Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
Conditions: Heart Failure, Systolic, Frailty
Sponsor: Brigham and Women's Hospital

Prospective Monitoring of Angiotensin Receptor Blocker Neprilysin Inhibitor 
in Older Adults with Heart Failure and Frailty 
February 11, 2021 
NCT04743063 

 
1 
STUDY PROTOCOL 
 
Prospective Monitoring of Angiotensin Receptor Blocker Neprilysin Inhibitor  
in Older Adults with Heart Failure and Frailty 
 
Preparation or Update Date:  
 
01/14/2021

2 
Protocol Revision Summary 
Date 
Summary of Changes 
01/14/2021 
Protocol preparation for study registration 

3 
BACKGROUND 
1. Angiotensin receptor blocker neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto (1))
a.
Approved in July 7, 2015
b. Indication: HF with reduced ejection fraction
2. PARADIGM-HF trial; ARNI vs enalapril (2) 
a.
N=8442, follow-up 2.3 years
b. Composite of cardiovascular death and HF hospitalization: 21.8% vs 26.5%
c.
Safety endpoints: hypotension (14.0% vs 9.2%), renal failure (3.3% vs 4.5%),
hyperkalemia (16.1% vs 17.3%), angioedema (0.4% vs 0.2%)
3. 2017 ACC/AHA/HFSA guidelines for management of heart failure (3)
a.
The clinical strategy of inhibition of the renin-angiotensin system with ACE
inhibitors (Level of Evidence: A), OR ARBs (Level of Evidence: A), OR ARNI
(Level of Evidence: B-R) in conjunction with evidence-based beta blockers, and
aldosterone antagonists in selected patients, is recommended for patients with chronic
HFrEF to reduce morbidity and mortality.
b. The use of ACE inhibitors is beneficial for patients with prior or current symptoms of
chronic HFrEF to reduce morbidity and mortality (Level of Evidence: A).  Although
the use of an ARNI in lieu of an ACE inhibitor for HFrEF has been found to be
superior, for those patients for whom ARNI is not appropriate, continued use of an
ACE inhibitor for all classes of HFrEF remains strongly advised.
c.
The use of ARBs to reduce morbidity and mortality is recommended in patients with
prior or current symptoms of chronic HFrEF who are intolerant to ACE inhibitors
because of cough or angioedema (Level of Evidence: A). Head-to-head comparisons
of an ARB versus ARNI for HF do not exist. For those patients for whom an ACE
inhibitor or ARNI is inappropriate, use of an ARB remains advised.
d. In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an
ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce
morbidity and mortality (Level of Evidence: B).

4 
e.
ARNI should not be administered concomitantly with ACE inhibitors or within 36
hours of the last dose of an ACE inhibitor (Level of Evidence: B). Oral neprilysin
inhibitors, used in combination with ACE inhibitors can lead to angioedema and
concomitant use is contraindicated and should be avoided.
f.
ARNI should not be administered to patients with a history of angioedema (Level of
Evidence: C).
4. 2021 ACC/AHA/HFSA focused update (4)
a.
For patients with newly diagnosed Stage C HFrEF, a beta-blocker and an
ACEI/ARB/ARNI should be started in any order. Each agent should be up-titrated to
maximally tolerated or target dose. Initiation of a beta-blocker is better tolerated
when patients are dry and an ACEI/ARB/ARNI when patients are wet.
STUDY OVERVIEW AND DESIGN 
1. Study aims: To emulate a prospective surveillance of the effectiveness and safety of ARNI vs
a comparator (ARB) in older adults with HFrEF and different frailty status.
2. Data source(s): Data from 2014 up to 2020 will be used.
a.
Medicare Database
b. Optum Database
c.
MarketScan Research Database
3. Sequential cohort monitoring design (see Figure 1): The monitoring analysis will include 1)
retrospective analysis of available data (2015-2017) at the time of first analysis (January
2021) and 2) prospective analysis of new data (2018-2020) as they become available to the
researchers.  Within each database, we will emulate biannual updating of data by creating a
propensity score (PS)-matched cohort of new users every 6-month interval, beginning on the
first marketing of ARNI (July 7, 2015-December 31, 2015, and 6-month intervals
afterwards).  Each sequential cohort will be followed for development of the outcomes of

&!
interest.  Outcome analysis will be performed at a pre-specified 6-month interval 
(prospective analysis).  The surveillance will be performed by frailty status (frail vs non-frail) 
at the time of drug initiation.  The results from each database will be pooled using fixed-
effects meta-analysis (assuming low heterogeneity across the databases). 
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.<9;='!8!9B4<@8:'
1. Study population (see Figure 2) is created for each calendar interval.
2. Initiation of ARNI or comparator (ARB)
a.
ARB: any of azilsartan, candesartan, eprosartan, Irbesartan, losartan, Olmesartan,
telmisartan, valsartan
b. Index date (day 0): prescription fill from July 7, 2015
2015  
Jul-Dec
2016 
Jan-Jun
2016 
Jul-Dec
2017 
Jan-Jun
2017 
Jul-Dec
2018 
Jan-Jun
2018 
Jul-Dec
2019 
Jan-Jun
2019 
Jul-Dec
2020 
Jan-Jun
2020 
Jul-Dec
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Cohort 6
Cohort 7
Cohort 8
Cohort 9
Cohort 10
Cohort 11
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initiators
Initial  
Analysis
Interim  
Analysis 2
Interim  
Analysis 4
Final 
Analysis
Retrospective analysis
Prospective analysis
Protocol
Interim  
Analysis 5
Interim  
Analysis 3
Interim  
Analysis 1

