Post-Procedural/Pre-Hemostasis Intra-Arterial Nitroglycerin: A Prospective, Randomized Trial Evaluating Intra-Sheath Nitroglycerin to Improve Arterial Patency After Transradial Catheterization

1. Post-Procedural/Pre-Hemostasis
Intra-Arterial Nitroglycerin:
A Prospective, Randomized Trial
Evaluating Intra-Sheath
Nitroglycerin to Improve Arterial
Patency After Transradial
Catheterization
(ClinicalTrials.gov Identifier: NCT02105493)
Surya Dharma*, MD, PhD, Sasko Kedev, MD, PhD, Tejas
Patel, MD, Ferdinand Kiemeneij, MD, PhD, Ian Gilchrist, MD
*Department of Cardiology and Vascular Medicine
Faculty of Medicine, University of Indonesia
National Cardiovascular Center Harapan Kita
Jakarta, Indonesia

2. Disclosure Statement of Financial Interest
I, Surya Dharma, MD, PhD DO NOT have a
financial interest/arrangement or
affiliation with one or more organizations
that could be perceived as a real or
apparent conflict of interest in the
context of the subject of this
presentation.

3. Introduction
• Despite trans-radial access (TRA) increasing
acceptance, radial artery occlusion (RAO)
continues to be one of the limitations of TRA
and potentially limits the radial artery as an
access site in the future.
• Currently, there is no data whether vasoactive
pharmacological therapy such as
nitroglycerin administered intra-arterially at
the end of the procedure may reduce the
incidence of RAO.

4. Main objective
• To evaluate whether administration of
nitroglycerin at the end of a trans-radial
procedure may preserve the patency of the
radial artery.
• Hypothesis: The addition of nitroglycerin
(nitric oxide donor) at the end of a TRA
procedure may preserve the patency of the
radial artery, thereby reduce the incidence of
RAO.

5. All patients undergoing trans-radial catheterization (N=1762)
Cocktail Administration
Catheterization procedure :
PCI, N =707
Coronary Angiography, N =1047
Others, N =8
Post procedure
56 pts were excluded due to:
-Hemodynamic Instability (25 pts)
-Nitrates intolerance (18 pts)
-Refuse to participate (13 pts)
Figure 1. Flow Chart of The Study
Randomization
Study design:
Multi-center, prospective,
randomized, placebo-
controlled trial involving three
experienced radial centers in
Indonesia, India, and
Macedonia
Each of the centers has
extensive experience in trans-
radial procedures (>80% TRA)

6. 500 µg NTG intra sheath
N =853
Placebo (saline) intra sheath
N =853
Post Administration
Hemostasis Compression
One day
Duplex ultrasonography of the arm:
Anterograde flow of the radial artery
Randomization
Figure 1. Flow Chart of The Study
Primary outcome:
The incidence of RAO
as confirmed by
absence of antegrade
flow at one day after
the trans-radial
procedure evaluated by
duplex ultrasound of
the radial artery

7. Figure 2. Sheath position (A) and Doppler
evaluation (B)

8. Results
Table 1. Baseline clinical characteristics.
Variables
All patients
n = 1706
Nitroglycerin
group
n = 853
Placebo
group
n = 853
P
Value
Age, years 59.27±10.37 59.15±10.53 59.38±10.23 0.654
Male gender, N (%) 1167 (68%) 589 (69%) 578 (68%) 0.567
Height, cm 168 (136-198) 167.81 ± 9.18 167.50±9.19 0.485
Weight, kg 75 (39-145) 75 (39-135) 74 (44-145) 0.737
Body Mass Index, kg/m2
26 (15-30) 26 (15-45) 26 (16-50) 0.685
Diabetes mellitus, N (%) 413 (24%) 212 (25%) 201 (23%) 0.534
Acute Coronary Syndrome, N (%) 486 (28%) 241 (28%) 245 (29%) 0.830
Glycoprotein IIb/IIIa inhibitor use, N (%) 3 (0.2%) 1 (0.1%) 2 (0.2%) 1.000
Procedure, N (%)
Coronary angiography 1025 (60%) 515 (60%) 510 (59%)
0.582PCI 677 (39%) 337 (39%) 340 (39%)
Others 4 (0.2%) 1 (0.1%) 3 (0.3%)
Continuos data are presented as mean ± standard deviation or median (minimum – maximum ).
PCI=percutaneous coronary intervention.

