Bleeding riskFall riskOther

122 (50.0)31 (12.0)95 (38.0)

- -

Anticoagulation prescribed during hospitalization 64 (25.8) 20 (9.5) <0.0001Anticoagulation prescribed at discharge 59 (23.8) 27 (12.9) 0.003Anticoagulation prescribed at 90 days 69 (27.8) 36 (17.1) 0.007Anticoagulation prescribed during hospitalization, at discharge, and at 90 days 48 (19.4) 15 (7.1) <0.001

*More than one reason could have been provided

Secondary Efficacy and Primary Safety EndpointsOutcome, n (%) Alert

N = 248ControlN = 210

p-value

Death, myocardial infarction, stroke, TIA, or systemic embolic event

28 (11.3) 46 (21.9) 0.002

Death 25 (10.1) 31 (14.8) 0.13Myocardial infarction 3 (1.2) 18 (8.6) <0.001Stroke or TIA 0 (0) 4 (1.9) 0.04Stroke, TIA, or systemic embolic event 0 (0) 5 (2.4) 0.02Major or clinically relevant non-major bleed 11 (4.4) 16 (7.6) 0.15TIA, transient ischemic attack

Freedom from Secondary Composite EndpointsFreedom from major adverse CV events (MACE) at 90 days (death, MI, and Stroke/TIA/systemic embolism)

Freedom from major adverse events at 90 days (death, MI, Stroke/TIA/systemic embolism, and major/clinically relevant non-major bleed)

Alert

ControlAlert

Control

Hazard Ratio, 0.50 (95% CI, 0.31-0.81); p = 0.004 Hazard Ratio, 0.48 (95% CI, 0.31-0.73); p = 0.001

Cumulative Incidences of MI and Stroke/TIA/Systemic Embolism

Cumulative Incidence of MI at 90 daysCumulative Incidence of Stroke/TIA/Systemic Embolism at 90 days

Gray’s test, p = 0.0002

Gray’s test, p = 0.01

Alert

Control

Alert

Control

Discussion

• Alert-based CDS increased prescription of anticoagulation for stroke prevention in AF during hospitalization, at discharge, and at 90 days after randomization in high-risk AF patients.

• Alert-based CDS resulted in a 50% reduction in a secondary composite outcome of death, MI, and stroke/TIA/systemic embolism at 90 days.

• The reduction in major adverse cardiovascular events was attributable to reductions in MI and stroke/TIA at 90 days in patients whose physicians received the alert.

Discussion

• In our study, CDS reduced a secondary outcome of major adverse cardiovascular events beyond what was anticipated from the increase in prescription of anticoagulation.

• We observed a similar phenomenon in a prior randomized controlled trial of alert-based CDS focused on VTE prevention.

• Our study shares similarities with a prior randomized controlled trial of a multifaceted educational intervention that increased prescription of anticoagulation and reduced stroke.

Kucher N, et al. N Engl J Med. 2005;352:969-977Vinereanu D, et al. Lancet. 2017;390:1737-1746

Limitations

• Implementation of alert-based CDS requires an investment in programming and medical informatics infrastructure which may not be available at some medical centers.

• Our patient population may not match the profile of AF patients at other centers.

• The most dramatic finding of our study, reduction of major adverse cardiovascular events, constituted our secondary, not our primary, end point.

Conclusions

• Alert-based CDS nearly tripled prescription of anticoagulation in hospitalized AF patients at increased risk for stroke.

• Alert-based CDS reduced a secondary endpoint of major adverse cardiovascular events, including myocardial infarction and stroke.

• CDS has the potential to be a powerful tool in prevention of cardiovascular events in patients with AF.

THANK YOU!