Post on 07-Aug-2015
Should NOACs Replace Warfarin
Should NOACs Replace Warfarin
Anticoagulants – historical development
1916 1924 1936 1940 1950s 20061970s 1976 1980s 1990s 2001
Oral
Injection
Spoiled sweet clover
Dicoumaroldiscovered
Warfarinclinical use
Warfarin / Vitamin Kmechanism
High / low doseWarfarin / INR
Warfarinclinical trials
Heparindiscovered
Heparinclinical use
Continous heparininfusion/
aPTT
LMWHdiscovered
LMWHclinical trials
Pentasaccharideclinical trials
Ximelagatranclinical trials
DabigatranRivaroxabanApixaban AZD0837
Indications for Anticoagulation
• Atrial Fibrillation (AF)
• DVT/PE treatment and prevention (VTE)
• Mechanical Valve Replacement
• Cardiomyopathy
• Thrombophilias
• Antiphospholipid Syndrome (APLS)
Features of an ideal anticoagulant
• High efficacy to safety index .
• Predictable dose response .
• Rapid onset of action .
• Availability of a safe antidote .
• Freedom from side effects .
• Minimal interactions .
Warfarin is Underused
Warfarin is underused - Why?
Patient factors• Refusal, perceived inconvenience.• Responsibility associated with INR monitoring.• Inadequate knowledge.
Physician factors • Over-estimation of potential bleeding risk.• Safety & monitoring factors.
LIMITATIONS OF VKA THERAPY
Routine coagulationmonitoring
Slow onset/offset of action Warfarin resistance
Numerous drug–druginteractions
Numerous food–druginteractions
Narrow therapeuticwindow (INR range 2.0–3.0)
INR = International normalized ratio; VKA = vitamin K antagonist.Ansell J, et al. Chest 2008;133;160S-198S. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008;22:129-137.Nutescu EA, et al. Cardiol Clin 2008;26:169-187.
VKA therapy has several limitations
that make it difficult to use in practice
Frequent doseadjustments
Unpredictableresponse
RE-LY®: Randomized Evaluation of Long-term anticoagulant therapY
RE-LY Results
Major BleedingISTH definition
Apixaban 327 patients, 2.13% per year Warfarin 462 patients, 3.09% per yearHR 0.69 (95% CI, 0.60–0.80); P<0.001
No. at RiskApixaban 9088 8103 7564 5365 3048 1515Warfarin 9052 7910 7335 5196 2956 1491
31% RRR
RESULTS
Candidate for NOAC
• Pts experiencing difficulty in controlling their INR despite the best effort available.
• Pts who are at high risk for warfarin complications.
• Pts who are at high risk for drug interactions.• Pts who prefer a drug that is not interfering
with lifestyle.
PATIENTS WITH AF WHO SHOULD STILL BE CONSIDERED FOR WARFARIN
• Patients with renal disease (Cr cl <30 mL/min). • Mechanical valve prosthesis.• Valvular AF.• Patients suffered adverse events while taking
dabigatran or rivaroxaban who still require anticoagulant therapy.
• Patients who have concerns about compliance with a twice daily dose.
• Finally, patients who simply cannot afford the new agents should be treated with warfarin.
CONCLUSIONNOAC ( New Oral AntiCoagulants ) vs Warfarin :• Non-inferior for prevention of stroke/embolism in AF.
• Probable reduced hemorrhagic stroke rate.
• Reduced rate of fatal bleeding events.
• Increased incidence of GI bleeds.
• Higher cost of drug .
• Warfarin still has its indications over NOAC until trials prove their superiority in these indication . • Warfarin is still the drug of choice for our poor patients .
THANK YOU FOR ATTENTION
PROPOSED AND INVESTIGATIONAL STRATEGIES FOR SERIOUS BLEEDING