Date post: | 17-Jan-2016 |
Category: |
Documents |
Upload: | shawn-powell |
View: | 220 times |
Download: | 0 times |
Determination of the RAdial versus GrOiN coronary
angioplasty
The Result of DRAGON Trial
Shigeru Saito, MDDepartment of Cardiology and Catheterization Laboratory
Shonan Kamakura General Hospital, Kamakura, Japan
on behalf of Dragon Trial investigators
Disclosure Statement of Financial Interest
• Grant/Research Support• Consulting Fees/Honoraria• Major Stock Shareholder/Equity• Royalty Income• Ownership/Founder• Intellectual Property Rights• Other Financial Benefit
• None• TERUMO, Boston Scientific• None• None• None• None• None
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Background this study
• TRI is getting more popular all around the world.
• However, it is not yet clear whether ad-hoc TRI strategy can provide clinical outcomes similar to TFI strategy.
• Thus, we initiated DRAGON trial to show the effectiveness of ad-hoc TRI strategy in the real world.
Objective of this study
• To determine the clinical benefit of the transradial approach compared to the transfemoral approach in patients, who receive percutaneous coronary intervention in the real world practice.
• The benefit is shown based on the non-inferiority of TRI in terms of clinical effectiveness at 1 year and on the superiority of TRI to reduce the major bleeding complications at 7 days compared to TFI.
Primary Investigators
Shigeru SAITO, MD Yong HUO, MD
Honorary Primary Investigator
Runlin GAO, MDFerdinard KIEMENEIJ, MD
Steering Committee Shigeru SAITO Junbo GE Yujie ZHOU Guosheng FU Jian’an WANGBo XU
Yong HUOShubin QIAOYaling HANJiyan CHENHaichang WANGWei LI
Biostatistic Analysis Medical Research & Biometrics CenterNational Center for Cardiovascular DiseasesCardiovascular Institute & Fuwai Hospital
Sponsor TERUMO
CRO/DM/CL CCRF
Study Organization
Endpoints
Primary Endpoint Major Adverse Cardiac or Cerebrovascular
Event (MACCE) free rate at 12 months
Major Secondary Endpoint Major bleeding complication (BARC definition
type 3 or 5) free rate at 7 days
Statistical considerations
• This study had 80% statistical powered to demonstrate the non-inferiority (NI margin=5%) of TRI on primary endpoint (MACCE-free rate at 1 year) comparing to TFI
• And also powered (>85%) to demonstrate the superiority of TRI on major secondary endpoint (bleeding-free rate at 7 days) comparing to TFI
• Intention-To-Treat (ITT) principle had been used for the primary analysis
Enrollments
Patients who had PCI were the target population
TRI(N=1,212)
TFI (N=527)
P-value
Male (%) 72.5% 64.7% 0.001
Age (yrs) 61.1±10.8 62.9±10.9 0.001
Height (cm) 168.6±6.9 166.9±7.5 <0.001
Weight (Kg) 71.2±10.6 69.0±10.8 <0.001
BMI (Kg/m2) 25.0±3.1 24.6±3.1 0.049
Heart Rate (Beats/m) 72.1±11.8 72.4±13.0 0.626
Current Smoker (%) 37.8% 31.3% 0.033
Baseline characteristics(PCI population before adjustment)
Disease history(PCI population before adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Hypertension (%) 58.7% 60.9% 0.380
Hyperlipidemia (%) 15.2% 11.8% 0.043
Diabetes (%) 25.0% 24.9% 0.950
Prior MI (%) 11.4% 13.7% 0.185
Prior PCI (%) 12.1% 14.2% 0.231
Prior CABG (%) 0.2% 3.2% <0.001
Cerebrovascular Disease (%) 11.0% 12.3% 0.415
Peripheral vascular Disease(%) 1.4% 0.9% 0.424
Family history of CAD (%) 8.8% 8.3% 0.744
Baseline diagnosis(PCI population before adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Silent Myocardial Ischemia (%) 1.7% 1.5% 0.746
Angina (%) 64.0% 55.6% 0.001
MI (%) 34.2% 42.9% 0.001
LVEF (%) 59.1±9.2 58.5±9.6 0.329
NYHA class (%)
Ⅰ 63.2% 56.9% 0.049
Ⅱ 33.3% 36.9%
Ⅲ 3.4% 6.3%
Ⅳ 0.2% 0.0%
Killip class (%)
Ⅰ 83.4% 78.3% 0.345
Ⅱ 12.6% 16.9%
Ⅲ 3.4% 3.4%
Ⅳ 0.6% 1.4%
Kaplan-Meier curveMACCE-free rate at 12 months
(PCI population before adjustment)
TRI 1212 1168 1147 1143 1133 1125 1114TFI 527 494 483 475 467 462 459
HR = 0.707 (95% CI: 0.443-1.129)P-value (log-rank test): 0.144
Pts. at risk
TRITFI
Primary EndpointMACCE-free rate at 12 months
The non-inferiority was met as the upper 95% confidence bound is less than the non-inferiority margin (5%)
Difference [95% CI]
TRI(N=1,212)
TFI(N=527)
Difference[95% CI]
TFI-TRI
P-value(non-
inferiority)
96.1% 94.4%-1.7%
[-4.0%; 0.6%]<0.001
TRI is better TFI is better
Non-inferiority
-5% 0% 5%
(PCI population before adjustment)
Major bleeding complication-free rate at 7 days (major 2nd endpoint)
There was no significant difference between the TRI and TFI group on the 2nd endpoint among the unadjusted observed data
Difference [95% CI]
TRI(N=1212)
TFI(N=527)
Difference[95% CI]
TFI-TRI
P-value(superiority)
99.8% 99.4%-0.4%
[-1.1%; 0.3%]0.131TRI is better TFI is better
-3% 0% 3%
(PCI population before adjustment)
• The 23 baseline covariates had been included in the PS model were pre-specified without any knowledge of clinical outcomes (both efficacy & safety)
• HL test had a P=0.857
• IPW (inverse probability
weighting) had been
carried out
Since we unexpectedly found imbalanced randomized allocation, we did propensity score analysis based on 23 baseline covariates.
