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