6 
3. Assessment of eligibility (eligibility assessment window: [-365, 0] days) – See Appendix for
list of codes.
a.
Continuous enrollment for medical and drug insurance (Part A, B, and D)
b. Diagnosis of HF (outpatient diagnosis x2 or inpatient x1)
c.
Reduced EF (<45%) algorithm (5)
d. No prior use of ARNI or comparator (exposure wash-out window: [-365, -1] days)
e.
No recent HF hospitalization, defined as HF diagnosis (Appendix) in the primary
position in the inpatient dataset (outcome wash-out window: [-60, 0] days)
f.
No recent nursing facility stay, defined as any of the following claims in [-60, 0] days
i. Place of service: 31 (skilled nursing facility), 32 (nursing facility), 33
(custodial care facility)
ii. CPT codes: 99301, 99302, 99303, 99311, 99312, 99313, 99315, 99316,
99379, 99380, G0066
g. Excluded if age <65 years or exposure to both drugs on day 0
h. Contraindication to either drug (exclusion assessment window: [-60, 0] days, unless
specified otherwise)
i. Hypotension
ii. Chronic kidney disease stage IV or V or dialysis
iii. Acute kidney injury
iv. Hyperkalemia
v. Angioedema: [-beginning of data, 0] days
i.
If a patient meets the above-mentioned eligibility criteria more than once, only the
first record will be included.

(!
G37C,0&MO&!2CB>&B0.376&-C2;360&8-,&1-N/F,F2340&08801234060..&F6B&.F802>&F6F;>.3.&
C?4.9(?C?:<.'
1. Exposure to ARNI or comparator
a.
ARNI: sacubitril/valsartan (Entresto)
b. ARB (comparator): any of azilsartan, candesartan, eprosartan, Irbesartan, losartan,
Olmesartan, telmisartan, valsartan
c.
Note: prior ACEI use (commonly used for hypertension and HFrEF) is allowed.  This
choice will resemble a clinic situation that involves switching from ACEI to ARB or
to ARNI.
d. Exposure risk window and gap between treatments allowed: 7 days (primary analysis)
or 14 days (sensitivity analysis)
Eligibility Assessment Window (gap in medical and drug coverage)
Days [-365, 0]
Cohort Entry Date
(First prescription of study drugs)
Day 0
Exclusion Assessment Window (Age!65, initiate both drugs)
Days [0, 0]
Time
Washout Window (exposure)
Days [-365, -1]
Censoring: the earliest of the following events 
! Outcome of interest
! Switching or discontinuation of study drugs
! Death not due to the outcome of interest
! Disenrollment
! End of the study period
Covariate Assessment Window (Age, sex)
Days [0, 0]
Follow-up Window
Days [0, Censorc]
Follow up Window
Days [1, Censor event]
Covariate Assessment Window (Diagnosis, Drugs, and Frailty)
Days [-365, 0]
Washout Window (outcome)
Days [-60, 0]
Exclusion Assessment Window 
Days [-60, 0]

8 
2. Outcomes
a.
Effectiveness endpoint:
i. Primary: a composite of all-cause death or HF hospitalization
•
Note cardiovascular death was not used because National Death
Index data were only available up to 2016.  Instead, all-cause death
was used.
•
HF hospitalization is defined as HF diagnosis primary position in
the inpatient dataset
ii. Secondary: individual components separately
b. Safety endpoint:
i. Primary: a composite of SAE, defined as any hospitalization or ED visit
due to diagnosis codes in the primary position:
•
hypotension
•
acute kidney injury/acute kidney failure
•
hyperkalemia
•
angioedema
ii. Secondary: individual components
3. Covariates
a.
Sociodemographic information: age, sex, race, dual eligibility
b. Diseases: Chronic Conditions Data Warehouse (CCW) chronic conditions (see Table
2), provided in the Medicare Beneficiary Summary File (first date of satisfying the
claims-based algorithm for individual conditions is available; considered present if
this date is earlier than the index date)
c.
Prescription drugs: ATC3 classes with prevalence threshold >1% in a representative
Medicare sample
d. Gagne combined comorbidity score (6)
e.
Claims-based frailty index (7): Frailty status will be defined as non-frail if <0.20 or
frail if ≥0.20