TRI(N=1,212)
TFI (N=527)
P-value
Male (%) 70.4% 70.5% 0.928
Age (yrs) 61.54 ±12.85 61.15 ±20.62 0.467
Height (cm) 168.09 ±8.34 167.71 ±13.65 0.349
Weight (Kg) 70.74 ±12.82 70.39 ±21.40 0.573
BMI (Kg/m2) 24.99 ±3.78 24.97 ±5.83 0.926
Heart Rate (Beats/m) 72.12 ±13.97 72.65 ±24.25 0.378
Current Smoker (%) 37.1% 33.3% 0.012
Baseline characteristics(After IPW adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Hypertension (%) 59.0% 56.1% 0.084
Hyperlipidemia (%) 13.9% 13.1% 0.458
Diabetes (%) 25.4% 24.4% 0.492
Prior MI (%) 12.2% 11.1% 0.301
Prior PCI (%) 12.3% 13.4% 0.319
Prior CABG (%) 0.8% 1.1% 0.323
Cerebrovascular Disease (%) 10.7% 12.9% 0.039
Peripheral vascular Disease(%) 1.2% 1.2% 0.894
Family history of CAD (%) 7.9% 7.2% 0.482
Disease history(After IPW adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Silent Myocardial Ischemia (%)
1.7% 1.8% 0.797
Angina (%) 61.0% 62.7% 0.283
MI (%) 37.4% 35.5% 0.248
LVEF (%) 58.63 ±11.24 58.61 ±16.92 0.973
NYHA class (%)
Ⅰ 63.3% 64.5% 0.010
Ⅱ 33.0% 29.7%
Ⅲ 3.6% 5.8%
Ⅳ 0.2% 0.0%
Baseline diagnosis(After IPW adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Killip class (%)
Ⅰ 82.7% 76.8% 0.007
Ⅱ 13.4% 18.2%
Ⅲ 3.5% 2.9%
Ⅳ 0.4% 2.0%
Baseline diagnosis (cont.)(After IPW adjustment)
TRI(N=1,212)
TFI (N=527)
P-value
Lesion number 1.3±0.7 1.4±1.2 0.054
Procedural success (%) 99.6% 98.7% 0.007
Operative complication (%) 1.6% 3.3% 0.001
Procedure time (min) 59.1±35.3 60.1±62.3 0.516
Procedural information (After IPW adjustment)
TRI (N=1,611)
TFI(N=729)
P-value
TYPE (%)
A 1.8% 2.0% 0.939
B1 25.2% 25.6%
B2 7.7% 7.4%
C 65.3% 65.0%
Bifurcation lesion (%) 9.4% 9.6% 0.864
CTO (%) 6.1% 6.3% 0.754
Pre-op TIMI 0&1 (%) 23.9% 30.9%
Number of stents/lesion
1.2±0.7 1.2±1.1 0.515
Lesion characteristics (PCI population before adjustment)
HR = 0.928 (95% CI: 0.672-1.280)P-value (log-rank test): 0.822
Kaplan-Meier curveMACCE-free rate at 12 months
(After IPW adjustment)
TRI 1212 1168 1147 1143 1133 1125 1114TFI 527 494 483 475 467 462 459
Pts. at risk
TRITFI
Difference [95% CI]
TRI is better TFI is better
Non-inferiority
-5% 0% 5%
TRI(N=1,212)
TFI(N=527)
Difference[95% CI]
TFI-TRI
P-value(non-
inferiority)
95.8% 95.5%-0.3%
[-1.7%; 1.0%]<0.001
Primary EndpointMACCE-free rate at 12 months
(After IPW adjustment)
The non-inferiority was met as the upper 95% confidence bound is less than the non-inferiority margin (5%)
The superiority is met (after propensity score-IPW adjustment) as the upper 95% confidence bound is less than 0%
Difference [95% CI]
TRI(N=1212)
TFI(N=527)
Difference[95% CI]
TFI-TRI
P-value(superiority)
99.9% 99.0%-0.9%
[-1.4%; -0.4%]<0.001
TRI is better TFI is better
-3% 0% 3%
Major bleeding complication-free rate at 7 days (major 2nd endpoint)
(After IPW adjustment)
Limitation
• Since randomization between TRI and
TFI was made before assessing the
feasibility of CABG or medical therapy,
there might be some bias favoring for
TFI.
Conclusion
• In real world PCI situation with ad-hoc
PCI strategy, TRI is as effective as TFI
in terms of 12 months’ MACCE, and TRI
brings less incidence of bleeding
complications at 1 week after PCI.