Author + information
- Received February 12, 2018
- Revision received April 2, 2018
- Accepted April 5, 2018
- Published online August 20, 2018.
- Roxana Mehran, MDa,∗ (, )
- Michela Faggioni, MDa,
- Jaya Chandrasekhar, MBBS, MSa,
- Dominick J. Angiolillo, MD, PhDb,
- Barry Bertolet, MDc,
- Robert Lee Jobe, MDd,
- Bassam Al-Joundi, MDe,
- Somjot Brar, MDf,
- George Dangas, MD, PhDa,
- Wayne Batchelor, MD, MHSg,
- Anand Prasad, MDh,
- Hitinder S. Gurm, MDi,
- James Tumlin, MDj and
- Gregg W. Stone, MDk
- aIcahn School of Medicine at Mount Sinai, New York, New York
- bUniversity of Florida College of Medicine–Jacksonville, Jacksonville, Florida
- cNorth Mississippi Medical Center, Tupelo, Mississippi
- dNorth Carolina Heart & Vascular, Raleigh, North Carolina
- eGateway Cardiology, Saint Louis, Montana
- fKaiser Permanente Los Angeles Medical Center, Los Angeles, California
- gTallahassee Memorial Hospital, Heart and Vascular Center, Tallahassee, Florida
- hDivision of Cardiology, Department of Medicine, The University of Texas Health Science Center San Antonio, San Antonio, Texas
- iDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan
- jDepartment of Internal Medicine, Division of Nephrology, University of Tennessee College of Medicine in Chattanooga, Southeast Renal Research Institute, Chattanooga, Tennessee
- kColumbia University Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York
- ↵∗Address for correspondence:
Dr. Roxana Mehran, Mount Sinai Hospital, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
Objectives The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.
Background CI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection.
Methods The AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m2 or estimated glomerular filtration rate 30 to 60 ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (n = 292) or hydration only (n = 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2) the incidence of CI-AKI, defined as a ≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure.
Results Patient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; p = 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; p = 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; p = 0.01) when ≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; p = 0.70) between the study groups.
Conclusions Use of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299)
Contrast-induced acute kidney injury (CI-AKI) is the most common cause of iatrogenic renal failure in patients undergoing percutaneous coronary intervention (PCI) (1). The prevalence of CI-AKI in the general population after PCI is approximately 10% to 12% but can reach 20% to 30% in patients with prior chronic kidney disease (CKD) (2,3), with the rate depending in part on the definition used for CI-AKI (4,5). Treatment of CI-AKI is limited to supportive measures and usually results in prolonged hospitalization and higher health care costs (6). In addition, development of CI-AKI is associated with increased short- and long-term morbidity and mortality (7). Models have been developed to stratify the risk for CI-AKI on the basis of baseline and procedural characteristics such as prior CKD, diabetes, age, hypotensive state, heart failure, anemia, and contrast media volume (CMV) used (8). In patients at moderate or high risk for CI-AKI, every effort should be made to remove modifiable risk factors and implement preventive strategies to avoid renal damage.
Prophylactic measures for CI-AKI include periprocedural hydration, use of low osmolar contrast medium, and reducing the CMV used during the procedure (9,10). The CMV used is an independent predictor of CI-AKI, and there is no specific threshold of contrast medium exposure below which the risk is eliminated (8). The AVERT system (Osprey Medical, Minnetonka, Minnesota) consists of a contrast modulator for manual contrast medium injections that adapts the coronary injection pressure profile to minimize CMV. The AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial tested the efficacy of the AVERT system to reduce the CMV used during coronary angiographic procedures without impairing image quality and to prevent CI-AKI in patients at risk for CI-AKI.
The AVERT trial was a prospective, randomized, parallel group, multicenter clinical study that compared periprocedural hydration alone with periprocedural hydration plus procedural use of the AVERT system in patients at risk for CI-AKI undergoing coronary angiography with or without PCI (NCT01976299). The trial was designed by the principal investigator and executive committee and was sponsored by Osprey Medical. The study was reviewed and approved by Institutional Review Boards at all participating sites, and all patients provided informed written consent.