9 
Table 2. CCW Chronic Conditions (8) 
Acquired Hypothyroidism 
Chronic Kidney Disease 
Acute Myocardial Infarction
Chronic Obstructive Pulmonary Disease 
Alzheimer's Disease, Related Disorders, or 
Senile Dementia
Depression
Anemia 
Diabetes 
Asthma 
Glaucoma 
Atrial Fibrillation 
Hip / Pelvic Fracture
Benign Prostatic Hyperplasia 
Hyperlipidemia 
Cancer (any of the following): 
Cancer, Colorectal 
Cancer, Endometrial 
Cancer, Breast 
Cancer, Lung 
Cancer, Prostate 
Hypertension 
Ischemic Heart Disease 
Osteoporosis 
Rheumatoid Arthritis / Osteoarthritis 
Stroke / Transient Ischemic Attack 
Cataract 

10 
STATISTICAL ANALYSIS 
Estimation of treatment effectiveness and safety within each database 
1. PS-matched cohorts: Within each surveillance cohort by frailty status (frail vs non-frail), we
will use logistic regression that estimates the probability of receiving the drug of interest as a
function of sociodemographic characteristics, diseases, prescription drugs, comorbidity
index, and frailty index.  Note that PS model will be fit separately by frailty status.  We will
perform a 1:1 ratio nearest-neighbor PS matching, with a caliper of 0.2 of the standard
deviation of the logit PS (9).  We will evaluate balance in covariates using standard mean
difference (<0.1 is considered adequate balance) within each surveillance cohort.
2. Primary analysis for effectiveness and safety: For time-to-event analysis of the effectiveness
and safety endpoints, we will use Cox proportional hazards regression to estimate the hazard
ratios (HR) and 95% confidence intervals (CI) by frailty status (frail vs non-frail).  The
follow-up will begin on day 1 and end on the day of development of the effectiveness or
safety endpoints or the earliest of the following censoring events: switching or
discontinuation of the study drug, death not due to the outcome of interest, disenrollment,
and end of data period (see Figure 2).  Proportional hazards assumptions will be checked
using Schoenfeld residuals.
3. Subgroup analyses for primary effectiveness and safety endpoints will be conducted by
frailty status (frail vs non-frail):
a.
age (65-74 years vs ≥75 years)
b. sex
c.
race (black or non-black)
d. dual eligibility for Medicaid
e.
major multimorbidity burden/pattern (informed by latent class analysis)
f.
dementia (CCW definition)
g. HF hospitalization status (≥2 or <2 in the past year)

11 
4. Secondary analyses will be conducted by frailty status (frail vs non-frail):
a.
secondary endpoints (individual components of primary effectiveness and safety
composite endpoints)
5. Sensitivity analysis for primary effectiveness and safety endpoints will be conducted by
frailty status (frail vs non-frail):
a.
“intention-to-treat” analysis with a maximum follow-up time of 1 and 2 years from
the index date
b. exposure risk window or grace period of 14 days
6. Adjustment for multiple testing in detecting signal: We will use the maximum sequential
probability ratio testing (maxSPRT) procedure to keep the overall type-1 error rate of 0.05.
(10)
Estimation of the pooled treatment effectiveness and safety 
7. The treatment effect estimates from 3 databases will be combined using meta-analysis
techniques.  We will examine the heterogeneity of treatment effect using Cochrane Q
statistics and I-square statistics.  If there is no statistically significant evidence of treatment
effect heterogeneity, we will use inverse probability fixed-effects model to pool the database-
specific estimates.  If there is significant treatment effect heterogeneity, we will use random-
effects model.
8. Reporting of prospective monitoring results: When a statistically significant signal is
detected from the pooled analysis for the primary endpoints of effectiveness or safety from
pre-specified interim analysis or at the end of the data period (12/31/2020), the findings will
be reported

12 
REFERENCES 
1.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207620s013lbl.pdf. U.S.
Food and Drug Administration; 2021. 
2.
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al.
Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med.
2014;371(11):993-1004.
3.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Colvin MM, et al. 2017
ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the
Management of Heart Failure: A Report of the American College of
Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and
the Heart Failure Society of America. Circulation. 2017;136(6):e137-e61.
4.
Maddox TM, Januzzi JL, Allen LA, Breathett K, Butler J, Davis LL, et al. 2021 Update
to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure
Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection
Fraction. Journal of the American College of Cardiology.0(0).
5.
Desai RJ, Lin KJ, Patorno E, Barberio J, Lee M, Levin R, et al. Development and
Preliminary Validation of a Medicare Claims-Based Model to Predict Left Ventricular
Ejection Fraction Class in Patients With Heart Failure. Circ Cardiovasc Qual Outcomes.
2018;11(12):e004700.
6.
Combined Comorbidity Score for Claims Data [Internet]. Available from:
https://www.drugepi.org/dope/software
7.
Claims-Based Frailty Index [Internet]. 2020 [cited December 1, 2020]. Available from:
https://dataverse.harvard.edu/dataverse/cfi/.
8.
Chronic Conditions Data Warehouse [Internet]. 2020. Available from:
https://www2.ccwdata.org/web/guest/condition-categories/
9.
Austin PC. Optimal caliper widths for propensity-score matching when estimating
differences in means and differences in proportions in observational studies. Pharm Stat.
2011;10(2):150-61.

