Performance of Bleeding Risk-Prediction Scores in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention Tuomas Kiviniemi, MD, PhDa,*, Marja Puurunen, MD, PhDb, Axel Schlitt, MD, PhDc, Andrea Rubboli, MDd, Pasi Karjalainen, MD, PhDe, Saila Vikman, MD, PhDf, Matti Niemelä, MD, PhDg, Heli Lahtela, MDa, Gregory Y.H. Lip, MDh, and K.E. Juhani Airaksinen, MD, PhDa The hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, and drugs/alcohol (HAS-BLED); anticoagulation and risk factors in atrial fibrillation (ATRIA); modified Outpatient Bleeding Risk Index (mOBRI); and reduction of atherothrombosis for continued health (REACH) schemes are validated bleeding risk-prediction tools, but their predictive performance in patients with AF receiving multiple antithrombotic drugs after percutaneous coronary intervention (PCI) is unknown. We sought to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation (AF) undergoing PCI. Management of patients with AF undergoing coronary artery stenting is a multicenter European prospective registry enrolling patients with AF undergoing PCI. We calculated HAS-BLED, ATRIA, mOBRI, and REACH bleeding risk-prediction scores and assessed the rate of bleeding complications as defined by Bleeding Academic Research Consortium at 12 months follow-up in 929 consecutive patients undergoing PCI. Increasing age, femoral access site, and previous peptic ulcer were independent determinants of bleeding. Low bleeding risk scores as determined by HAS-BLED 0 to 2, ATRIA 0 to 3, mOBRI 0, and REACH 0 to 10 were detected in 23.7%, 73.0%, 7.8%, and 5.7% of patients of the cohort, respectively. No significant differences were detected in the rates of any bleeding or major bleeding events for low versus intermediate/high scores with each risk-prediction tool. In conclusion, the performance of ATRIA, HAS-BLED, mOBRI, and REACH scores in predicting bleeding complications in this high-risk patient subset was useless. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;-:-e-) Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are at high risk for bleeding complications and death due to the use of multiple antithrombotic drugs.1e3 The hypertension, abnormal renal/ liver function, stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly, drugs/ a

Heart Center, Turku University Hospital and University of Turku, Turku, Finland; bHemostasis laboratory, Finnish Red Cross Blood Service, Helsinki, Finland; cMedical Faculty, Martin Luther University Halle-Wittenberg and Paracelsus-Harz-Clinic Bad Suderode, Halle-Wittenberg, Germany; dDivision of Cardiology, Laboratory of Interventional Cardiology, Ospedale Maggiore, Bologna, Italy; eHeart Center, Satakunta Central Hospital, Pori, Finland; fHeart Center, Tampere University Hospital, Tampere, Finland; gDepartment of Medicine, Oulu University Hospital, Oulu, Finland; and hUniversity of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom. Manuscript received January 12, 2014; revised manuscript received and accepted March 20, 2014. Dr. Tuomas Kiviniemi and Dr. Marja Puurunen are equally contributed authors. This study was supported by unrestricted grants from NovartisGermany and Sanofi-Aventis-Germany and by grants from the Finnish Foundation for Cardiovascular Research, Helsinki, Finland, and the scholarship from the Finnish Cardiac Society, Finland (T.K.). See page 6 for disclosure information. *Corresponding author: Tel: (þ35) 8 2 313 1005; fax: (þ35) 8 2 313 2030. E-mail address: tuoski@utu.fi (T. Kiviniemi). 0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.03.038

alcohol (HAS-BLED)4; anticoagulation and risk factors in atrial fibrillation (ATRIA)5; modified Outpatient Bleeding Risk Index (mOBRI)6,7; and reduction of atherothrombosis for continued health (REACH)8 schemes are validated bleeding risk-prediction tools, but their predictive performance in this frail patient subset remains unknown. We sought to compare the predictive performance of bleeding risk-estimation tools for bleeding events and mortality in a cohort of patients with AF undergoing PCI. Methods Management of patients with AF undergoing coronary artery stenting is an observational, multicenter, prospective registry including patients with AF who are referred for PCI (Clinicaltrials.gov identifier NCT00596570).2,9 Inclusion criteria were elective or acute PCI and (1) history of AF (paroxysmal, persistent, or permanent) or (2) ongoing AF during the index hospital stay. Because of the observational design, the only exclusion criterion was unwillingness/ inability to participate in the study or to give written informed consent. At each of the 17 centers, patients were treated according to local policies and were followed up for 12 months (phone call or outpatient clinic visit at 3, 6, and 12 months). The accuracy of the events and medications were checked using hospital and outpatient clinic records and mortality registries where appropriate. Patients were included from October 2008 to August 2010. Ethic www.ajconline.org

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The American Journal of Cardiology (www.ajconline.org)

Table 1 Baseline characteristics of patients with atrial fibrillation undergoing percutaneous coronary intervention according to bleeding status at 1 year Variable

