2.1

Study design and randomization

The study was designed as single center, parallel group, open-label, randomized clinical trial. Patients over 18 years old undergoing diagnostic TRA with appropriate clinical indication were prospectively enrolled. Exclusion criteria were 1) patients with acute coronary syndromes or requiring emergency intervention, 2) patients with low blood pressure (systolic blood pressure < 100 mmHg) and/or bradycardia (heart rate < 50 beat per minute) before procedure and 3) patients unwilling to participate. All patients participating in the study gave written informed consent. The study was approved by Ethics Committee on Human Research, Faculty of Medicine, Kocaeli University, Turkey.

2.2

TRA procedure

Eligible patients were allocated to short-acting SL and IA nitroglycerin groups by computer-generated random numbers before the procedure. SL nitroglycerin was administered prior to RA puncture in commercially available spray form which contains 400-mcg nitroglycerin per application. RA puncture was attempted between 3 to 5 minutes of SL nitroglycerin administration. If more than one attempt was necessary and puncture was not completed within 2 minutes, additional SL nitroglycerin was administered at the discretion of the operator. IA nitroglycerin was administered through the arterial sheath at the dose of 200 mcg.

Right RA was used as the first choice throughout the study. Left RA was used in patients with negative modified Allen’s test or previous coronary artery bypass graft operation or previous TRA from right RA. Verapamil was not included in spasmolytic cocktail. After subcutaneous injection of prilocaine, arterial puncture was made by using 21G needle with 0,018 guidewire. An 11 cm 6 F hydrophilic-coated sheath was introduced into RA. Diagnostic angiography was performed using 5 F standard diagnostic catheters. Brachiocephalic tortuosity was defined as clinically important tortuosity or anatomic variation of upper limb arteries making catheter manipulation difficult. Fixed-dose unfractionated heparin (5000 IU) was administered through the diagnostic catheter into the ascending aorta. Number of angiographic views necessary for satisfactory reporting was left to the operator. If additional nitroglycerin was required during procedure for clinically severe spasm, the operator was allowed to give nitroglycerin through the diagnostic catheter. Ad-hoc percutaneous coronary intervention for a suitable lesion was not allowed in study participants. After sheath removal, hemostasis was achieved with gauze and compression for 4 hours (gradual release of compression pressure after 2 hours) without use of any special equipment (inflatable wristband, etc). All TRAs were undertaken by single interventional cardiologist who performs more than 500 transradial procedures per year and who use RA as default arterial access site for coronary procedures.

2.3

Outcome measures

Primary endpoints of the study were puncture time and number of puncture attempts. Puncture time was measured from the onset of puncture to sheath placement. Multiple puncture was defined as the need for more than one puncture attempt to cannulate artery. Secondary endpoint was the incidence of RAS. RAS was defined as marked forearm pain plus resistance to catheter manipulation or sheath withdrawal reported by the operator. Routine arteriography to confirm RAS was not performed, as it could provoke pain or discomfort to asymptomatic patient.

Procedure time was measured from the onset of puncture to securing hemostasis after sheath removal. Other recorded parameters were development of hypotension and/or bradycardia related to nitroglycerin administration (arterial blood pressure dipping below 90 mmHg and/or heart rate dipping below 50 beat per minute with accompanying symptoms), access site crossover and the incidence of radial artery occlusion (RAO). RAO was evaluated at 1 week follow-up with Doppler ultrasonography. In addition, a composite endpoint of all adverse events related to TRA (incidence of multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and RAO) was calculated to compare two nitroglycerin routes.

2.4

Statistical analysis

Based on our daily practice, we expected a mean puncture time around 90 seconds (estimated standard deviation around 45 seconds) with IA nitroglycerin. Considering 20% reduction in puncture time as clinically significant, we estimated that 50 participants in each nitroglycerin group were needed to detect statistically significant difference with 0.80 power and 0.05 type I error. Mean of 1.5 puncture attempts were expected in IA nitroglycerin group based on the study of Ouadhour et al. Forty nine patients in each nitroglycerin group were needed to detect 40% reduction in puncture attempts (that means 1.3 puncture attempts or less), again with 0.80 power and 0.05 type I error. Therefore we decided to include 50 participants in each group.

Continuous data that showed symmetrical distribution were presented as means ± standard deviations and compared with student t-test. Data that did not distribute symmetrically were presented as medians (interquartile ranges) and compared with Mann–Whitney U test. Categorical variables were presented as numbers (percentages) and compared with chi square or Fisher’s exact test. Two-sided p value < 0.05 was considered significant. Data collection and analysis were performed using Statistical Package for the Social Sciences, version 11.0 (SPSS Inc., Chicago, IL).