13 
10.
Brown JS, Kulldorff M, Chan KA, Davis RL, Graham D, Pettus PT, et al. Early detection
of adverse drug events within population-based health networks: application of sequential
testing methods. Pharmacoepidemiology and Drug Safety. 2007;16(12):1275-84.

ICD10
ICD9 ICD10 Description
ICD9 Description
I120
40391 Hypertensive chronic kidney disease with stage 5 chronic 
kidney disease or end stage renal disease
Hypertensive chronic kidney disease, unspecified, with chronic kidney disease stage V 
or end stage renal disease
N170
5845
Acute kidney failure with tubular necrosis
Acute kidney failure with lesion of tubular necrosis
N171
5846
Acute kidney failure with acute cortical necrosis
Acute kidney failure with lesion of renal cortical necrosis
N172
5847
Acute kidney failure with medullary necrosis
Acute kidney failure with lesion of renal medullary [papillary] necrosis
N178
5848
Other acute kidney failure
Acute kidney failure with other specified pathological lesion in kidney
N179
5849
Acute kidney failure, unspecified
Acute kidney failure, unspecified
N19
586
Unspecified kidney failure
Renal failure, unspecified
Z4931
V560
Encounter for adequacy testing for hemodialysis
Encounter for extracorporeal dialysis
ICD10
ICD9 ICD10 Description
ICD9 Description
T783XXA9951
Angioneurotic edema, initial encounter
Angioneurotic edema, not elsewhere classified
T783XXDV5889 Angioneurotic edema, subsequent encounter
Other specified aftercare
T783XXS9099
Angioneurotic edema, sequela
Late effect of other and unspecified external causes
ICD10
ICD9 ICD10 Description
ICD9 Description
E1021
25043 Type 1 diabetes mellitus with diabetic nephropathy
Diabetes with renal manifestations, type I [juvenile type], uncontrolled
E1022
25041 Type 1 diabetes mellitus with diabetic chronic kidney disease
Diabetes with renal manifestations, type I [juvenile type], not stated as uncontrolled
E1029
25041 Type 1 diabetes mellitus with other diabetic kidney 
complication
Diabetes with renal manifestations, type I [juvenile type], not stated as uncontrolled
E1065
25043 Type 1 diabetes mellitus with hyperglycemia
Diabetes with renal manifestations, type I [juvenile type], uncontrolled
E1121
25042 Type 2 diabetes mellitus with diabetic nephropathy
Diabetes with renal manifestations, type II or unspecified type, uncontrolled
E1122
25040 Type 2 diabetes mellitus with diabetic chronic kidney disease
Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
E1129
25040 Type 2 diabetes mellitus with other diabetic kidney 
complication
Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
E1165
25042 Type 2 diabetes mellitus with hyperglycemia
Diabetes with renal manifestations, type II or unspecified type, uncontrolled
E1321
25040 Other specified diabetes mellitus with diabetic nephropathy
Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
E1322
25040 Other specified diabetes mellitus with diabetic chronic kidney 
disease
Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
E1329
25040 Other specified diabetes mellitus with other diabetic kidney 
complication
Diabetes with renal manifestations, type II or unspecified type, not stated as uncontrolled
I120
40391 Hypertensive chronic kidney disease with stage 5 chronic 
kidney disease or end stage renal disease
Hypertensive chronic kidney disease, unspecified, with chronic kidney disease stage V 
or end stage renal disease
I129
40390 Hypertensive chronic kidney disease with stage 1 through 
stage 4 chronic kidney disease, or unspecified chronic kidney 
disease
Hypertensive chronic kidney disease, unspecified, with chronic kidney disease stage I 
through stage IV, or unspecified
I130
40491 Hypertensive heart and chronic kidney disease with heart 
failure and stage 1 through stage 4 chronic kidney disease, or 
unspecified chronic kidney disease
Hypertensive heart and chronic kidney disease, unspecified, with heart failure and with 
chronic kidney disease stage I through stage IV, or unspecified
I1310
40490 Hypertensive heart and chronic kidney disease without heart 
failure, with stage 1 through stage 4 chronic kidney disease, or 
unspecified chronic kidney disease
Hypertensive heart and chronic kidney disease, unspecified, without heart failure and 
with chronic kidney disease stage I through stage IV, or unspecified
I1311
40492 Hypertensive heart and chronic kidney disease without heart 
failure, with stage 5 chronic kidney disease, or end stage renal 
disease
Hypertensive heart and chronic kidney disease, unspecified, without heart failure and 
with chronic kidney disease stage V or end stage renal disease
I132
40493 Hypertensive heart and chronic kidney disease with heart 
failure and with stage 5 chronic kidney disease, or end stage 
renal disease
Hypertensive heart and chronic kidney disease, unspecified, with heart failure and 
chronic kidney disease stage V or end stage renal disease
N181
5851
Chronic kidney disease, stage 1
Chronic kidney disease, Stage I
N182
5852
Chronic kidney disease, stage 2 (mild)
Chronic kidney disease, Stage II (mild)
N183
5853
Chronic kidney disease, stage 3 (moderate)
Chronic kidney disease, Stage III (moderate)
N184
5854
Chronic kidney disease, stage 4 (severe)
Chronic kidney disease, Stage IV (severe)
N189
5859
Chronic kidney disease, unspecified
Chronic kidney disease, unspecified
N250
5880
Renal osteodystrophy
Renal osteodystrophy
N251
5881
Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus
N2581
58881 Secondary hyperparathyroidism of renal origin
Secondary hyperparathyroidism (of renal origin)
N2589
58889 Other disorders resulting from impaired renal tubular function Other specified disorders resulting from impaired renal function
N259
5889
Disorder resulting from impaired renal tubular function, 
unspecified
Unspecified disorder resulting from impaired renal function
ICD10
ICD9 ICD10 Description
ICD9 Description
I953
45821 Hypotension of hemodialysis
Hypotension of hemodialysis
N185
5855
Chronic kidney disease, stage 5
Chronic kidney disease, Stage V
Acute kidney injury Dx
Angioedema Dx
Chronic kidney disease stage IV or V or dialysis Dx
End-Stage Renal Disease (ESRD) Dx
Appendix 

