Ckd

AHA Scientific Statement

1

Chronic kidney disease (CKD) is frequently encoun-tered among patients presenting with acute coro-nary syndrome (ACS). Recent data from the National Cardiovascular Data RegistryAcute Coronary Treatment and Intervention Outcomes Network (NCDR-ACTION) reported CKD (defined as estimated creatinine clearance [CrCl]

2 Circulation March 24, 2015

As shown in Figure 2, there is a stepwise incremental age-standardized risk for all-cause mortality, cardiovascu-lar events, and hospitalization associated with diminishing renal function.9 Compared with patients with eGFR 60 mLmin11.73 m2, the adjusted hazard for death among patients with eGFR 15 to 29 mLmin11.73 m2 is more than 3-fold higher, and nearly 6 times higher for patients with eGFR 2.5 mg/dL), and 274 777 non-CKD patients.14 Those with advanced CKD and dialysis were less likely to have chest pain on admission (40.4% and 41.1%, respectively) than those without CKD (61.6%). Similar observations were made in the SWEDEHEART registry [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]; however, up to two thirds of patients with stage 4 and 5 CKD in that registry had chest pain at presentation.15 The USRDS-NRMI study also showed that MI patients with advanced CKD and those undergoing dialysis more often had a diagnosis at presentation other than ACS (44% and 47.7%, respectively) compared with patients without CKD (25.8%). Compared with patients without CKD, patients with advanced CKD were also less likely to have ST-segment elevation (15.9% versus 32.5%, respectively) but more likely to have heart failure on presentation (52.2% versus 27.2%, respec-tively) and a higher rate of in-hospital mortality (23% versus 12.6%, respectively).10 Similar differences existed between those with advanced CKD and those undergoing dialysis. The distribution of electrocardiographic presentations varies according to severity of CKD, with fewer STEMIs and more NSTEMI and left bundle branch block among populations with increasingly worse renal function (Figure 3).11,15

An additional consideration in the diagnosis of ACS in patients with CKD is the interpretation of cardiac biomark-ers. Chronic troponin elevations in clinically stable patients with renal failure have been observed and likely represent nonischemic myocardial injury.16 In spite of these chronic troponin elevations in a population of patients with CKD, the National Association of Clinical Biochemistry labora-tory medicine practice guidelines recommend the use of troponins for the diagnosis of MI in patients with CKD pre-senting with symptoms or electrocardiographic changes sug-gestive of myocardial ischemia.17 These guidelines, along with other expert writing groups, advise the importance of a dynamic change in troponin values after presentation in the

Prognosis of CKD by GFRand Albuminuria Categories:

KDIGO 2012

Persistent albuminuria categoriesDescription and range

A1 A2 A3

GFR

cat

egor

ies

(ml/m

in/ 1.

73m2

)D

escr

iptio

n an

d ra

nge

G1 Normal or high 90

G2 Mildly decreased 60-89

G3a 45-59

G3b 30-44

G4 Severely decreased 15-29

G5 Kidney failure 300 mg/g>30 mg/mmol

30-300 mg/g3-30 mg/mmol

Washam et al Pharmacotherapy in CKD Patients With ACS 3

identification of acute MI (AMI) in patients with end-stage renal disease (ESRD), who more frequently have chronically elevated troponin levels.1618

This striking difference in clinical presentation and electro-cardiographic findings has implications for correct diagnosis and subsequent treatment. It has been a subject of great atten-tion that the use of evidence-based therapy is lower among patients with CKD.13,1921 Not only are those with ACS and CKD less likely to receive evidence-based therapies, the atypical clinical presentation of these patients makes it less likely that they will be correctly identified as having ACS on

presentation (and thus would not be considered for appropri-ate therapeutic interventions).

Methods of Estimating Renal Function for Drug Dosing

Whereas the Modification of Diet in Renal Disease (MDRD) equation is widely used for CKD diagnosis and staging, the Cockcroft-Gault (CG) equation has been the most commonly used equation to estimate renal function for dose adjustment of medications.22 Although these equations have limitations, both the CG and MDRD equations have been shown to cor-relate relatively well with measured glomerular filtration rate (GFR),22 but differences in medication dose recommendations have been reported depending on which equation is used.2325 An analysis of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) registry was conducted to compare the CG and MDRD equa-tions with regard to the recommended doses of eptifibatide, tirofiban, and enoxaparin.23 Results of this analysis showed a 20% difference in CKD classification between the 2 equa-tions. The proportion of patients classified as having normal/mild CKD (eGFR 60 mL/min), moderate CKD (eGFR 3059 mL/min), and severe CKD (eGFR