Consecutive patients ≥18 years of age who were undergoing coronary angiography with or without PCI and who were at increased risk for CI-AKI were considered for enrollment. Patients were enrolled with non–ST-segment elevation myocardial infarction, unstable angina, stable angina with positive stress test results, and silent ischemia. Patients were considered at risk for CI-AKI if baseline estimated glomerular filtration rate (eGFR) was between 20 and 30 ml/min (stage IV CKD) or if eGFR was between 30 and 60 ml/min (stage III) and 2 or more of the following CI-AKI risk predictors were present: New York Heart Association functional class III or IV criteria for heart failure, insulin-treated diabetes or type 2 diabetes on oral medications, albuminuria (≥2+ on urine dipstick), anemia (hemoglobin <12 g/dl in women and <13 g/dl in men), hypertension, and age ≥75 years. Principal exclusion criteria included acute renal failure or unstable renal function as evidenced by a change in serum creatinine (SCr) of >0.5 mg/dl or >25% within 7 days; contrast medium exposure within 7 days with change in SCr ≥0.1 mg/dl on 2 SCr measures ≥24 h apart; inability to receive periprocedural hydration; dialysis; use of nephrotoxic agents (aminoglycoside antibiotics, sulfonamides, amphotericin B, or pentamidine); need for >10 ml of iodinated contrast medium in any location other than the coronary arteries (e.g., ventriculography, aortography, renal angiography) during the procedure or within a period of 30 days after the procedure, prior organ transplantation; use of cisplatin or an active chemotherapy agent; hemodynamic instability or necessity for hemodynamic support including intravenous inotropes, vasopressors, or any type of ventricular assist devices; or acute ST-segment elevation myocardial infarction within 72 h.
Study protocol and randomization
Patients were randomly assigned in a 1:1 ratio to periprocedural hydration alone (control arm) or periprocedural hydration plus intraprocedural use of the AVERT system (AVERT arm) (Figure 1), stratified by investigational center and diabetes status. The pre-procedural hydration protocol included a minimum of 2 h of isotonic saline or sodium bicarbonate at 1.0 to 1.5 ml/kg/h. Post-procedural hydration after PCI was 1.0 to 1.5 ml/kg/h for at least 6 h. In subjects undergoing coronary angiography only, post-procedural hydration was per the institutional standard of care. For patients with medical conditions sensitive to hydration volume (e.g., heart failure), a lower hydration rate of 1.0 ml/kg/h was recommended, and the timing and total volume of hydration were adjusted as clinically indicated. Use of N-acetylcysteine was permitted as an additional treatment at the discretion of the investigator. Patients were blinded to the randomized assignment. A blood sample was collected to measure SCr and estimate glomerular filtration rate before the pre-procedural hydration. Contrast medium options included iso-osmolar iodixanol (270 or 320 mg iodine/ml), low osmolar iohexol (300 or 350 mg iodine/ml), or low osmolar iopamidol (370 mg iodine/ml). The type and concentration of contrast medium used were at the discretion of the investigator.
CMV used was determined through standardized accounting steps for both treatment and control groups. Each procedure started with a new bottle of contrast, establishing a contrast start volume. Contrast used on the table for priming, wasting, or other related activities was monitored in real time during the procedure. At procedure completion, all tubing was emptied of contrast, along with any remaining contrast in the bottle into a validated graduated cylinder, establishing contrast remaining end volume. Contrast volume used was calculated as the difference between start and end volumes (contrast start volume − contrast used on table/waste − contrast remaining end volume). Image quality was determined in real time by the physician user as adequate or not to interpret coronary anatomy. In case of inadequate image quality due to AVERT, the system was turned off and the procedure was completed in standard fashion. All such events were recorded. After the procedure, blood testing for SCr was performed at 24 h (or at the time of discharge), at 48 h, and at 72 h. If SCr was still increasing (≥0.2 mg/dl), additional blood draws were obtained at 96 and 120 h. Adverse events were collected at 24 h (or discharge) and during a 30-day telephone visit.
The AVERT system has been previously described (11,12). In brief, the system consists of a contrast modulator and a modulation reservoir disposable component (Online Figure 1). The contrast modulator is used for manual injections only and can be configured to pair with the catheter and contrast medium type used by the physician with a selector pin. The contrast modulator supplies resistance to the modulation reservoir. As contrast medium is manually injected, a portion of the injected contrast medium is diverted to the AVERT modulation reservoir (routed through a 4-way stopcock), while the remaining contrast medium is injected into the patient. Once the injection is complete, the diverted portion of the injected contrast medium is automatically returned to the physician’s injection syringe. The amount of contrast medium diverted depends on the setting selected on the contrast modulator and injection force.