N186
5856
End stage renal disease
End stage renal disease
T82818
A
99673 Embolism due to vascular prosthetic devices, implants and 
grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T82828
A
99673 Fibrosis due to vascular prosthetic devices, implants and 
grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T82838
A
99673 Hemorrhage due to vascular prosthetic devices, implants and 
grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T82848
A
99673 Pain due to vascular prosthetic devices, implants and grafts, 
initial encounter
Other complications due to renal dialysis device, implant, and graft
T82858
A
99673 Stenosis of other vascular prosthetic devices, implants and 
grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T82868
A
99673 Thrombosis due to vascular prosthetic devices, implants and 
grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T82898
A
99673 Other specified complication of vascular prosthetic devices, 
implants and grafts, initial encounter
Other complications due to renal dialysis device, implant, and graft
T85611
A
99656 Breakdown (mechanical) of intraperitoneal dialysis catheter, 
initial encounter
Mechanical complication due to peritoneal dialysis catheter
T85621
A
99656 Displacement of intraperitoneal dialysis catheter, initial 
encounter
Mechanical complication due to peritoneal dialysis catheter
T85631
A
99656 Leakage of intraperitoneal dialysis catheter, initial encounter
Mechanical complication due to peritoneal dialysis catheter
T85691
A
99656 Other mechanical complication of intraperitoneal dialysis 
catheter, initial encounter
Mechanical complication due to peritoneal dialysis catheter
T8571X
A
99668 Infection and inflammatory reaction due to peritoneal dialysis 
catheter, initial encounter
Infection and inflammatory reaction due to peritoneal dialysis catheter
T8610
99681 Unspecified complication of kidney transplant
Complications of transplanted kidney
T8611
99681 Kidney transplant rejection
Complications of transplanted kidney
T8612
99681 Kidney transplant failure
Complications of transplanted kidney
T8613
99681 Kidney transplant infection
Complications of transplanted kidney
T8619
99681 Other complication of kidney transplant
Complications of transplanted kidney
Z4822
V420
Encounter for aftercare following kidney transplant
Kidney replaced by transplant
Z4901
V561
Encounter for fitting and adjustment of extracorporeal dialysis 
catheter
Fitting and adjustment of extracorporeal dialysis catheter
Z4902
V562
Encounter for fitting and adjustment of peritoneal dialysis 
catheter
Fitting and adjustment of peritoneal dialysis catheter
Z4931
V5631 Encounter for adequacy testing for hemodialysis
Encounter for adequacy testing for hemodialysis
Z4932
V568
Encounter for adequacy testing for peritoneal dialysis
Encounter for other dialysis
Z9115
V4512 Patient's noncompliance with renal dialysis
Noncompliance with renal dialysis
Z940
V420
Kidney transplant status
Kidney replaced by transplant
Z992
V4511 Dependence on renal dialysis
Renal dialysis status
ICD10
ICD9 ICD10 Description
ICD9 Description
03130JD 3993
Bypass Right Subclavian Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03130Z
D
3927
Bypass Right Subclavian Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03140JD 3993
Bypass Left Subclavian Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03140Z
D
3927
Bypass Left Subclavian Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
031509
V
3927
Bypass Right Axillary Artery to Superior Vena Cava with 
Autologous Venous Tissue, Open Approach
Arteriovenostomy for renal dialysis
03150A
V
3927
Bypass Right Axillary Artery to Superior Vena Cava with 
Autologous Arterial Tissue, Open Approach
Arteriovenostomy for renal dialysis
03150JD 3993
Bypass Right Axillary Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03150JV 3927
Bypass Right Axillary Artery to Superior Vena Cava with 
Synthetic Substitute, Open Approach
Arteriovenostomy for renal dialysis
03150K
V
3927
Bypass Right Axillary Artery to Superior Vena Cava with 
Nonautologous Tissue Substitute, Open Approach
Arteriovenostomy for renal dialysis
03150Z
D
3927
Bypass Right Axillary Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03150Z
V
3927
Bypass Right Axillary Artery to Superior Vena Cava, Open 
Approach
Arteriovenostomy for renal dialysis
End-Stage Renal Disease (ESRD) Px
Appendix