A pooled analysis of 16 710 patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-10A, TIMI-10B, TIMI-14, and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) trials was con-ducted to assess the impact of baseline renal function (SCr and CrCl) on outcomes in patients receiving fibrinolytic therapy.30 A stepwise increase in mortality was seen with worsening renal

function, and rates of intracranial hemorrhage increased with worsening renal function (0.6%, 0.8%, 1.8%, and 3.0% for normal, mildly impaired, moderately impaired, and severely impaired CrCl, respectively; P


and colleagues conducted an observational analysis to assess the prognostic significance of baseline SCr in a study of 352 STEMI patients receiving fibrinolytic therapy.31 In this study, there was no association between baseline SCr and TIMI flow grade after fibrinolytic administration; however, there was a

significant increase in mortality among patients with renal dysfunction (P


severe (eGFR


vascular events (nonfatal MI, nonfatal stroke, or vascular death) by 41% (standard error, 16%). There was no signifi-cant increase in extracranial bleeds, although the absolute number was small (2% in antiplatelet-treated patients versus 2.3% in control subjects).37

Most of the published observational data show similar ben-efits of aspirin therapy in ACS patients across the spectrum of renal function (Table 3). However, one study did find a signifi-cant interaction between discharge aspirin therapy and renal function, with an attenuated benefit with increasing degree of

Table 3. Summary of Aspirin Studies in Patients With ACS and CKD

Study Study Design Population End Points Results

Antithrombotic Trialists Collaboration37

Meta-analysis of randomized trials

287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. The number of hemodialysis patients who received antiplatelet treatment was 1333, whereas the number of hemodialysis patients who received control was 1371.

Serious vascular event (nonfatal MI, nonfatal stroke, or vascular death

Absolute reduction in the risk of serious vascular event in patients with previous MI was 36 (SE 5) per 1000 treated for 2 y and 38 (SE 5) per 1000 treated for 1 mo with AMI. Among individuals undergoing hemodialysis, antiplatelet therapy produced a 41% (SE 16%) proportional reduction in serious vascular events and no significant increase in extracranial bleeds (2% in antiplatelet vs 2.3% in control).

Keough-Ryan et al32

Observational cohort

5549 consecutive patients with ACS surviving to hospital discharge. Renal function classified into normal, >80 mLmin11.73 m2) n=1430; mild CRI, 6080 mLmin11.73 m2 (n=2018); moderate CRI, 3059 mLmin11.73 m2 (n=1795); and severe CRI, 81.5 mL/min (n=524), 63.1 to 81.5 (n=421), 46.2 to 63.1 (n=421), 46.2 not undergoing dialysis (n=310), and chronic dialysis (n=47)

In-hospital mortality Adjusted RR reduction for the combination of in-hospital aspirin and -blocker was 80%, 74.9%, 69%, 64.3%, and 77.9% across the quartiles of corrected creatinine clearance, respectively

Berger et al19 Observational, retrospective analysis of CCP and USRDS

AMI patients: 145 740 patients without ESRD and 1025 patients with ESRD receiving dialysis

Mortality (30 d) Aspirin therapy was associated with a 50% relative reduction in mortality in those receiving dialysis (P


renal dysfunction.32 Although not conducted in ACS patients per se, the United Kingdom Heart and Renal Protection Study and the Dialysis Outcomes and Practice Patterns Study both showed no increased bleeding risk with aspirin therapy among patients receiving hemodialysis, which provides further support for the safety of aspirin in patients with CKD.40,41 Collectively, the available data suggest that aspirin therapy is safe and effec-tive in ACS patients with CKD and should be used in these patients to reduce the risk of death and vascular events.