Study objectives and endpoints
This trial had 2 primary effectiveness objectives: 1) to demonstrate whether using the AVERT system for coronary procedures results in a reduction in CMV used; and 2) to demonstrate whether using the AVERT system results in a reduction in the incidence of CI-AKI, defined as an increase in SCr of ≥0.3 mg/dl (26.52 μmol) from baseline to any blood draw within 5 days post-procedurally. The primary safety endpoint was the rate of device-related serious adverse events for subjects treated with the AVERT system within 30 days of the procedure.
Secondary endpoints included assessment of 1) the adequacy of image quality during use of the AVERT device; 2) major adverse events through 30-day post-procedural follow-up, defined as the composite rate of all-cause mortality, myocardial infarction, dialysis-dependent CI-AKI, unplanned rehospitalization, repeat coronary revascularization of the target lesion(s), major bleeding (not related to coronary bypass procedures), and stroke; and 3) changes in kidney function through the 5-day primary effectiveness follow-up period using various measures: absolute SCr increase of ≥0.5 mg/dl (44.2 μmol), relative increases in SCr of ≥25%, ≥100%, and ≥200%, and mean change in eGFR.
The sample size of 578 subjects was estimated on the basis of an assumed control group CI-AKI rate of 22.5% and a treatment group CI-AKI rate of 13.05%, with the Fisher exact test of binomial proportions at a 1-sided alpha level of 0.025, 80% power, and attrition of up to 5%. A 2-stage adaptive design was used to potentially increase the sample size because of the uncertainty regarding the incidence of CI-AKI and the treatment effect. The first stage of the adaptive design included 289 randomized subjects and was used for formal hypothesis testing of the first primary effectiveness endpoint (reduction in CMV). Assuming a mean CMV reduction of 2.2 ± 1.3 ml from a base average of 5.5 ml per injection in the control arm, the sample size for this stage provided 95% power to detect a 42.6% reduction on the basis of a t test of 2 means and a 1-sided alpha level of 0.025. Because of low conditional power (<2%) for the second primary effectiveness endpoint (reduction in CI-AKI) on the basis of the results of the first stage, the sample size for the second stage of the trial was not changed. Enrollment continued to the original planned sample size, as there were no safety concerns and additional data were desired to quantify device performance and safety.
Categorical variables are presented as number (percentage) and continuous variables as mean ± SD. Unless specified, p values are based on the Fisher exact test and 2-sample t test for categorical and continuous variables, respectively. Skewed data were compared using the Wilcoxon signed rank test. A gatekeeping strategy was used for the primary effectiveness objectives to preserve the type I error rate. A formal hypothesis test of the second primary effectiveness endpoint would be made only if the hypothesis test for the first primary effectiveness endpoint resulted in a successful rejection of the null hypothesis. The Fisher combination method was used to combine p values from stage 1 and stage 2 (13). Unless otherwise noted, data presented are based on the combined data from the 2 stages. Principal analyses were performed in the evaluable intention-to-treat population with no imputation for missing data. A sensitivity analysis was performed in the as-treated cohort. P values for the primary effectiveness objectives are 1-sided, with an alpha level of 0.025. The remaining p values, unless otherwise stated, are 2-sided, and a p value of <0.05 was considered to indicate statistical significance. Beyond the primary objective analyses, adjustments were not made for multiple comparisons. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina).
Between January 2014 and July 2015, a total of 578 patients at 39 centers who underwent coronary angiography with or without PCI were randomly assigned to receive periprocedural hydration only (control arm; n = 286) or periprocedural hydration plus intraprocedural use of the AVERT system (AVERT arm; n = 292) (Figure 1). The baseline features of the 2 study groups were well matched (Table 1). The median age was 72 years, 64.9% of patients had diabetes mellitus, and the mean baseline SCr level was 1.6 ± 0.4 mg/dl. No significant differences were present in the rates of risk factors for CI-AKI, including baseline SCr, eGFR, coronary heart disease, congestive heart failure, diabetes mellitus, hypertension, and anemia.
