ure to a VKA. Thirty-two percent of the population had never been exposed to a VKA. Concomitant diseases of patients in this trial included hypertension 79%, diabetes 23%, and CAD 28%. At baseline, 40% of patients were on aspirin and 6% were on clopidogrel. For patients randomized to warfarin, the mean percentage of time in therapeutic range (INR 2 to 3) was 64%; the mean percentages of time INR measurements were greater than 4 or less than 1.5 were 2% and 5%, respectively.
Relative to warfarin and to PRADAXA 110 mg twice daily, PRADAXA 150 mg twice daily significantly reduced the primary composite endpoint of stroke and systemic embolism (see Table 4 and Figure 1).
Table 4First Occurrence of Stroke or Systemic Embolism in the RE-LY Study PRADAXA
150 mg twice daily PRADAXA
110 mg twice daily Warfarin
Patients randomized 6076 6015 6022
Patients (%) with events 134 (2.2%) 183 (3%) 202 (3.4%)
Hazard ratio vs. warfarin (95% CI) 0.65 (0.52, 0.81) 0.90 (0.74, 1.10)
P-value for superiority 0.0001 0.3
Hazard ratio vs. PRADAXA 110 mg (95% CI) 0.72 (0.58, 0.90)
P-value for superiority 0.004
Figure 1 Kaplan-Meier Curve Estimate of Time to First Stroke or Systemic Embolism
The contributions of the components of the composite endpoint, including stroke by subtype, are shown in Table 5. The treatment effect was primarily a reduction in stroke. PRADAXA 150 mg twice daily significantly reduced both ischemic and hemorrhagic strokes relative to warfarin.
Table 5Strokes and Systemic Embolism in the RE-LY Study PRADAXA
150 mg twice daily Warfarin Hazard ratio vs. warfarin
(95% CI)
Patients randomized 6076 6022
Stroke 122 186 0.64 (0.51, 0.81)
Ischemic stroke 103 134 0.75 (0.58, 0.97)
Hemorrhagic stroke 12 45 0.26 (0.14, 0.49)
Systemic embolism 13 21 0.61 (0.30, 1.21)
The efficacy of PRADAXA 150 mg twice daily was generally consistent across major subgroups (see Figure 2).
Figure 2 Stroke and Systemic Embolism Hazard Ratios by Baseline Characteristics
Centers were ranked post hoc by the percentage of time that warfarin-treated patients were in therapeutic range (INR 2 to 3). Findings for stroke/systemic embolism, all-cause mortality, and major bleeds are shown for centers above and below the median level of INR control in Table 6. The benefits of PRADAXA 150 mg relative to warfarin were most apparent in patients enrolled at centers with INR control below the median.
Table 6Center INR Control in the RE-LY Study Centers with INR control
below the median of 67% Centers with INR control
above the median of 67%
Stroke/systemic embolism 0.57 (0.42, 0.76) 0.76 (0.55, 1.05)
All-cause mortality 0.78 (0.66, 0.93) 1.01 (0.84, 1.23)
Major bleed 0.82 (0.68, 0.99) 1.08 (0.89, 1.31)
The risk of myocardial infarction was numerically greater in patients who received PRADAXA (1.5% for 150 mg dose) than in those who received warfarin (1.1%).
16 HOW SUPPLIED/STORAGE AND HANDLING
PRADAXA 75 mg capsules have a light blue opaque cap imprinted with the Boehringer Ingelheim company symbol and a cream-colored opaque body imprinted with "R75". The color of the imprinting is black. The capsules are supplied in the packages listed:
NDC 0597-0107-54 Unit of use bottle of 60 capsules
NDC 0597-0107-60 Blister package containing 60 capsules (10 x 6 capsule blister cards)