Clopidogrel, Prasugrel, and TicagrelorCurrent guidelines recommend the use of a P2Y12 receptor inhibitor across the spectrum of ACS presentations.26,42 Data evaluating P2Y12 receptor inhibitors in patients with ESRD are limited, and such information is available predominantly for individuals with moderate or no CKD. Data on the use of P2Y12 receptor inhibitors in ACS patients with CKD are sum-marized in Table 4. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial randomized patients with an ACS without ST-segment elevation to either a 300-mg loading dose of clopidogrel followed by 75 mg per day or placebo. Based on tertiles of renal function, the rela-tive risks (RR) and 95% CIs for the primary composite out-come associated with clopidogrel versus placebo were 0.74 (0.600.93) in the upper third, 0.68 (0.560.84) in the middle third, and 0.89 (0.761.05) in the lower third, with a Pinteraction of 0.11.43,44 In the Clopidogrel for the Reduction of Events During Observation (CREDO, a trial of patients undergoing planned PCI or coronary angiogram)45,46 and the Clopidogrel as Adjunctive Reperfusion TherapyThrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial (a trial of patients with STEMI),47,48 there was a qualitative decline in the efficacy of clopidogrel versus placebo as renal func-tion worsened; the HRs (95% CIs) across renal function were 0.42 (0.260.69), 0.80 (0.511.25), and 1.42 (0.812.45) in CREDO and 0.6 (0.400.90), 0.6 (0.400.70), and 1.0 (0.701.6) in CLARITY-TIMI 28. In a substudy of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, among patients with and without diabetic nephropathy, the HRs (95% CIs) for clopidogrel versus placebo were 0.9 (0.801.0) for those without diabetic nephropathy and 1.1 (0.801.6) for those with diabetic nephropathy.52,53

In terms of safety, more bleeding occurred with clopido-grel than placebo overall; however, there was no signifi-cant interaction based on renal function in CURE, CREDO, or CLARITY-TIMI 28. Within the CHARISMA analysis, the frequency of severe bleeding according to the Global Utilization of Streptokinase and tPA for Occluded Arteries (GUSTO) definition among patients with diabetic nephropa-thy was nonsignificantly higher with clopidogrel than with placebo (2.6% versus 1.5%, P=0.075). In patients without dia-betic nephropathy, there was no difference in GUSTO severe bleeding between patients randomized to clopidogrel versus placebo (1.5% versus 1.3%, P=0.28).53

Prasugrel and ticagrelor are P2Y12 inhibitors that exhibit a more rapid onset, higher degrees of platelet inhibi-tion, and less interpatient variability than clopidogrel. The Trial to Assess Improvement in Therapeutic Outcomes by

Optimizing Platelet Inhibition With PrasugrelThrombolysis in Myocardial Infarction (TRITONTIMI 38) randomized subjects who presented with moderate- to high-risk ACS with scheduled PCI to either prasugrel or clopidogrel. Within this study, the risk reduction associated with prasugrel versus clopidogrel was 20% among those with CrCl 60 mL/min and 14% among those with CrCl


respectively.54,55 In addition, eptifibatide is contraindicated in patients requiring dialysis.54

Abciximab is cleared via the reticuloendothelial system, and no current recommendations exist for dose adjustment for patients with CKD. Data from randomized trials and observa-tional studies on the clinical outcomes of ACS patients with CKD receiving a GP IIb/IIIa receptor antagonist are summa-rized in Table 5.

When used at the time of PCI in ACS patients with CKD, outcomes with the use of GP IIb/IIIa receptor antagonists have been variable. A subgroup analysis of the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial showed the treatment effect of eptifibatide was maintained among those with CrCl 81.3 mL/min), middle tertile (6481.2 mL/min), lower tertile (


Observational cohorts of ACS patients receiving GP IIb/IIIa receptor antagonists at the time of PCI have provided addi-tional insight into use in patients with CKD. Best et al57 assessed patients undergoing PCI in a large registry that divided patients into 3 categories according to creatinine clearance: >70, 5069, or


Freeman et al59 Observational, cohort study

889 patients with ACS, including 310 patients with renal insufficiency defined as CrCl*


patients undergoing PCI who received abciximab.60 Of the 1040 patients included, 44 were classified as having renal insufficiency. The authors reported no significant differences in the rates of in-hospital mortality or nonfatal major adverse cardiac events among patients with renal insufficiency com-pared with those without, although major bleeding occurred more frequently among patients with renal insufficiency (4.5% versus 0.6%; P=0.003). Although limited data are available on the comparative safety and effectiveness of dif-ferent GP IIb/IIIa receptor antagonists among patients with CKD, a subgroup analysis of the Do Tirofiban and ReoPro Give Similar Efficacy Outcome (TARGET) trial compared the outcomes of patients with renal insufficiency undergoing PCI who received either abciximab or tirofiban.61 The 4623 patients with a baseline SCr level available were divided into CrCl quartiles (114 mL/min). Although the rates of both ischemic and bleeding events were higher among patients with lower creatinine clear-ances, there was no interaction between the assigned GP IIb/IIIa receptor antagonist, CrCl, and clinical outcome.