Of the randomized patients, 567 underwent angiographic procedures and received contrast medium (n = 284 in the control arm, n = 283 in the treatment arm). Two patients in the control arm and 9 patients in the treatment arm did not undergo angiography, because of physician, sponsor, or subject withdrawal or nonfulfillment of eligibility criteria (Figure 1). Procedural data are shown in Table 2. PCI was performed in 116 patients (40.8%) in the control arm and 123 (43.5%) in the AVERT arm (p = 0.55). There were no differences in the total volume or duration of periprocedural hydration or in the type of solution used (Online Table 1).
Results from the first stage of the adaptive design (n = 284) exhibited a statistically significant reduction in mean CMV used (87 ± 52.4 ml vs. 102.4 ± 74.1 ml, p = 0.02). The final data analyses from both stages of the trial (n = 567) excluded the 11 patients who did not receive contrast medium. Use of AVERT resulted in a reduction of CMV compared with control subjects (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml, log-transformed p = 0.02). These results correspond to a 15.5% relative reduction (RR) for all procedures and a 22.8% RR in CMV for patients undergoing PCI (113.6 ± 54.8 ml vs. 147.1 ± 81.4 ml, p = 0.001) (Figure 2). The absolute and relative benefit of using AVERT increased with the number of lesions undergoing PCI. When 1 lesion was treated, the contrast medium RR with AVERT compared with control was 14.6% (108.3 ± 55.2 ml vs. 126.8 ± 63.3 ml, p = 0.04); when 2 lesions were treated, the RR was 30.6% (130.4 ± 53.5 ml vs. 188 ± 99.3 ml, p = 0.02); and when 3 lesions were treated, the RR in CMV was 46.4% (124.0 ± 47.9 ml vs. 231.5 ± 96.7 ml, p = 0.01) (Figure 2). The as-treated analysis showed similar results as the intention-to-treat analysis: a significant RR of 16% in CMV was observed in the AVERT arm (85.3 ± 50 ml vs. 101.5 ± 71.2 ml, log-transformed p = 0.0187) The rate of CI-AKI correlated with the CMV used during the procedure (Online Figure 2).
No significant differences in CI-AKI were present between the AVERT and control groups (27.0% vs. 26.6%, respectively, p = 0.70) (Table 3). The relative rates of CI-AKI in the 2 arms were consistent across numerous pre-specified subgroups (Figure 3). Nor was there a significant difference between the groups in CI-AKI when defined as a change in SCr of ≥0.5 mg/dl (7.8% vs. 10%, p = 0.85). The rate of SCr increase ≥25%, ≥100%, and ≥200% compared with baseline was low and similar between the 2 study groups (14.6% vs. 17.0%, p = 0.25; 0.7% vs. 1.1%, p = 0.81; and 0.4% vs. 0%, p = 0.50, respectively) (Table 3).
Image quality in AVERT-treated patients was acceptable in 281 of 283 patients (99.3%), whereas use of the system was discontinued because of device-related image quality issues in 2 of 283 AVERT cases (0.7%). In 12 other cases (4.4%), use of the system was reported to be discontinued for reasons including patient adverse events (n = 2), device-unrelated image quality issue (n = 1), device deficiency (n = 1), user error (n = 1), need for left ventriculography (n = 4), or other reasons (n = 3). One adverse event was reported to be device related, an air embolism that resolved without further intervention. This patient was discharged the same day of procedure. In total, 549 patients were followed through 30 days for safety endpoints. The rates of severe adverse events were comparable between the study groups (Online Table 2).
The main finding of the present randomized trial is that the AVERT system significantly reduced the volume of contrast medium injected in patients undergoing coronary angiographic procedures without compromising the quality of the angiographic images obtained. The observed reduction in CMV used was most evident in patients undergoing PCI. The amount of contrast medium spared with the use of AVERT was directly related to the complexity of the PCI procedure, with 31% and 46% reductions in CMV used when 2 and 3 lesions were treated, respectively. Importantly, the AVERT system resulted in acceptable image quality in >99% of patients. Because the amount of contrast diverted into the reservoir can be fine-tuned by adjusting the resistance of the reservoir line, in most cases the operator was able to compensate for any perceived deterioration in the degree of image opacification during the procedure. In addition, there were no significant differences in major adverse events between the 2 groups, with only 1 possible device-related event reported.
