A comparison of the RE-LY and Rocket AF Trials
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Media:ROCKET_vs_RELY_comparison.ppt
Comparison of RE-LY and Rocket AF Trials
Trial Design
- Both had non-inferiority to warfarin as primary endpoint
- Rocket AF required 2 risk factors for entry, RE-LY 1 risk factor
- Both randomized trials
- Rocket AF administered warfarin in a blinded fashion, RE-LY did not
- There was a dose adjustment for impaired CrCl in Rocket AF
- INR target range 2-3 in both
Statistical Methods
RELY: Primary Efficacy Evaluation: Stroke or non-CNS Embolism
Non-Inferiority: Intention-to-treat
Superiority: Intention-to-treat
Rocket AF: Primary Efficacy Evaluation: Stroke or non-CNS Embolism
Non-Inferiority: Protocol Compliant on treatment
Superiority: On Treatment and then by Intention-to-Treat
Trial Execution
| Re-LY | Rocket AF | |
|---|---|---|
| Countries | 44 | 45 |
| Patients | 18,113 | 14,264 |
| Median Duration of Follow-Up | 2 years (about 730 days) | 589 days of exposure, 707 days with follow-up |
| Time in Therapeutic Range (TTR) | 64% | 57.8% |
Statistical Methods
RELY: Primary Safety Evaluation: Major Bleeding
Rocket AF: Primary Safety Evaluation: Major or non-Major Clinically Relevant Bleeding
Rates of Drug Discontinuation
| RE-LY | |
|---|---|
| 1 Year: | |
| Dabigatran 110 mg: | 14.5% |
| Dabigatran 150 mg: | 15.5% |
| Warfarin: | 10.2% |
| 2 Years: | |
| Dabigatran 110 mg: | 20.7% |
| Dabigatran 150 mg: | 21.2% |
| Warfarin: | 16.6% |
| Rocket AF | |
| Rivaroxaban: | 23.9% |
| Warfarin: | 22.4% |
RE-LY: Baseline Characteristics
| Characteristics | Dabigatran 110 mg | Dabigatran 150 mg | Warfarin |
|---|---|---|---|
| Randomized | 6015 | 6076 | 6022 |
| Mean age (years) | 71.4 | 71.5 | 71.6 |
| Male (%) | 64.3 | 63.2 | 63.3 |
| CHADS2 score | 2.1 | 2.2 | 2.1 |
| (mean) | |||
| 0-1 (%) | 32.6 | 32.2 | 30.9 |
| 2 (%) | 34.7 | 35.2 | 37.0 |
| 3+ (%) | 32.7 | 32.6 | 32.1 |
| Prior stroke/TIA (%) | 19.9 | 20.3 | 19.8 |
| Prior MI (%) | 16.8 | 16.9 | 16.1 |
| CHF (%) | 32.2 | 31.8 | 31.9 |
| Baseline ASA (%) | 40.0 | 38.7 | 40.6 |
| Warfarin Naïve (%) | 49.9 | 49.8 | 51.4 |
Rocket AF: Baseline Demographics
| Rivaroxaban (N=7081) | Warfarin (N=7090) | |
|---|---|---|
| CHADS2 Score (mean) | 3.48 | 3.46 |
| 2 (%) | 13 | 13 |
| 3 (%) | 43 | 44 |
| 4 (%) | 29 | 28 |
| 5 (%) | 13 | 12 |
| 6 (%) | 2 | 2 |
| Prior VKA Use (%) | 62 | 63 |
| Congestive Heart Failure (%) | 63 | 62 |
| Hypertension (%) | 90 | 91 |
| Diabetes Mellitus (%) | 40 | 39 |
| Prior Stroke/TIA/Embollism (%) | 55 | 55 |
| Prior Myocardial Infarction (%) | 17 | 18 |
Rocket AF was a Higher Risk Patient Population
- Whereas 32.4% of patients in RE-LY were low risk CHADS 0-1, there were none of these patients in Rocket AF
- Whereas just over 32% of patients in RE-LY were high risk CHADS score of 3 or more, over 85% of Rocket AF patients had a CHADS score of 3 or more
- RE-LY patients were about 71.5 years old, and Rocket AF patients were 73 years old
- Prior stroke TIA embolism was about 20% in RE-LY and was 55% in Rocket AF
- About half of RE-LY patients were warfarin naïve, whereas 37.5% of Rocket AF patients were warfarin naïve
Primary Endpoint of Stroke or Systemic Embolism
| Rely | ||
|---|---|---|
| Dabigatran 110 mg | 1.53% per year | p=0.34 |
| Dabigatran 150 mg | 1.11% per year | p<0.001 |
| Warfarin | 1.69% per year | |
| Rocket AF | ||
| Rivaroxaban 20 mg | 2.12% per year | p=0.117 |
| Warfarin | 2.42% |
Hemorrhagic Stroke
| Rely | HR | p-value | |
|---|---|---|---|
| Dabigatran 110 mg | 0.12% / yr | 0.31 | <0.001 |
| Dabigatran 150 mg | 0.10% / yr | 0.26 | <0.001 |
| Warfarin | 0.38% / yr | ||
| Rocket AF | |||
| Rivaroxaban 20 mg | 0.26 / year | 0.59 | 0.024 |
| Warfarin | 0.44 / yr |
Ischemic Stroke
| Rely | HR | p-value | |
|---|---|---|---|
| Dabigatran 110 mg | 1.34% / yr | 1.20 | 0.35 |
| Dabigatran 150 mg | 0.92% / yr | 0.76 | 0.03 |
| Warfarin | 1.20% / yr | ||
| Rocket AF | |||
| Rivaroxaban 20 mg | 1.34 / year | 0.94 | 0.58 |
| Warfarin | 1.42 / yr |
Stroke Conclusions
- Both Dabigatran and Rivaroxaban reduced hemorrhagic stroke
- The reduction in hemorrhagic stroke was relatively greater (numerically) for Dabigatran
- Both drugs were therefore safer
- Only Dabigatran, however, was associated with a reduction in ischemic stroke. Rivaroxaban was not.
Conclusions: RE-LY vs Rocket AF
- Both drugs were non-inferior to Warfarin in reducing stroke and systemic embolism
- In an Intent-to-Treat analysis, 150 mg of dabigatran was superior to warfarin while rivaroxaban was not
- Dabigatran 150 mg reduced the risk of hemorrhagic stroke (HR 0.26, p<0.001) as did rivaroxaban (HR 0.59, p=0.024) (both were safe). There was less fatal bleeding with rivaroxaban, but numerically more major bleeding with rivaroxaban.
- Dabigatran 150 mg also reduced the risk of ischemic stroke (HR=0.76, p=0.03) while rivaroxaban did not (p=0.58)(dabigatran was associated with efficacy)
- In the intent-to-treat analysis, there was a strong trend for a mortality reduction with dabigatran 150 mg (p=0.051) while there was a modest trend for mortality improvement for rivaroxaban (4.52 / yr vs 4.91 / yr, p=0.152)