Age Distribution of People With AF Compared With U.S. General Population Arch Int Med. 1995;155:471. Age (years) Population with Atrial Fibrillation U.S. Population U.S. Population (x 1000) 5–9 <5 10–14 15–19 20–24 25–29 30–34 35–39 40–4450–5460–6470–7480–8490–94 45–4955–5965–6975–7985–89>95 AF Population (x 10) 0 10.000 20,000 30,000 0 100 200 300 400 500
Warfarin for Atrial Fibrillation Limitations Lead to Under-treatment <5555-6465-7475-84 85 44% 58% 61% 57% 35% Age (years) Warfarin Use in Eligible Patients (%) 55% Overall Use Go A et al. Ann Intern Med 1999;131:927.
Warfarin Battling All Comers for Over a Decade Warfarin vs placebo Warfarin vs ASA Warfarin vs ASA + fixed dose wafarin Warfarin vs DTI Warfarin vs dual antiplatelet
RELY Dabigatran for stroke prevention in atrial fibrillation Non-valvular atrial fibrillation at moderate to high risk of stroke or systemic embolism (at least one high risk factor) R Warfarin 1 mg, 3mg, 5 mg (INR 2.0-3.0) N=6000 Dabigatran Etexilate 110 mg b.i.d. N=6000 Dabigatran Etexilate 150 mg b.i.d. N=6000 Primary objective: Noninferiority to warfarin Minimum 1 year follow-up, maximum of 3 years and mean of 2 years of follow-up. Primary end point: Stroke + systemic embolism
Atrial Fibrillation with At Least One Additional Risk Factor for Stroke Apixaban placebo twice daily + Warfarin (target INR 2-3) Apixaban 5 mg oral twice daily + Warfarin placebo Primary outcome: stroke and systemic embolism Other outcomes: Death, MI, bleeding Stratified by warfarin-naïve status 448 events over anticipated 2 year median follow-up; >90% power to show non-inferiority (apixaban vs warfarin upper bound of 95% CI <1.38) Randomize Double blind (n = 15,000) Age ≥ 75 years Prior stroke, TIA or SE CHF or LVEF ≤ 40% Diabetes mellitus Hypertension Age ≥ 75 years Prior stroke, TIA or SE CHF or LVEF ≤ 40% Diabetes mellitus Hypertension Warfarin/warfarin placebo adjusted by INR/sham INR based on encrypted point-of-care testing device ARISTOTLE
9 Rivaroxaban Warfarin Primary Endpoint: Stroke or non-CNS Systemic Embolism Statistics : non-inferiority, >95% power, 2.3% warfarin event rate INR target - 2.5 (2.0-3.0 inclusive) 20 mg daily 15 mg for Cr Cl 30-49 Atrial Fibrillation Randomize Double blind / Double Dummy (n ~ 14,000) Risk Factors CHF CHF Hypertension Hypertension Age 75 Age 75 Diabetes DiabetesOR Stroke, TIA or Systemic embolus Stroke, TIA or Systemic embolus At least 2 required Monthly Monitoring and adherence to standard of care guidelines