What was the Time in Therapeutic Range (TTR) for warfarin in the AMPLIFY trial?

Time in Therapeutic Range (TTR) for Warfarin in the AMPLIFY Trial

The Time in Therapeutic Range (TTR) for warfarin in the AMPLIFY trial was 60.9%. 1

Background on the AMPLIFY Trial

• The AMPLIFY trial was a phase 3, multicenter, double-blind, randomized study comparing apixaban to conventional anticoagulant therapy (enoxaparin/warfarin) for the treatment of patients with acute venous thromboembolism (VTE) 1
• Patients in the warfarin arm received enoxaparin 1 mg/kg twice daily subcutaneously for at least 5 days (until INR ≥2) followed by warfarin (target INR range 2.0-3.0) orally for 6 months 1
• The mean percentage of time in therapeutic range (INR 2.0-3.0) for patients randomized to warfarin was 60.9% 1

Significance of TTR in Anticoagulation Management

• TTR is a critical measurement of the quality of warfarin therapy, with higher TTR values associated with better clinical outcomes 2
• In clinical trials, the TTR for warfarin-treated patients typically ranges from 55% to 66% 2
• In community settings, TTR has been reported to be approximately 50%, which is lower than in controlled trial environments 2
• A TTR <65% is associated with worse clinical outcomes, while optimal performance for TTR on a population level is considered to be ≥70% 2

Implications for Clinical Practice

• The TTR of 60.9% in the AMPLIFY trial is consistent with other major anticoagulation trials but falls below the optimal target of ≥70% 2
• Recent studies suggest that patient outcomes continue to improve with increasing TTR values up to ≥80%, indicating that higher TTR targets may be beneficial 3
• Factors that can improve TTR include:
  • Pharmacist-led anticoagulation clinics (shown to achieve TTR as high as 87.27% compared to 52.48% in physician-led clinics) 4
  • Longer duration of warfarin therapy (>10 years) and better medication adherence 5

Comparison to Other Anticoagulants

• Direct oral anticoagulants (DOACs) like apixaban have a predictable pharmacodynamic profile and do not require routine coagulation monitoring, which is an advantage over warfarin 2
• In the AMPLIFY trial, apixaban was shown to be noninferior to enoxaparin/warfarin for the primary endpoint of recurrent symptomatic VTE or VTE-related death over 6 months of therapy 1
• The relative risk for VTE or VTE-related death was 0.84 (95% CI, 0.60-1.18) for apixaban compared to enoxaparin/warfarin 1

Common Pitfalls in Warfarin Management

• Failure to recognize that TTR is a critical determinant of warfarin's efficacy and safety profile 2
• Not adjusting warfarin management strategies when TTR is suboptimal (<65%) 2
• Overlooking the importance of patient education about warfarin, as only 40.2% of patients in one study received proper education, which can impact adherence and TTR 5
• Assuming that simple dosing algorithms alone can improve TTR without addressing other factors affecting anticoagulation control 6

The TTR of 60.9% in the AMPLIFY trial represents typical warfarin management in clinical trials but highlights the challenges of maintaining optimal anticoagulation control with vitamin K antagonists compared to newer direct oral anticoagulants.