9. Table 2. Procedural Characteristics.
Variables
All patients
n = 1706
Nitroglycerin
group
n = 853
Placebo
group
n = 853
P
Value
Right radial artery access, N(%) 1684 (98%) 840 (98%) 844 (99%) 0.391
First radial procedure, N (%) 1375 (81%) 685 (80%) 690 (81%) 0.760
Repeated radial access, N (%) 331 (19%) 168 (20%) 163 (19%) 0.760
Radial puncture attempt, N(%)
Single puncture 1499 (88%) 750 (88%) 749 (88%) 0.941
Puncture technique, N (%)
Counter-puncture 548 (32%) 299 (35%) 249 (29%) 0.01
Sheath size, N (%)
5F 496 (29%) 257 (30%) 239 (28%) 0.337
6F 1207 (71%) 595 (70%) 612 (72%) 0.311
7F 2 (0.1%) 0 2 (0.2%) 0.500
8F 1 (0.05%) 1 (0.1%) 0 1.000
Heparin dose, IU 5000 (2500-
17,000)
5000 (2500-
17,000)
5000 (5000-
15,000)
0.613
Spasmolytic cocktails, N (%)
200 µg nitroglycerin 513 (30%) 278 (32%) 235 (27%) 0.023
300 µg nitroglycerin 175 (10%) 87 (10%) 88 (10%) 0.936

10. Table 2. Procedural Characteristics.
Variables
All patients
n = 1706
Nitroglycerin
group
n = 853
Placebo
group
n = 853
P
Value
5 mg verapamil 1018 (60%) 488 (57%) 530 (62%) 0.038
Route of heparin administration, N (%)
Intravenous 1547 (91%) 777 (91%) 770 (90%) 0.560
Procedural Time, minute 20 (1-240) 20 (1-120) 20 (1-240) 0.095
Hemostasis device, N (%)
TR-Band 1309 (77%) 670 (78%) 639 (75%) 0.075
Duration of hemostasis, hours 6.31 ± 5.72 6.72 ± 6.28 5.89 ± 5.08 0.160
Duration of hemostasis, N (%)
≤ 4 h 1153 (68%) 568 (66%) 585 (68%)
0.379
> 4 h 553 (32%) 285 (33%) 268 (31%)
Severe RAS, N (%) 13 (0.8%) 5 (0.8%) 8 (0.9%) 0.404
Residual arm pain pre-discharge, N (%) 76 (4.5%) 40 (4.7%) 36 (4.2%) 0.639
Hematoma EASY score >3, N (%) 0 0 0 NS
Symptom of hand ischemia, N (%) 0 0 0 NS
Continous data are presented as median (minimum – maximum) or mean ± standard deviation. F= french, IU=
international unit, RAS= radial artery spasm.

11. Table 3. Study outcome evaluated by doppler
ultrasound of the arteries at one day after the
trans-radial catheterization.
Variables
All patients
n = 1706
Nitroglycerin
group
n = 853
Placebo
group
n = 853
P
Value
Presence of RAO, N (%) 170 (9.9%) 70 (8.3%) 100 (11.7%) 0.015
Radial artery diameter, mm 2.78 ± 0.55 2.8 ± 0.52 2.77 ± 0.58 0.217
Ulnar artery diameter, mm 2.40 ± 0.42 2.41 ± 0.40 2.40 ± 0.43 0.732
RAO= radial artery occlusion.

