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.