2.1

Study design and randomization

The study was designed as single center, parallel group, open-label, randomized clinical trial. Patients over 18 years old undergoing diagnostic TRA with appropriate clinical indication were prospectively enrolled. Exclusion criteria were 1) patients with acute coronary syndromes or requiring emergency intervention, 2) patients with low blood pressure (systolic blood pressure < 100 mmHg) and/or bradycardia (heart rate < 50 beat per minute) before procedure and 3) patients unwilling to participate. All patients participating in the study gave written informed consent. The study was approved by Ethics Committee on Human Research, Faculty of Medicine, Kocaeli University, Turkey.

2.2

TRA procedure

Eligible patients were allocated to short-acting SL and IA nitroglycerin groups by computer-generated random numbers before the procedure. SL nitroglycerin was administered prior to RA puncture in commercially available spray form which contains 400-mcg nitroglycerin per application. RA puncture was attempted between 3 to 5 minutes of SL nitroglycerin administration. If more than one attempt was necessary and puncture was not completed within 2 minutes, additional SL nitroglycerin was administered at the discretion of the operator. IA nitroglycerin was administered through the arterial sheath at the dose of 200 mcg.

Right RA was used as the first choice throughout the study. Left RA was used in patients with negative modified Allen’s test or previous coronary artery bypass graft operation or previous TRA from right RA. Verapamil was not included in spasmolytic cocktail. After subcutaneous injection of prilocaine, arterial puncture was made by using 21G needle with 0,018 guidewire. An 11 cm 6 F hydrophilic-coated sheath was introduced into RA. Diagnostic angiography was performed using 5 F standard diagnostic catheters. Brachiocephalic tortuosity was defined as clinically important tortuosity or anatomic variation of upper limb arteries making catheter manipulation difficult. Fixed-dose unfractionated heparin (5000 IU) was administered through the diagnostic catheter into the ascending aorta. Number of angiographic views necessary for satisfactory reporting was left to the operator. If additional nitroglycerin was required during procedure for clinically severe spasm, the operator was allowed to give nitroglycerin through the diagnostic catheter. Ad-hoc percutaneous coronary intervention for a suitable lesion was not allowed in study participants. After sheath removal, hemostasis was achieved with gauze and compression for 4 hours (gradual release of compression pressure after 2 hours) without use of any special equipment (inflatable wristband, etc). All TRAs were undertaken by single interventional cardiologist who performs more than 500 transradial procedures per year and who use RA as default arterial access site for coronary procedures.

2.3

Outcome measures

Primary endpoints of the study were puncture time and number of puncture attempts. Puncture time was measured from the onset of puncture to sheath placement. Multiple puncture was defined as the need for more than one puncture attempt to cannulate artery. Secondary endpoint was the incidence of RAS. RAS was defined as marked forearm pain plus resistance to catheter manipulation or sheath withdrawal reported by the operator. Routine arteriography to confirm RAS was not performed, as it could provoke pain or discomfort to asymptomatic patient.

Procedure time was measured from the onset of puncture to securing hemostasis after sheath removal. Other recorded parameters were development of hypotension and/or bradycardia related to nitroglycerin administration (arterial blood pressure dipping below 90 mmHg and/or heart rate dipping below 50 beat per minute with accompanying symptoms), access site crossover and the incidence of radial artery occlusion (RAO). RAO was evaluated at 1 week follow-up with Doppler ultrasonography. In addition, a composite endpoint of all adverse events related to TRA (incidence of multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and RAO) was calculated to compare two nitroglycerin routes.

2.4

Statistical analysis

Based on our daily practice, we expected a mean puncture time around 90 seconds (estimated standard deviation around 45 seconds) with IA nitroglycerin. Considering 20% reduction in puncture time as clinically significant, we estimated that 50 participants in each nitroglycerin group were needed to detect statistically significant difference with 0.80 power and 0.05 type I error. Mean of 1.5 puncture attempts were expected in IA nitroglycerin group based on the study of Ouadhour et al. Forty nine patients in each nitroglycerin group were needed to detect 40% reduction in puncture attempts (that means 1.3 puncture attempts or less), again with 0.80 power and 0.05 type I error. Therefore we decided to include 50 participants in each group.

Continuous data that showed symmetrical distribution were presented as means ± standard deviations and compared with student t-test. Data that did not distribute symmetrically were presented as medians (interquartile ranges) and compared with Mann–Whitney U test. Categorical variables were presented as numbers (percentages) and compared with chi square or Fisher’s exact test. Two-sided p value < 0.05 was considered significant. Data collection and analysis were performed using Statistical Package for the Social Sciences, version 11.0 (SPSS Inc., Chicago, IL).