The CMV used during angiographic procedures is a major risk factor for CI-AKI (8). Several recommendations exist for contrast dose management in patients at high risk. For example, it has been suggested that the contrast dose should not exceed 2.5 times the baseline creatinine clearance (14). In case the creatinine clearance is not available at the time of PCI, the maximal acceptable contrast dose may be calculated as 5 ml × body weight (15)/baseline SCr (mg/dl) (16,17). In patients with significant renal impairment (CKD stage 3 or higher), it has been suggested that CMV should not exceed 100 ml for PCI (18). In prior studies, a linear relationship between the CMV used and frequency of CI-AKI has been observed (19).
In the present trial, the AVERT system was tested in a population of patients at high risk for CI-AKI with either severe renal impairment or moderate CKD with 2 additional characteristics conferring higher susceptibility to kidney damage. However, despite the significant reduction of the CMV injected, the rate of CI-AKI was not reduced in the AVERT group. Other studies that have tested automatic injection devices for the reduction of CMV and CI-AKI have also failed to show a clinical benefit despite reducing CMV (20–22). The lack of CI-AKI reduction in this trial may be due to several reasons. The etiology of CI-AKI is multifactorial, and other risk factors may be of equal or greater importance in its pathogenesis, such as patient acuity, cardiogenic shock, and systemic comorbidities (23–25). In addition, a larger volume of contrast medium reduction might be required to substantially reduce the rate of CI-AKI, consistent with prior studies demonstrating that lower CMV in patients undergoing PCI compared with diagnostic angiography only has been associated with greater clinical benefit (14). In this regard, approximately 60% of patients in both arms underwent diagnostic procedures only with lower amounts of CMV, with reduced potential to benefit from the AVERT system in terms of CI-AKI reduction. A higher proportion of patients undergoing PCI, especially of multiple lesions requiring even more contrast medium, might have resulted in a significant reduction in CI-AKI. Unfortunately, our trial was not adequately powered to assess CI-AKI reduction in the PCI only cohort. Since the completion of this trial, a new generation of this product has been introduced and shown in a randomized controlled trial to use 40% less contrast than the control arm, which may prove to be beneficial for decreasing CI-AKI (26).
Despite the absent effect on CI-AKI, CMV reduction is in general desirable and may be safely accomplished with the easy to use AVERT system at low cost. The recent Society for Cardiovascular Angiography and Interventions expert consensus statement on best practices in the cardiac catheterization laboratory emphasizes quality indicators related to CMV reduction and monitoring (27). To date the use of manual injections with a manifold remains the preferred technique in the majority of catheterization laboratories. In particular, manual injection is often favored for interventional procedures, which require low, variable-flow pressure injections (22). Although contrast medium flow rate and maximum injection pressure can be preset in automatic systems, the manual syringe provides constant pressure feedback to the operator that might favor better modulation of the injection. Whipping and displacement of the catheter can also be observed with high-pressure injection systems. Other methods for the limitation of CMV use have been tested. Use of biplane angiography has not been proved to significantly reduce CMV injected (28). In the MOZART (Minimizing Contrast Utilization With IVUS Guidance in Coronary Angioplasty) trial, intravascular ultrasound–guided PCI reduced the CMV used compared with angiography-guided PCI (29). However, IVUS is not widely used and can increase procedure costs and duration. By diverting contrast medium away from the patient during angiographic injections while maintaining image quality, the AVERT system is the only device that has been demonstrated in a randomized clinical trial to reduce CMV use with manual injection.
First, although the patients were blinded to the randomized assignment, the operators were active participants in properly using the AVERT system and as such were unmasked, introducing the potential for bias. Second, although the inclusion criteria were designed to include patients who were likely to undergo PCI, two-thirds of the study population had diagnostic procedures only, which may have reduced the power to elicit a difference in CI-AKI between the groups. Nonetheless, the control CI-AKI rate of 26.6% provided sufficient events to exclude a 29% or greater reduction in the odds of CI-AKI with AVERT. We cannot exclude the possibility of a smaller reduction in CI-AKI with AVERT that might be clinically relevant. Finally, subgroup analysis is inherently underpowered and was not adjusted for multiple comparisons; all such analyses should be considered hypothesis generating. Similarly, the trial was underpowered to detect low-frequency safety events such as need for dialysis.