An analysis of the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial provided outcome data on the upstream use of GP IIb/IIIa receptor antagonists among patients presenting with ACS.56 This analysis showed tirofi-ban therapy to be effective in reducing ischemic events, with no evidence of treatment-by-CrCl interaction. Additionally, although decreasing renal function (P


Table 6. Summary of Enoxaparin Studies in Patients With ACS and CKD


ESSENCE-TIMI 11B65

Pooled subgroup analysis of 2 RCTs

7081 NSTE ACS patients enrolled in ESSENCE (n=3171) and TIMI 11B (n=3910) randomized to enoxaparin or UFH. CrCl 30 mL/min was an exclusion in 1 trial (ESSENCE), whereas SCr >2.0 mg/dL was an exclusion in the other (TIMI 11B). Severe renal impairment (CrCl* 30 mL/min) was found in 74 UFH-treated patients and 69 patients receiving enoxaparin (2%). The enoxaparin dose was 1 mg/kg every 12 h.

All-cause death, recurrent MI, and urgent revas-cularization at 43 d

In patients with CrCl 60 mL/min (n=7194), 3160 mL/min (n=3705), 30 mL/min (n=982). In the 3 renal function groups, LMWH was used in 30%, 31%, and 30%, respectively, whereas UFH was used in 22%, 24%, and 28%, respectively.

Mortality (30 d) Worsening renal function was an independent predictor of 30-d mortality and in-hospital major bleeding. Rates of 30-d mortality were significantly lower with LMWH alone than with UFH alone in patients with CrCl >60 mL/min and in those with CrCl 3160 mL/min. No significant difference was seen in patients with CrCl 90 (n=7462), >60 to 90 (n=7203), 3060 (n=3671), and 90 mL/min, 0.78 (0.660.92) for CrCl >60 to 90 mL/min, 0.94 (0.781.12) for CrCl 3060 mL/min, and 0.74 (0.38 1.44) for CrCl 90 mL/min, 1.91 (1.30 2.82) for CrCl >60 to 90 mL/min, 1.73 (1.112.70) for CrCl 3060 mL/min, and 3.60 (0.6719.21) for CrCl


the treatment effects of enoxaparin and UFH.65 Severe renal impairment was identified in 2% of patients in this pooled analysis. There was no statistically significant difference between enoxaparin and UFH with regard to the rates of occurrence of the primary composite end point (18.8% ver-sus 32.4%, respectively; P=0.12) or major hemorrhage (7.5% versus 5.8%, respectively; P=0.56) among patients with CrCl 30 mL/min. The association of CKD with outcomes among patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial who received either enoxapa-rin or UFH was also assessed.68 Patients were placed into 3 groups based on CrCl:


significantly lower in the group receiving fondaparinux (2.4% versus 9.9%, P=0.001).75 Although the rates of major bleeding were lower with fondaparinux across all quartiles of estimated GFR, the difference was most marked among patients with a GFR 90mL/min) or mildly impaired renal function (CrCl >60 mL/min), the pharmacoki-netics of bivalirudin are linear, with an elimination half-life of 25 minutes. The elimination half-life is increased to 34 to 57 minutes in patients with moderate to severe renal impairment (CrCl between 10 and 59 mL/min) and 3.5 hours in patients with renal failure necessitating hemodialysis.7678 For patients with renal insufficiency, the product labeling recommends no reduction in the bolus dose for any degree of renal impair-ment, although the infusion dose of bivalirudin may need to be reduced and anticoagulant status monitored in patients with renal impairment (Table 1).28 Data from randomized trials and observational studies on the use of bivalirudin in ACS patients with CKD are shown in Table 7.

A meta-analysis79 of 3 randomized trials comparing bivali-rudin with UFH at the time of PCI (majority ACS) strati-fied by CrCl >90 mL/min (n=1578), CrCl 90 to 60 mL/min (n=2163), CrCl 59 to 30 mL/min (n=1255), and CrCl


Table 7. Summary of Bivalirudin Studies in Patients With ACS and CKD


Chew et al79 Meta-analysis of 3 trials: the Bivalirudin Angioplasty Study, CACHET trial and REPLACE-1

The trials included patients undergoing PCI receiving bivalirudin or UFH during PCI. Patients were stratified by CrCl* into groups: CrCl >90 mL/min (n=1578), CrCl 6090 mL/min (n=2163), CrCl 3059 mL/min (n=1255), and CrCl 3 mg/dL were excluded from the trials. The indication for PCI was UA in 65% of patients in this analysis.

