Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy

Abstract

Background: Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24- and 6-month dual antiplatelet therapy groups.

Methods and results: Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS-BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS-BLED. Major bleeding and transfusions were higher in the 24- versus 6-month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (Pint=0.05 and Pint=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24-month rather than 6-month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively.

Conclusions: Our analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all-comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long-term dual antiplatelet therapy regimen.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT00611286" title="See in ClinicalTrials.gov">NCT00611286.

Keywords: ACUITY; CRUSADE; HAS‐BLED; bleeding risk score; clopidogrel; duration of dual antiplatelet therapy.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1

Distribution of bleeding risk scores and major bleeding events in the PRODIGY population. The Venn diagram (center) shows the patients included in the high bleeding risk category by each score. The ACUITY score had broader inclusion in the high‐risk category, whereas CRUSADE and HAS‐BLED were more restrictive (bottom right corner). Bleeding risk score distribution is presented for CRUSADE (top left corner), ACUITY (top right corner), and HAS‐BLED (bottom left corner), with the number of patients with major bleeding in the high‐risk category (gray section) and in the low‐ to intermediate‐risk category according to 3 bleeding definitions. ACUITY indicates Acute Catheterization and Urgent Intervention Triage Strategy; BARC, Bleeding Academic Research Consortium; CRUSADE, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; GUSTO, Global Use of Strategies to Open Occluded Arteries; HAS‐BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly; PRODIGY, Prolonging Dual Antiplatelet Treatment After Grading Stent‐Induced Intimal Hyperplasia Study; TIMI, Thrombolysis in Myocardial Infarction.

Figure 2

Calibration plots comparing the expected and observed probabilities of major bleeding. A, CRUSADE score. B, ACUITY score. C, HAS‐BLED score. ACUITY indicates Acute Catheterization and Urgent Intervention Triage Strategy; CRUSADE, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; HAS‐BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly.

Figure 3

Reclassification tables. The 3 bleeding risk scores are compared using each score as reference for the others: The first score mentioned is the score to be tested, the second is considered the reference. The percentage of patients correctly reclassified by each score is displayed in green, whereas the percentage of patients not correctly reclassified is in red. ACUITY indicates Acute Catheterization and Urgent Intervention Triage Strategy; CRUSADE, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; HAS‐BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly.

Figure 4

Kaplan–Meier curves during follow‐up for hemorrhagic and ischemic events in the high and low to intermediate CRUSADE score categories after 24‐ or 6‐month DAPT. A, Major bleeding. B, Red blood cell transfusion. C, Major adverse cardiovascular events including death for all causes, myocardial infarction, and cerebrovascular accident. CRUSADE indicates Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; DAPT, dual antiplatelet therapy; HAS‐BLED, Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly; HR, hazard ratio.

Figure 5

Hemorrhagic and ischemic outcomes in patients with high and low to intermediate CRUSADE scores. The forest plot shows the absolute risk difference and the P value of the interaction effect for major bleeding, red blood cell transfusion, and MACE after 24‐ versus 6‐month DAPT in the groups of patients with high and low to intermediate CRUSADE scores. CRUSADE indicates Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; DAPT, dual antiplatelet therapy; int, interaction; MACE, major adverse cardiovascular events.

Figure 6

Effects of long‐ and short‐term DAPT on patients with a high CRUSADE score and in the overall population. The number of patients needed to treat to experience major bleeding or red blood cell transfusion after 24‐month DAPT compared with 6‐month treatment is significantly lower in the group of patients with a high CRUSADE score (>40) than in the overall study population. CRUSADE indicates Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines; DAPT, dual antiplatelet therapy.