12. Figure 3. Primary Outcome of The Study.
100/853100/853
0
3
6
9
12
8.3 %
11.7 %
p= 0.015
IncidenceofRAO
70/853
Nitroglycerin group Placebo group

13. Figure 4. Multivariate predictors of RAO.
OR= odds ratio, CI= confidence interval.
Several radial artery spasm
Procedural time > 60 minutes
Use of > 6F sheath
Counter puncture technique
Repeated radial access
Hemostatic compression >4h
Multiple puncture attempt
Body Mass Index > 25kg/m2
Diabetes Mellitus
Male gender
Age > 65 years
Use of nitroglycerin
0 1 2 3 4 5 6 87
OR = 0.62; 95% CI 0.44 – 0.87, p = 0.006
OR = 1.15; 95% CI 0.79 – 1.70, p = 0.463
OR = 0.99; 95% CI 0.68 – 1.43, p = 0.958
OR = 1.12; 95% CI 0.78 – 1.62, p = 0.532
OR = 0.82; 95% CI 0.57 – 1.13, p = 0.208
OR = 0.90; 95% CI 0.52 – 1.55, p = 0.710
OR = 3.11; 95% CI 1.66 – 5.82, p < 0.001
OR = 1.22; 95% CI 0.81 – 1.85, p = 0.331
OR = 1.65; 95% CI 0.89 – 3.08, p = 0.109
OR = 1.07; 95% CI 0.69 – 1.64, p = 0.758
OR = 0.69; 95% CI 0.24 – 1.99, p = 0.495
OR = 2.38; 95% CI 0.69 – 8.24, p = 0.170

14. Discussion
• A mechanism where by nitroglycerin (nitrous oxide donor)
may reduce the rate of RAO, is thought to be through its
vasodilatory effect of nitrous oxide.
• The dose of 500 µg nitroglycerin would have achieved a
maximal vasodilatory effect and expected to decrease the
intimal inflammation and intimal hyperplasia of the radial
artery.
• It is hypothesized that 500 µg of nitroglycerin would make a
vasodilation dominancy (through nitrous oxide) in the
endothelium of the radial artery that would
pharmacologically enhance flow, supporting a higher level
of patency to preserve the radial artery during a hemostasis
compression.

15. • RAO as detected by ultrasound in this study was
9.9%. Other studies reported the incidence of
RAO varying from 1.1% to 38%. The present study
suggests that in the real world setting, the
incidence of RAO is higher than expected.
• The strong predictor for the development of RAO
showed from this study was the duration of
hemostasis (OR= 3.11).
• The consistent results with respect to the
duration of hemostasis compression give an
insight that earlier decompression has to be
implemented in our daily practice of TRA.

16. Best radial practice for hemostasis
• Early hemostasis: <4h
• Patent hemostasis:
- Post-procedural nitroglycerin
- Ulnar compression during hemostasis

17. Study Limitation
• Due to the differences in hemostasis local
protocols and devices used, it was quite difficult
to apply a true patent hemostasis technique in all
patients.
• We did not perform a dose-ranging study nor
compare with other potentially more powerful
vasodilator agents.

18. • The administration of nitroglycerin through the
sheath at the end of a trans-radial catheterization
is associated with a reduced incidence of RAO,
one day after trans-radial procedures.
• This suggests that further evaluation of post-
procedural / pre-hemostasis pharmacologic
regimens may be an important aspect of
minimizing the risks of RAO after radial
procedures.
Conclusion

19. • Dharma S, Kedev S, Patel T, Rao SV, Bertrand O, Gilchrist
IC. Radial artery diameter does not correlate with body mass
index: a duplex ultrasound analysis of 1706 patients
undergoing trans-radial catheterization at three experienced
radial centers. (Int J Cardiol 2017;228:169-172)
• Dharma S, Kedev S, Patel T, Sukmawan R, Gilchrist IC, Rao
SV. Post-procedural/pre-hemostasis intra-arterial
nitroglycerin after transradial catheterization: A gender
based analysis. (Cardiovasc Revasc Med 2016;17:10-14)
• Dharma S, Kedev S, Patel T, Kiemeneij F, Gilchrist I. A Novel
approach to reduce radial artery occlusion after transradial
catheterization:Postprocedural/Prehemostasis Intraarterial
Nitroglycerin. (Cathet Cardiovasc Interv 2015;85:818-825)