Primary efficacy end point: composite of death, MI, or urgent revascularization

Adverse ischemic and bleeding events increased with worsening renal function. The ORs (95% CIs) for reduction of the composite ischemic end point with bivalirudin in the 4 CrCl strata were 0.79 (0.521.18), 0.73 (0.530.99), 0.77 (0.55-1.07), and 0.81 (0.125.23), respectively.

Bleeding (definition varied by trial)

The ORs (95% CIs) for reduction in bleeding events were 0.45 (0.210.96), 0.40 (0.091.86), and 0.46 (0.30-0.70) for patients in the CrCl >90 mL/min, CrCl 6090 mL/min, and CrCl 3059 mL/min groups, respectively. The absence of bleeding events in the CrCl 4 mg/dL. In this analysis, patients were grouped based on CrCl*: CrCl 60 mL/min (n=4824) and CrCl


with CrCl


Table 8. Summary of -Blocker Studies in Patients With ACS and CKD


Wali et al94 Post hoc analysis of pooled data from 2 RCTs (CAPRICORN and COPERNICUS)

4217 patients with either post-MI left ventricular dysfunction (CAPRICORN) or severe chronic HF (COPERNICUS) randomized to carvedilol or placebo; 46% of patients were from the CAPRICORN trial. Patients categorized based on eGFR*: eGFR >60 mL/min/1.73 m2 (n=1,651), eGFR 60 (n=2,566). Among those with eGFR 60, 1,116 had an eGFR 60: 0.59 (0.430.81); eGFR 60: 0.78 (0.64-0.95). In the subgroup with eGFR 60: 0.59 (0.42-0.82); eGFR 60: 0.77 (0.620.94).

HF mortality: eGFR >60: 0.58 (0.34-0.99); eGFR 60: 0.68 (0.520.88); in the subgroup with eGFR


ejection fraction 2.5 mg/dL or a serum potassium >5.0 mEq/L. Serious hyperkalemia (6.0 mEq/L) occurred in 5.5% of patients receiving eplerenone com-pared with 3.9% in the placebo group (P=0.002). For patients with CrCl 2.5 mg/dL in men and >2.0 mg/dL in women) or hyperkale-mia (serum potassium >5.0 mEq/L) coexists.87

A post hoc analysis of the EPHESUS trial evaluated serial changes in eGFR related to eplerenone use in patients after ACS. In this analysis, Rossignol et al125 found that 5792 patients assigned to eplerenone 25 to 50 mg/d had a significant decline in their eGFR, with a mean adjusted difference of 1.40.3 mLmin11.73 m2 compared with placebo (P3 mg/dL.

Shlipak et al, 2001122

Observational, retrospective analysis of the CCP database

20 902 Medicare beneficiaries admitted for MI with LVEF


a 1.15-fold increased odds of experiencing a >20% decline in eGFR within the first month compared with placebo (P=0.017).125 However, an eGFR 60 mLmin11.73 m2 was not associated with early worsening renal function, and there was no interaction between worsening renal function and the favorable effects of eplerenone on cardiovascular death or hospitalization (P=0.77 for interaction) and hospitalization for heart failure (P=0.82 for interaction).125StatinsA large body of literature supports of the use of statins after an ACS to reduce the risk of death or vascular events. Current guidelines recommend statins regardless of baseline low-den-sity lipoprotein level in all ACS patients in the absence of con-traindications.26,27 With regard to CKD patients, those receiving chronic dialysis in particular, the use of statins has been more controversial. No randomized controlled trials have assessed the safety and efficacy of statins in patients with ACS and

CKD. Furthermore, patients with SCr >2 mg/dL were excluded from the original ACS randomized trials of early initiation of statins.126,127 However, in primary prevention, randomized tri-als of statin therapy in patients with CKD have yielded mixed results.128131 Early studies found no benefit of statin therapy among patients with CKD (mostly dialysis dependent),129131 which led to speculation that in ESRD, there may be a more advanced atherosclerotic state that leads to more sudden deaths caused by arrhythmias than among patients without ESRD. However, more recently, the largest of these studies, the Study of Heart and Renal Protection (SHARP), included patients with CKD both on dialysis and not on dialysis and showed a benefit of simvastatin plus ezetimibe therapy on the risk of the primary composite end point of first major atherosclerotic event (RR, 0.83; 95% CI, 0.740.94; P=0.0021), although no statistically significant difference was observed for the risk of vascular death (RR, 0.93; 95% CI, 0.801.07).128 Although

