1. Angiotensin converting enzyme inhibitors / angiotensin receptor blockers and contrast induced nephropathy in patients receiving cardiac catheterization: results from the CAPTAIN trial

2. CAPTAIN trial: study design
A randomized study of holding angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus continuing ACEI/ARB prior to cardiac catheterization in patients with chronic kidney disease
Patients on ACEI/ARB and scheduled for cardiac cath ≥24hrs from enrolment with
chronic kidney disease (CKD)*
RANDOMIZED
Continue ACEI/ARB
Hold ACEI/ARB
Hold 24 hrs before and 96 hrs after procedure
All patients receive peri-procedural intravenous hydration and N-acetylcystine
Follow-up: between hours post-procedure
Primary Outcome: Acute kidney injury (AKI)**
Secondary Outcome: Rise in serum creatinine post procedure
*CKD: Cr >= 150umol/L within 3 months before cardiac catheterization and/or documented Cr >= 132umol/L within 1 week before cardiac catheterization
** AKI: absolute rise in serum creatinine of ≥ 44umol/L from baseline and/or a relative rise in serum creatinine of ≥ 25% compared with baseline measured at hours post cardiac catheterization 2 2

3. Selected baseline characteristics
Variable
CONTINUE
(N=102)
HOLD
(N=106)
P-value
Demographic characteristics
Age (mean, SD)
72.4 (8.4 )
73.2 (9.1 )
0.5600
Gender (% Female)
27 (26.5 )
28 (26.4 )
1.0000
Medical history (%)
Diabetes mellitus
57 (55.9 )
55 (51.9 )
0.5806
Hypertension
96 (94.1 )
93 (87.7 )
0.1488
Congestive heart failure
12 (11.8 )
17 (16.0 )
0.4266
Ejection fraction (median, %)
50.0 (42.0 ,55.0 )
50.0 (35.0 ,55.0 )
0.2023
Medications prior to cardiac catheterization (%)
Aspirin
80.4
77.4
0.6145
COX II inhibitors
1.0
0.4904
Other NSAIDS
5.9
2.8
0.3250
Loop diuretics
26.5
34.0
0.2910
Thiazide diuretics
17.6
14.2
0.5704
Beta Blockers
59.8
67.9
0.2494
Spironolactone
2.0
5.7
0.2802
Statins
78.4
75.5
0.6258
ACEI/ARB
100.0
0.9999
Baseline characteristics were well balanced between the two groups. Note, high rates of diabetes were noted which were similar in both groups although there was a trend towards higher rates of insulin used to treat diabetics in the continue ACEI/ARB group (24.5%. vs. 14.2%, p=0.08). All patients were on an ACEI/ARB (ACEI [72.1%] or ARB [27.9%]) prior to randomization

4. Catheterization characteristics
Pre-catheterization
During catheterization
Variable
CONTINUE
(N=102)
HOLD
(N=106)
P-value
Hydration
Intravenous hydration (%)
100
99.1
0.9888
Rate of IV hydration (cc/hr mean, SD)
264.1 (103.9 )
278.2 (113.5 )
0.3530
Duration of IV hydration (hrs, mean, SD)
1.5 (0.9 )
1.5
(1.0 )
0.8498
Laboratory tests
Hemoglobin (g/dL, mean)
36.2
(46.9 )
35.9 (48.4 )
0.9601
Highest creatinine documented in last 3 mo. (umol/L, mean, SD)
160.4
(37.8 )
158.1 (35.9 )
0.6446
Pre-procedural creatinine within 1 wk of cath (umol/L, mean, SD)
151.3
(34.6 )
148.3 (35.0 )
0.5458
Creatinine level on day of Cath (umol/L, mean, SD)
143.3
(36.8 )
140.1 (32.9 )
0.5265
Variable
CONTINUE
(N=102)
HOLD
(N=106) P-
value
Visipaque
30.4
36.8
0.3288
Omnipaque
69.6
63.2
Contrast during procedure
Contrast (mL, mean, SD)
122.9
(65.5 )
109.8 (67.0 )
0.1561
Hemodynamic measurements during procedure
Blood pressure (systolic, mmHg, mean, SD)
134.8
(25.4 )
140.7 (26.9 )
0.1068
Blood pressure (diastolic, mmHg, mean, SD)
64.6
(14.6 )
67.8 (15.8 )
0.1385
SBP <90 mmHg for at least 5 min during procedure (%) 3
(2.9 )
1 (0.3)
0.3619
Cardiac catheterization
Left ventricular end-diastolic pressure (mmHg, mean, SD)
10.3
(5.2 )
10.4 (5.6 )
0.8637
PCI performed (%)
22.6
0.2057
Pre-catheterization characteristics showed patients were well hydrated with intravenous normal saline on average 1.5 hours before the procedure which was similar in both groups. Serum creatinine levels were elevated in keeping with renal insufficiency but were similar in the two groups
During cardiac catheterization, similar volumes of radioactive contrast were used and invasive hemodynamics were comparable between both groups

5. Primary outcome Acute kidney injury HR 0.59; 95% CI 0.30-1.19; p=0.16
Incidence of AKI defined as an absolute rise in serum creatinine of ≥ 44umol/L from baseline and/or a relative rise in serum creatinine of ≥ 25% compared with baseline measured at hours post cardiac catheterization

6. Secondary outcome Other outcome Variable CONTINUE (N=102) HOLD (N=106)
Hazard Ratio
(95% CI)
P value
Composite outcome*
4(3.92)
0.11(0.01,2.96)
0.0561
Death
1(0.98)
0.32(0.01,7.79)
0.4904 MI . NA
CHF
Ischemic stroke
Dialysis
Re-hospitalization
3(2.94)
0.14(0.01,2.63)
0.1162
P=0.03
*Composite of death, myocardial infarction, ischemic stroke, congestive heart failure, re-hospitalization or need for dialysis 72 hours post-procedure

7. Prespecified sub-group analyses Exploratory analysis40
18.2
11.1
0.61[0.12,2.96]
159
18.4
10.8
0.59[0.27,1.28]
109
22.8
13.5
0.59[0.26,1.37] 90
12.2
8.2
0.67[0.19,2.33]
10.6
4.8
0.45[0.04,4.60] 74
19.4
7.0
0.36[0.10,1.33] 80
21.7
17.7
0.81[0.33,2.02]
208
10.9
0.59[0.30,1.19]
Age
<65Yr
>=65Yr
Diabetes
Yes No
Mehran risk
score
0-5
6-10
>10
Total
Event Rate (%)
Patient#
Continue
Hold
Risk Ratio (95% CI)
Favours Hold
Favours Continue
0.04
0.1 1 5 10 20
Modification of diet
in renal disease
formula
Cockcroft-gault
formula
P=0.06
P=0.06
There was no significant heterogeneity in the primary outcome of AKI in subgroups stratified according to age or diabetes
Reduction in renal function following cardiac catheterization seems to be attenuated with holding ACEI/ARB regardless of the measurement used for renal function.
Change in Renal Function Following Cardiac Catheterization

8. Conclusion
Our study showed that in patients with renal insufficiency requiring cardiac catheterization, holding ACEI/ARB did not differ from continuing ACEI/ARB in preventing acute kidney injury
However, holding ACEI/ARB resulted in:
Significantly lower rise in serum creatinine following coronary angiography
Attenuation in renal function decline following angiography
Improved clinical outcomes
Large scale clinical trial is warranted
However, we do believe a larger scale clinical trial is warranted to definitively address this issue.