Median age (years) Women Body mass index (kg/m2) Periprocedural INR Treatment for hypertension Treatment for hypercholesterolemia Diabetes mellitus Current smoker Previous TIA/stroke Previous myocardial infarction Previous percutaneous coronary intervention Previous coronary bypass Previous hemorrhage Previous peptic ulcer Heart failure Mechanical mitral valve Mechanical aortic valve Previous venous thromboembolism Left ventricular ejection fraction (%) Pattern of AF Permanent Persistent Paroxysmal Indication for PCI Acute STEMI NSTEMI Unstable angina pectoris Stable angina pectoris Drug-eluting stents Femoral sheath Medication at discharge Triple Dual antiplatelet VKA and clopidogrel VKA and aspirin Statin NSAID Proton pump inhibitor

Whole Cohort

Bleeding

p Value

(n ¼ 929)

Yes (n ¼ 168)

No (n ¼ 761)

74.0 [11.0] 276 (29.7%) 27.8 [6.0] 1.9 [1.0] 780 (84%) 618 (66.5%) 337 (36.3%) 93 (10.0%) 153 (16.5%) 237 (25.5%) 160 (17.2%) 135 (14.5%) 38 (4.1%) 44 (4.7%) 186 (20.0%) 8 (0.9%) 14 (1.4%) 30 (3.2%) 50.0 [20.0]

75.0 [9.0] 61 (36.3%) 27.8 [5.9] 1.9 [1.0] 136 (81.0%) 110 (65.5%) 59 (35.1%) 16 (9.5%) 26 (15.5%) 45 (26.8%) 31 (18.5%) 23 (13.7%) 9 (5.4%) 13 (7.7%) 41 (24.4%) 3 (1.8%) 4 (2.4%) 9 (5.4%) 50.0 [20.0]

74.0 [11.0] 215 (28.3%) 26.9 [5.4] 1.9 [1.0] 644 (84.6%) 508 (66.8%) 278 (36.5%) 77 (10.1%) 127 (16.7%) 192 (25.2%) 129 (17.0%) 112 (14.7%) 29 (3.8%) 31 (4.1%) 145 (19.1%) 5 (0.7%) 10 (1.3%) 21 (2.8%) 50.0 [20.0]

0.04 0.04 0.07 0.82 0.25 0.79 0.79 0.88 0.82 0.70 0.65 0.81 0.39 0.07 0.14 0.16 0.30 0.09 0.89

460 (49.5%) 108 (11.6%) 354 (38.1%)

87 (51.8%) 22 (13.1%) 57 (38.1%)

373 (49.0%) 86 (11.3%) 297 (39.0%)

0.55 0.51 0.25

126 237 166 399 227 663

(13.6%) (25.5%) (17.9%) (42.9%) (25.0%) (71.4%)

33 45 35 55 35 137

(19.6%) (26.8%) (20.8%) (32.7%) (21.2%) (81.5%)

93 192 131 344 192 526

(12.2%) (25.2%) (17.2%) (45.2%) (25.8%) (69.1%)

0.02 0.70 0.27 0.003 0.23 0.001

679 162 73 15 795 10 335

(73.1%) (17.4%) (7.9%) (1.6%) (85.6%) (1.1%) (36.1%)

119 33 12 4 143 4 68

(70.8%) (19.6%) (7.1%) (2.4%) (85.1%) (2.4%) (40.5%)

560 129 61 11 652 6 267

(73.6%) (17.0%) (8.0%) (1.4%) (85.7%) (0.8%) (35.1%)

0.50 0.43 0.87 0.33 0.85 0.16 0.32

Data are presented as mean  SD, median [IQR] and count (%). IQR ¼ interquartile range; NSAID ¼ nonsteroidal anti-inflammatory drugs; NSTEMI ¼ noneST-elevation myocardial infarction; STEMI ¼ ST-elevation myocardial infarction; TIA ¼ transient ischemic attack; VKA ¼ vitamin K-antagonist.

committees of participating centers approved the study protocol, and written informed consent was obtained from every patient. The study complied with the Declaration of Helsinki. Coronary angiography and PCI were performed using either radial or femoral approach for arterial access, and hemostasis was obtained according to the local practice. Lesions were treated according to the contemporary interventional techniques. Low-molecular weight heparin (LMWH), unfractionated heparin, bivalirudin, and glycoprotein IIb/IIIa inhibitors were administered at the operator’s discretion. Moreover, the choice of the combination of antithrombotic treatment after the procedure was at the treating physician’s discretion. HAS-BLED, ATRIA, mOBRI, and REACH bleeding risk scores were calculated for each patient based on the definitions used in their validation cohorts.4e6,8 In HAS-

BLED score, each risk factor (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, and drugs/alcohol) is calculated as 1 point, and patients with scores 3 are considered to be at intermediate/high bleeding risk. In the HAS-BLED score, labile INR and impaired liver function could not be assessed, and these were therefore omitted so that a maximum of 7 points was used for a “modified HASBLED” analysis. For the ATRIA score, anemia (hemoglobin