031609
V
3927
Bypass Left Axillary Artery to Superior Vena Cava with 
Autologous Venous Tissue, Open Approach
Arteriovenostomy for renal dialysis
03160A
V
3927
Bypass Left Axillary Artery to Superior Vena Cava with 
Autologous Arterial Tissue, Open Approach
Arteriovenostomy for renal dialysis
03160JD 3993
Bypass Left Axillary Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03160JV 3927
Bypass Left Axillary Artery to Superior Vena Cava with 
Synthetic Substitute, Open Approach
Arteriovenostomy for renal dialysis
03160K
V
3927
Bypass Left Axillary Artery to Superior Vena Cava with 
Nonautologous Tissue Substitute, Open Approach
Arteriovenostomy for renal dialysis
03160Z
D
3927
Bypass Left Axillary Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03160Z
V
3927
Bypass Left Axillary Artery to Superior Vena Cava, Open 
Approach
Arteriovenostomy for renal dialysis
031709
V
3927
Bypass Right Brachial Artery to Superior Vena Cava with 
Autologous Venous Tissue, Open Approach
Arteriovenostomy for renal dialysis
03170A
V
3927
Bypass Right Brachial Artery to Superior Vena Cava with 
Autologous Arterial Tissue, Open Approach
Arteriovenostomy for renal dialysis
03170JD 3993
Bypass Right Brachial Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03170JV 3927
Bypass Right Brachial Artery to Superior Vena Cava with 
Synthetic Substitute, Open Approach
Arteriovenostomy for renal dialysis
03170K
V
3927
Bypass Right Brachial Artery to Superior Vena Cava with 
Nonautologous Tissue Substitute, Open Approach
Arteriovenostomy for renal dialysis
03170Z
D
3927
Bypass Right Brachial Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03170Z
V
3927
Bypass Right Brachial Artery to Superior Vena Cava, Open 
Approach
Arteriovenostomy for renal dialysis
031809
V
3927
Bypass Left Brachial Artery to Superior Vena Cava with 
Autologous Venous Tissue, Open Approach
Arteriovenostomy for renal dialysis
03180A
V
3927
Bypass Left Brachial Artery to Superior Vena Cava with 
Autologous Arterial Tissue, Open Approach
Arteriovenostomy for renal dialysis
03180JD 3993
Bypass Left Brachial Artery to Upper Arm Vein with 
Synthetic Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03180JV 3927
Bypass Left Brachial Artery to Superior Vena Cava with 
Synthetic Substitute, Open Approach
Arteriovenostomy for renal dialysis
03180K
V
3927
Bypass Left Brachial Artery to Superior Vena Cava with 
Nonautologous Tissue Substitute, Open Approach
Arteriovenostomy for renal dialysis
03180Z
D
3927
Bypass Left Brachial Artery to Upper Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03180Z
V
3927
Bypass Left Brachial Artery to Superior Vena Cava, Open 
Approach
Arteriovenostomy for renal dialysis
03190JF 3993
Bypass Right Ulnar Artery to Lower Arm Vein with Synthetic 
Substitute, Open Approach
Insertion of vessel-to-vessel cannula
03190ZF 3927
Bypass Right Ulnar Artery to Lower Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
031A0J
F
3993
Bypass Left Ulnar Artery to Lower Arm Vein with Synthetic 
Substitute, Open Approach
Insertion of vessel-to-vessel cannula
031A0Z
F
3927
Bypass Left Ulnar Artery to Lower Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
031B0JF 3994
Bypass Right Radial Artery to Lower Arm Vein with 
Synthetic Substitute, Open Approach
Replacement of vessel-to-vessel cannula
031B0Z
F
3927
Bypass Right Radial Artery to Lower Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
031C0JF 3994
Bypass Left Radial Artery to Lower Arm Vein with Synthetic 
Substitute, Open Approach
Replacement of vessel-to-vessel cannula
031C0Z
F
3927
Bypass Left Radial Artery to Lower Arm Vein, Open 
Approach
Arteriovenostomy for renal dialysis
03LK0C
Z
3953
Occlusion of Right Internal Carotid Artery with Extraluminal 
Device, Open Approach
Repair of arteriovenous fistula
03LK0Z
Z
3953
Occlusion of Right Internal Carotid Artery, Open Approach
Repair of arteriovenous fistula
03LK3C
Z
3953
Occlusion of Right Internal Carotid Artery with Extraluminal 
Device, Percutaneous Approach
Repair of arteriovenous fistula
03LK3Z
Z
3953
Occlusion of Right Internal Carotid Artery, Percutaneous 
Approach
Repair of arteriovenous fistula
Appendix