The AVERT system is an adjunctive device used during manual injection of radiocontrast that in the randomized AVERT trial effectively reduced the CMV injected in patients undergoing diagnostic and interventional coronary procedures, without substantively affecting image quality. The absolute and relative reductions in CMV with AVERT were greatest in patients undergoing PCI rather than diagnostic angiography only, especially PCI of multiple lesions. Despite the reduction of CMV obtained with AVERT, the rate of CI-AKI was not significantly reduced in the present trial. Future trials are needed to determine whether CMV reduction with the AVERT system provides clinical benefit beyond hydration alone in patients at high risk for CI-AKI requiring large CMV use (i.e., complex PCI).
WHAT IS KNOWN? Contrast-induced acute kidney injury (CI-AKI) is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality.
WHAT IS NEW? The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during manual coronary injection. In 578 subjects with either baseline eGFR of 20 to 30 ml/min/1.73 m2 or eGFR of 30 to 60 ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI, use of AVERT resulted in a 15.5% RR in CMV (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml, p = 0.02) and a 22.8% RR in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml, p = 0.001). There were no differences in the rates of CI-AKI (27.0% vs. 26.6%, p = 0.70) between the study groups.
WHAT IS NEXT? Future trials are needed to determine whether CMV reduction with the AVERT system provides clinical benefit beyond hydration alone in patients at high risk for CI-AKI requiring large CMV use.
The authors thank Carlye Kraemer for providing statistical support.
The AVERT trial was sponsored and funded by Osprey Medical. Dr. Mehran has received institutional research grant support from The Medicines Company, Bristol Myers-Squibb, AstraZeneca, and Lilly/Daiichi-Sankyo; is on the advisory board for Janssen (Johnson & Johnson); and has received consulting fees and honoraria from Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Janssen (Johnson & Johnson), and Merck. Dr. Angiolillo has received payments as an individual for consulting fees or honoraria from Amgen, AstraZeneca, Bayer, Biosensors, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen, Merck, PLx Pharma, Pfizer, and Sanofi; and participation in review activities from CeloNova and St. Jude Medical and institutional payments for grants from Amgen, AstraZeneca, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Matsutani Chemical Industry, Merck, Novartis, and Renal Guard Solutions. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- contrast-induced acute kidney injury
- chronic kidney disease
- contrast media volume
- estimated glomerular filtration rate
- percutaneous coronary intervention
- relative reduction
- serum creatinine
- Received February 12, 2018.
- Revision received April 2, 2018.
- Accepted April 5, 2018.
- 2018 American College of Cardiology Foundation
- Giacoppo D.,
- Madhavan M.V.,
- Baber U.,
- et al.
- Mehran R.,
- Aymong E.D.,
- Nikolsky E.,
- et al.
- Wright R.S.,
- Anderson J.L.,
- Adams C.D.,
- et al.
- Prasad A.,
- Ortiz-Lopez C.,
- Kaye D.M.,
- et al.
- Gurm H.S.,
- Seth M.,
- Mehran R.,
- et al.
- Redfors B.,
- Angeras O.,
- Ramunddal T.,
- et al.
- Laskey W.K.,
- Jenkins C.,
- Selzer F.,
- et al.
- Gurm H.S.,
- Dixon S.R.,
- Smith D.E.,
- et al.
- Gurm H.S.,
- Smith D.,
- Share D.,
- et al.
- Hwang J.R.,
- D’Alfonso S.,
- Kostuk W.J.,
- et al.
- Silvain J.,
- Nguyen L.S.,
- Spagnoli V.,
- et al.
- Tsai T.T.,
- Patel U.D.,
- Chang T.I.,
- et al.
- Desch S.,
- Fuernau G.,
- Pöss J.,
- et al.
- Naidu S.S.,
- Aronow H.D.,
- Box L.C.,
- et al.
- Sadick V.,
- Reed W.,
- Collins L.,
- Sadick N.,
- Heard R.,
- Robinson J.
- Mariani J. Jr..,
- Guedes C.,
- Soares P.,
- et al.