Methods

The ACUITY trial design and primary results have been previously described in detail. Briefly, ACUITY was a multicenter, prospective, randomized trial of 13,819 patients with moderate- and high-risk NSTEACS who were treated with an early invasive strategy. Major inclusion criteria were age ≥18 years with symptoms of unstable angina lasting ≥10 minutes duration within 24 hours of randomization and ≥1 of the following: new ST-segment depression or transient elevation of at least 1 mm, cardiac biomarker elevations, known coronary artery disease, or all 4 other variables as part of the thrombolysis in myocardial infarction risk score for unstable angina. Exclusion criteria included acute ST-segment elevation myocardial infarction or shock; bleeding diathesis or recent major bleeding episode; thrombocytopenia; estimated glomerular filtration rate by the Cockcroft-Gault equation of <30 ml/min/1.73 m ² ; recent antithrombotic or thrombolytic agent administration; and allergy to study drugs or iodinated contrast medium not amenable to pretreatment.

Before coronary angiography, patients were randomly assigned to heparin (unfractionated or low molecular weight) plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy. Angiography was performed within 72 hours of randomization, and depending on coronary anatomy, patients were triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical therapy. In patients who underwent PCI, stent choice (bare metal or drug eluting) was per operator discretion. Aspirin and clopidogrel were recommended for at least 1 year. An independent clinical events committee, blinded to treatment assignment, adjudicated all major adverse events.

Our primary objective was to assess the relation between SS and risk of developing AKI within 48 hours after PCI for NSTEACS. We included only patients in whom quantitative coronary angiography was performed by experienced core laboratory technicians, blinded to randomization and clinical outcomes (Cardiovascular Research Foundation, New York, New York), as part of the formal ACUITY angiographic substudy. Because the SS had only been validated for native coronary arteries at the time of our angiographic analysis, patients with previous CABG were excluded.

Three experienced interventional cardiologists (P.G., T.P., and A.C.), who were also blinded to randomization and clinical outcomes, assessed the SS for each angiogram. Lesions causing ≥50% reduction in luminal diameter in vessels with a minimal diameter of 1.5 mm were scored using the SS algorithm as described elsewhere. The Fleiss kappa statistic (tertile partitioning), determined by each of the 3 readers independently reading 50 films, was 0.57. This value signifies a moderate level of interobserver agreement comparable with what was achieved in the SYNTAX trial. Additionally, in an effort to determine the association between the completeness of revascularization, the SS, and rates of postprocedural AKI, the previously described residual SS (assessed after PCI) was determined for each group.

Rates of AKI were assessed using 2 definitions, based on severity of postprocedural renal dysfunction. First, we applied the most widely adopted definition: a rise in serum creatinine from baseline by ≥0.5 mg/dl or ≥25% within 48 hours post-PCI. Additionally, severe AKI was defined as a serum creatinine increase of ≥1 mg/dl or ≥50% within 48 hours after PCI. We also determined rates of death (cardiac and noncardiac), myocardial infarction, ischemia-driven target vessel revascularization (TVR), non-CABG major and minor bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE), for which definitions have been previously reported. MACE was defined as any death, myocardial infarction, or unplanned ischemia-driven TVR. NACE was defined as any MACE or non-CABG major bleeding. Non-CABG major bleeding was defined as intracranial or intraocular bleeding, access site hemorrhage requiring intervention, hematoma ≥5 cm in diameter, reduction in hemoglobin levels ≥4 g/dl without an overt bleeding source or ≥3 g/dl with an overt source, reoperation for bleeding, or any blood product transfusion.

We stratified patients by SS based on true tertile cutoffs from the ACUITY trial population (<7, 7 to 12, and >12). We also divided patients by tertile cutoffs from the original SYNTAX trial (<23, 23 to 32, and >32). Score ranges will be referred to as SS _<7 , SS _{7 to 12} , and SS _>12 and SS _<23 , SS _{23 to 32} , and SS _>32 , respectively. To assess how the purely angiographic SS compared with clinical scores for AKI, the Mehran risk score was determined using the following variables: age >75 years, anemia, chronic kidney disease, diabetes, intra-aortic balloon pump, and contrast volume. Continuous data are presented as mean ± SD and were compared using the Student t test or analysis of variance, as appropriate. Binary variables (including in-hospital outcomes) are presented as n (%) and were compared between groups with the chi-square test. Thirty-day and 1-year event rates were estimated using Kaplan-Meier methodology and compared using the log-rank test. Multivariable regression analysis using logistic regression models for in-hospital time points was performed to assess the association between SS and AKI with variable entry/stay criteria of 0.1/0.1. Variables for the multivariable models were those selected known from previous studies to be related to AKI and others with statistical significance in univariate analysis, including SS (in 10-point increments), age (in 10-year increments), hypertension, hyperlipidemia, diabetes, current smoking status, baseline anemia, baseline renal insufficiency (estimated glomerular filtration rate <60 ml/min/1.73 m ² ), previous myocardial infarction, previous PCI, cardiac biomarker elevation, baseline white blood cell count, baseline platelet count, baseline angiotensin-converting enzyme inhibitor usage, contrast volume, intra-aortic balloon pump use, anticoagulant choice (heparin vs bivalirudin), and stent choice (drug eluting vs bare metal). p Values <0.05 were considered to be statistically significant. Statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, North Carolina).

Results

The angiographic substudy of ACUITY included 6,921 patients, of whom 3,826 received PCI. After excluding patients with a history of CABG (n = 862), those in whom the SS could not be calculated due to technical reasons (n = 337), and those with missing serial creatinine measures (n = 359), the analysis cohort consisted of 2,268 patients. The SS ranged from 0 to 59.5, with a mean ± SD of 11.6 ± 8.4 and median and interquartile range of 9 (5, 16). The Mehran risk scores ranged from 0 to 29 with mean of 4.8 ± 3.5 and a median of 4 (2, 7).

AKI within 48 hours of intervention developed in 226 patients (10%); 72 patients (3.2%) had renal injury that was categorized as severe AKI. Table 1 lists baseline patient clinical characteristics in patients who did and did not develop AKI. Patients who developed renal dysfunction were more likely to be older, women, diabetics, and have hypertension. These patients had lower baseline hemoglobin counts and were more likely to have cardiac biomarker elevation on presentation. The Mehran risk score was significantly higher in the group who developed AKI.

Patients who developed AKI had significantly higher baseline SS compared with those with preserved renal function postprocedurally, and the angiographic components of the SS as well as treatment variables are listed in Table 2 . The AKI group was more likely to receive bare-metal stents; however, there were no differences in antithrombotic regimens or intraprocedural glycoprotein IIb/IIIa inhibitor usage. Table 3 lists baseline characteristics and treatment strategies stratified by the ACUITY SS tertiles. Procedural duration and contrast volume increased significantly by SS tertile.

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