03LK4C
Z
3953
Occlusion of Right Internal Carotid Artery with Extraluminal 
Device, Percutaneous Endoscopic Approach
Repair of arteriovenous fistula
03LK4Z
Z
3953
Occlusion of Right Internal Carotid Artery, Percutaneous 
Endoscopic Approach
Repair of arteriovenous fistula
03LL0C
Z
3953
Occlusion of Left Internal Carotid Artery with Extraluminal 
Device, Open Approach
Repair of arteriovenous fistula
03LL0Z
Z
3953
Occlusion of Left Internal Carotid Artery, Open Approach
Repair of arteriovenous fistula
03LL3C
Z
3953
Occlusion of Left Internal Carotid Artery with Extraluminal 
Device, Percutaneous Approach
Repair of arteriovenous fistula
03LL3Z
Z
3953
Occlusion of Left Internal Carotid Artery, Percutaneous 
Approach
Repair of arteriovenous fistula
03LL4C
Z
3953
Occlusion of Left Internal Carotid Artery with Extraluminal 
Device, Percutaneous Endoscopic Approach
Repair of arteriovenous fistula
03LL4Z
Z
3953
Occlusion of Left Internal Carotid Artery, Percutaneous 
Endoscopic Approach
Repair of arteriovenous fistula
03PY07
Z
3943
Removal of Autologous Tissue Substitute from Upper Artery, 
Open Approach
Removal of arteriovenous shunt for renal dialysis
03PY0J
Z
3994
Removal of Synthetic Substitute from Upper Artery, Open 
Approach
Replacement of vessel-to-vessel cannula
03PY0K
Z
3943
Removal of Nonautologous Tissue Substitute from Upper 
Artery, Open Approach
Removal of arteriovenous shunt for renal dialysis
03PY37
Z
3943
Removal of Autologous Tissue Substitute from Upper Artery, 
Percutaneous Approach
Removal of arteriovenous shunt for renal dialysis
03PY3J
Z
3994
Removal of Synthetic Substitute from Upper Artery, 
Percutaneous Approach
Replacement of vessel-to-vessel cannula
03PY3K
Z
3943
Removal of Nonautologous Tissue Substitute from Upper 
Artery, Percutaneous Approach
Removal of arteriovenous shunt for renal dialysis
03PY47
Z
3943
Removal of Autologous Tissue Substitute from Upper Artery, 
Percutaneous Endoscopic Approach
Removal of arteriovenous shunt for renal dialysis
03PY4J
Z
3994
Removal of Synthetic Substitute from Upper Artery, 
Percutaneous Endoscopic Approach
Replacement of vessel-to-vessel cannula
03PY4K
Z
3943
Removal of Nonautologous Tissue Substitute from Upper 
Artery, Percutaneous Endoscopic Approach
Removal of arteriovenous shunt for renal dialysis
03VK0C
Z
3953
Restriction of Right Internal Carotid Artery with Extraluminal 
Device, Open Approach
Repair of arteriovenous fistula
03VK3C
Z
3953
Restriction of Right Internal Carotid Artery with Extraluminal 
Device, Percutaneous Approach
Repair of arteriovenous fistula
03VK4C
Z
3953
Restriction of Right Internal Carotid Artery with Extraluminal 
Device, Percutaneous Endoscopic Approach
Repair of arteriovenous fistula
03VL0C
Z
3953
Restriction of Left Internal Carotid Artery with Extraluminal 
Device, Open Approach
Repair of arteriovenous fistula
03VL3C
Z
3953
Restriction of Left Internal Carotid Artery with Extraluminal 
Device, Percutaneous Approach
Repair of arteriovenous fistula
03VL4C
Z
3953
Restriction of Left Internal Carotid Artery with Extraluminal 
Device, Percutaneous Endoscopic Approach
Repair of arteriovenous fistula
03WY0J
Z
3994
Revision of Synthetic Substitute in Upper Artery, Open 
Approach
Replacement of vessel-to-vessel cannula
03WY3J
Z
3994
Revision of Synthetic Substitute in Upper Artery, 
Percutaneous Approach
Replacement of vessel-to-vessel cannula
03WY4J
Z
3994
Revision of Synthetic Substitute in Upper Artery, 
Percutaneous Endoscopic Approach
Replacement of vessel-to-vessel cannula
03WYX
JZ
3994
Revision of Synthetic Substitute in Upper Artery, External 
Approach
Replacement of vessel-to-vessel cannula
05HY33
Z
3895
Insertion of Infusion Device into Upper Vein, Percutaneous 
Approach
Venous catheterization for renal dialysis
06HY33
Z
3895
Insertion of Infusion Device into Lower Vein, Percutaneous 
Approach
Venous catheterization for renal dialysis
0TS00Z
Z
5561
Reposition Right Kidney, Open Approach
Renal autotransplantation
0TS10Z
Z
5561
Reposition Left Kidney, Open Approach
Renal autotransplantation
0TY00Z
0
5569
Transplantation of Right Kidney, Allogeneic, Open Approach Other kidney transplantation
0TY00Z
1
5569
Transplantation of Right Kidney, Syngeneic, Open Approach
Other kidney transplantation
Appendix