Table 10. Summary of Statin Studies in Patients With ACS and CKD


Lim et al132 Observational, retrospective analysis of KAMIR cohort

12 865 AMI patients; 3256 patients with AMI and renal insufficiency (eGFR


statin trials in ACS have largely excluded patients with CKD, observational studies have evaluated the safety and efficacy of statins in these patients.32,132134 The data on the use of statins in ACS patients with CKD are summarized in Table 10. The Korea Acute Myocardial Infarction Registry (KAMIR) study was observational and evaluated 12 865 patients with MI, 3256 of whom had renal dysfunction (defined as eGFR


Disclosures

Writing Group Disclosures

Writing Group Member Employment Research Grant

Other Research Support

Speakers Bureau/

HonorariaExpert

WitnessOwnership

InterestConsultant/Advisory

Board Other

Jeffrey B. Washam

Duke Heart Center None None None None None None None

L. Kristin Newby

Duke University Medical Center

Amylin*; Bristol Myers- Squibb*; Duke; Eli Lilly & Co*;

GlaxoSmithKline; Johnson & Johnson*; Merck & Co; NIH; Regado Biosciences*

None None None None Amgen; AstraZeneca*; Cubist*; Daiichi

Sankyo*; Genentech*;

GlaxoSmithKline*; Novartis*

American Heart Journal*; Society of Chest Pain Centers*;

JAHA*

Amber L. Beitelshees

University of Maryland None None None None None None None

Mauricio G. Cohen

University of Miami Miller School of Medicine

None None None None None Daiichi-Sankyo; AstraZeneca; The Medicines

Company*

None

Timothy D. Henry

Cedars-Sinai Heart Institute

None None None None None Daiichi Sankyo*; Eli Lilly*; The

Medicines Company*

None

Charles A. Herzog

Hennepin Healthcare System, Inc

AHRQ DEcIDE Network; NIH/NIDDK; NHLBI

Affymax*; Amgen; Gilead; Johnson &

Johnson

CardioRenal Society of

America & NKF of Arizona*; Greenfield

Health System*; Keryx*

None Boston Scientific*; Cambridge

Heart*; Johnson & Johnson*;

Merck*

Abbott*; Affymax*; Amgen;

CorMedix*; FibroGen*;

Fresenius*; Keryx*; GlaxoSmithKline*;

AbbVie*

None

Navin K. Kapur Tufts Medical Center None None None None None None None

Jessica L. Mega

Brigham & Womens Hospital

Daiichi Sankyo; AstraZeneca

None None None None Bayer*; Janssen*; Portola*

None

Venu Menon Cleveland Clinic AstraZeneca None None None None None None

Robert L. Page II

University of Colorado School of Pharmacy

None None None None None None None

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the persons gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition.

*Modest.Significant.

by guest on March 22, 2015http://circ.ahajournals.org/Downloaded from


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Reviewer Disclosures

Reviewer Employment Research GrantOther Research

SupportSpeakers Bureau/

Honoraria Expert WitnessOwnership

InterestConsultant/

Advisory Board Other

Sripal Bangalore New York University NHLBI (PI of the ISCHEMIA CKD

trial)

None None None None None None

Gregory Barsness Mayo Clinic None None None None None None None

David Charytan Brigham and Womens Hospital

NIH Medtronic None Fresenius None Keryx*; Medtronic*

None

Peter McCullough Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton

Heart and Vascular Hospital, Dallas, TX, The Heart Hospital, Plano, TX

None None None None None None None

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the persons gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition.

*Modest.Significant.



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KEY WORDS: AHA Scientific Statements acute coronary syndrome chronic kidney disease kidney disease pharmacotherapy


Henry, Navin K. Kapur, Jessica L. Mega, Venu Menon, Robert L. Page II and L. Kristin NewbyJeffrey B. Washam, Charles A. Herzog, Amber L. Beitelshees, Mauricio G. Cohen, Timothy D.

Syndrome: A Scientific Statement From the American Heart AssociationPharmacotherapy in Chronic Kidney Disease Patients Presenting With Acute Coronary

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