NOAK Use and Current Evidence Lecture

Introduction

• Speaker: Dr. Anand
• Topic: NOAK use and current evidence
• Main Points:
  • Overlap with previous talks on trials
  • Importance of understanding trials and current evidence

NOAK Overview

• NOAK: Newer Oral Anticoagulants (Direct Oral Anticoagulants)
• Function: Act on coagulation pathway (extrinsic, intrinsic, common pathways)

FDA Approved Prophylactic Indications

• Orthopedic Surgery (prevention of VTE):
  • Rivaroxaban: 2011
  • Apixaban: 2014
  • Edoxaban: 2015
• Stroke Prevention (Non-valvular AF):
  • Dabigatran, Rivaroxaban, Apixaban, Edoxaban: various years
• Treatment of Venous Thromboembolism (VTE):
  • All NOAKs including Betrixaban (recent: 2017)
• Acute Coronary Syndrome (ACS):
  • Rivaroxaban, Apixaban: in guidelines but not formally FDA approved

Key Differences Between NOAKs and Warfarin

• NOAKs:
  • Fixed dose, no INR monitoring, less bleeding risk, higher cost
• Warfarin:
  • Predictable, liver excretion, requires INR monitoring, dietary interactions, narrow therapeutic window

Evidence and Trials

• Largest Meta-analysis in Lancet (2014):
  • 72,683 patients, 48 RCTs
  • NOAKs vs. Warfarin
  • Reduced stroke/systemic thrombosis, all-cause mortality, intracranial bleed
  • Higher GI bleed
  • Low-dose NOAKs: ineffective for stroke/systemic thrombosis

Landmark Trials

• RE-LY (2009):
  • Dabigatran vs. Warfarin
  • 110 mg: similar efficacy, less bleeding
  • 150 mg: higher efficacy, similar bleeding
• ROCKET-AF (2011):
  • Rivaroxaban vs. Warfarin
  • Non-inferior efficacy, less intracranial/fatal bleed
• ARISTOTLE (2011):
  • Apixaban vs. Warfarin
  • Higher efficacy, less major/intracranial bleed
• ENGAGE-AF (2013):
  • Edoxaban (high and low dose) vs. Warfarin
  • High dose: more effective, low dose: less effective
  • Less major bleed, less cardiovascular death
• Observational Study: Apixaban in end-stage renal disease
  • Higher dose effective for stroke/systemic thrombosis
  • Less bleeding risk
• Recent Study (2024): Apixaban vs. Aspirin in subclinical AF
  • Lower stroke/systemic thrombosis
  • Higher major bleed compared to aspirin

Recommendations and Dosages

• Atrial Fibrillation:
  • Apixaban: 5 mg BD (2.5 mg for specific conditions)
  • Dabigatran: 150 mg BD
  • Edoxaban: 60 mg OD (30 mg for low body weight/clearance)
  • Rivaroxaban: 20 mg OD (15 mg for low clearance)
• Treatment of VTE:
  • Initial: LMW Heparin, followed by NOAK (Dabigatran, Edoxaban)
  • Apixaban 10 mg BD for 7 days, then 5mg BD
  • Rivaroxaban 15 mg BD for 21 days, then 20 mg OD
• Prevention in Cancer and Orthopedic Surgeries:
  • Apixaban: 2.5 mg BD
  • Dabigatran: 150 mg BD
  • Rivaroxaban: 10 mg OD
  • Edoxaban: 60 mg OD

Considerations

• Endorsements: Various guidelines support these recommendations
• Concerns: Most trials are Pharma-funded, not institution driven

Take-Home Messages

• NOAKs: Effective in both prophylaxis and treatment
• Main Use: Stroke prevention in AF, VTE prevention in orthopedic surgeries, treatment of VTE
• Physiological Plausibility: Validated by current evidence
• Caution: Consider Pharma funding bias in trials

Call to Action

• Submit Work: Journal of Acute Care (quarterly publications)
• Website: Visit Pra.com for more information.

Conclusion

• Thank you for attending!