0TY00Z
2
5569
Transplantation of Right Kidney, Zooplastic, Open Approach
Other kidney transplantation
0TY10Z
0
5569
Transplantation of Left Kidney, Allogeneic, Open Approach
Other kidney transplantation
0TY10Z
1
5569
Transplantation of Left Kidney, Syngeneic, Open Approach
Other kidney transplantation
0TY10Z
2
5569
Transplantation of Left Kidney, Zooplastic, Open Approach
Other kidney transplantation
3E1M39
Z
5498
Irrigation of Peritoneal Cavity using Dialysate, Percutaneous 
Approach
Peritoneal dialysis
5A1D70
Z
3995
Performance of Urinary Filtration, Intermittent, Less than 6 
Hours Per Day
Hemodialysis
5A1D80
Z
3995
Performance of Urinary Filtration, Prolonged Intermittent, 6-
18 hours Per Day
Hemodialysis
5A1D90
Z
3995
Performance of Urinary Filtration, Continuous, Greater than 
18 hours Per Day
Hemodialysis
ICD10
ICD9 ICD10 Description
ICD9 Description
I0981
39891 Rheumatic heart failure
Rheumatic heart failure (congestive)
I110
40291 Hypertensive heart disease with heart failure
Unspecified hypertensive heart disease with heart failure
I130
40491 Hypertensive heart and chronic kidney disease with heart 
failure and stage 1 through stage 4 chronic kidney disease, or 
unspecified chronic kidney disease
Hypertensive heart and chronic kidney disease, unspecified, with heart failure and with 
chronic kidney disease stage I through stage IV, or unspecified
I132
40493 Hypertensive heart and chronic kidney disease with heart 
failure and with stage 5 chronic kidney disease, or end stage 
renal disease
Hypertensive heart and chronic kidney disease, unspecified, with heart failure and 
chronic kidney disease stage V or end stage renal disease
I501
4281
Left ventricular failure, unspecified
Left heart failure
I5020
4280
Unspecified systolic (congestive) heart failure
Congestive heart failure, unspecified
I5021
4280
Acute systolic (congestive) heart failure
Congestive heart failure, unspecified
I5022
4280
Chronic systolic (congestive) heart failure
Congestive heart failure, unspecified
I5023
4280
Acute on chronic systolic (congestive) heart failure
Congestive heart failure, unspecified
I5030
4280
Unspecified diastolic (congestive) heart failure
Congestive heart failure, unspecified
I5031
4280
Acute diastolic (congestive) heart failure
Congestive heart failure, unspecified
I5032
4280
Chronic diastolic (congestive) heart failure
Congestive heart failure, unspecified
I5033
4280
Acute on chronic diastolic (congestive) heart failure
Congestive heart failure, unspecified
I5040
4280
Unspecified combined systolic (congestive) and diastolic 
(congestive) heart failure
Congestive heart failure, unspecified
I5041
4280
Acute combined systolic (congestive) and diastolic 
(congestive) heart failure
Congestive heart failure, unspecified
I5042
4280
Chronic combined systolic (congestive) and diastolic 
(congestive) heart failure
Congestive heart failure, unspecified
I5043
4280
Acute on chronic combined systolic (congestive) and diastolic 
(congestive) heart failure
Congestive heart failure, unspecified
I50810
4289
Right heart failure, unspecified
Heart failure, unspecified
I50811
4289
Acute right heart failure
Heart failure, unspecified
I50812
4289
Chronic right heart failure
Heart failure, unspecified
I50813
4289
Acute on chronic right heart failure
Heart failure, unspecified
I50814
4280
Right heart failure due to left heart failure
Congestive heart failure, unspecified
I5082
4289
Biventricular heart failure
Heart failure, unspecified
I5083
4289
High output heart failure
Heart failure, unspecified
I5084
4289
End stage heart failure
Heart failure, unspecified
I5089
4289
Other heart failure
Heart failure, unspecified
I509
4289
Heart failure, unspecified
Heart failure, unspecified
ICD10
ICD9 ICD10 Description
ICD9 Description
I950
4581
Idiopathic hypotension
Chronic hypotension
I951
4580
Orthostatic hypotension
Orthostatic hypotension
I953
45821 Hypotension of hemodialysis
Hypotension of hemodialysis
I9589
4588
Other hypotension
Other specified hypotension
I959
4589
Hypotension, unspecified
Hypotension, unspecified
I952
45829 Hypotension due to drugs
Other iatrogenic hypotension
I9581
45829 Postprocedural hypotension
Other iatrogenic hypotension
ICD10
ICD9 ICD10 Description
ICD9 Description
E875
2767
Hyperkalemia
Hyperpotassemia
Hypotension Dx
Hyperkalemia Dx
Heart Failure Dx
Appendix