VKA is still superior to NOAC in some situations

VKA is still superior to NOAC in some situations Dr. Reginald Liew MA, MBBS (Hons), PhD (Lond), FRCP (UK), FESC, FACC Senior Consultant Cardiologist, Gleneagles Hospital Asst. Prof. Duke-NUS Graduate Medical School, Singapore No conflict of interests to disclose Warfarin vs placebo 0.33 [0.24, 0.45] Warfarin vs ASA 0.59 [0.40, 0.86] Warfarin vs all FLD warfarin 0.36 [0.23, 0.58] Warfarin vs Ximelagatran 1.04 [0.77, 1.40] RR (fixed) [95% Cl] Favours adjusted warfarin Favours other treatment 13 trials reviewed (n=14,423) AF, atrial fibrillation; ASA, acetylsalicylic acid; CI, confidence interval; FLD, fixed low dose 0.1 1 10 100 0.01 Lip et al. Thromb Res 2006 Comparison Warfarin : Effective for stroke prevention in AF Meta analysis of dose adjusted agents The promise of new oral anticoagulants 1. Ansell J et al, 2004; 2. Mueck W et al, 2007; 3. Mueck W et al, 2008; 4. Mueck W et al, 2008; 5. Raghavan N et al, 2009; 6. Shantsila E, Lip GY. 2008. Less impact on patient’s daily life Improved QoL Less labour- intensive Reduced administrative costs Improved compliance Improved efficacy and safety Reduced potential for food and drug interactions Simplified dosing regimen No dietary restrictions Predictable anticoagulation No need for routine coagulation monitoring Can be given at fixed doses RCT data showing that NOAC are: • As effective as VKA to in stroke/ TE prevention in AF patients • Associated with lower rates of ICH Why then continue to use VKA?  Medical reasons  Patients with mechanical heart valves  Patients who need to have anticoagulation quickly reversed if required  Patients with inherited thromboembolic disease  Socio-economic/ financial reasons  Patient-related reasons VKA is superior to NOAC in patients with mechanical heart valves Case 1: • 72 year old woman who had a mechanical MVR 21 years earlier • Permanent AF • Stable on VKA for many years but switched to dabigatran 110mg bd by GP after a single reading of INR 5 (no active bleeding) • Admitted to hospital 3 months later with cardiogenic shock; TEE confirmed large thrombus obstructing MV orifice • Had immediate MV surgery and MVR but died 3 days post op Atar et al. Chest 2013; 144(1):327-328 VKA is superior to NOAC in patients with mechanical heart valves Case 2: • 73 year old woman who had a mechanical bileaflet MVR 12 years earlier • Paroxysmal AF • History of GI bleed, therefore switched from VKA to dabigatran 150mg bd by GP • Admitted to hospital 2 months later with acute pulmonary oedema and cardiogenic shock; angiography showed stuck anterior mitral leaflet • At urgent surgery- large thrombus found obstructing MV • Patient died 3 hours post op Atar et al. Chest 2013; 144(1):327-328 Dabigatran versus warfarin in patients with Mechanical Heart Valves (RE-ALIGN STUDY) Method: • Phase 2 dose validation study • Pt groups: • Population A- mechanical aortic or mitral bileaflet valve replacement within past 7 days • Population B- mechanical bileaflet mitral valve > 3 months before randomization • Assigned 2:1 to receive dabigatran (150mg bd, 220mg bd or 300mg bd) or warfarin (target INR 2-3 or 2.5-3.5, depending on TE risk) • 1ry endpoint trough plasma level of dabigatran Eikelboom et al. NEJM 2013; 369:1206-14 Aim: • To evaluate the optimal dose of dabigatran in patients post mechanical valve surgery Eikelboom et al. NEJM 2013; 369:1206-14 Dabigatran versus warfarin in patients with Mechanical Heart Valves- baseline characteristics Eikelboom et al. NEJM 2013; 369:1206-14 Dabigatran versus warfarin in patients with Mechanical Heart Valves- baseline characteristics Eikelboom et al. NEJM 2013; 369:1206-14 Dabigatran versus warfarin in patients with Mechanical Heart Valves- results No significant difference in mortality 9 strokes + 3 TIA in Dabigatran group 0 strokes + 2 TIA in warfarin group [...]... visible • Patient remains well and recommend to take life-long warfarin • To consider thrombophilia screen in first degree family members • Efficacy of NOAC in patients with inherited clotting disorders not known or well tested • Warfarin is still indicated in these cases and may be superior Conclusions  NOAC are superior to warfarin in stroke prevention in AF and have an important clinical role to. .. Valves- conclusions • Possible explanation: mechanisms of thrombosis in pts with mechanical heart valves is different to that in pts with AF • Involves different factors of the coagulation cascade which warfarin is better at inhibiting (dabigatran just inhibits thrombin formation) • Data from NOAC benefits in stroke prevention in AF trials cannot be extrapolated to patients with mechanical heart valves Eikelboom... DVT • Thrombophilia screen for inherited clotting disorder showed abnormal protein S level (48%) How would you manage this patient? What anticoagulation should be used? VKA may be more effective than NOAC for treatment/ prevention of TE events in patients with inherited clotting disorders Case example (cont.): • Decided to change NOAC to warfarin • Treated with target INR 2-3 • Repeat USS leg after... to play  BUT, VKA still have an important clinical role to play and may be superior to NOAC in the following clinical situations: 1 Patients with mechanical heart valves 2 Patients who need to have anticoagulation quickly reversed if required 3 Patients with inherited thromboembolic disease Gleneagles Hospital, #03-37C, Annexe Block 6A Napier Road, Singapore T +65 6472 3703 Email: reginald.liew@hscs.com.sg... 1.94, 95% CI 0.64-5.86; P=0.24 • Statistically increased bleeding events in dabigatran group (A and B) • All major bleeding occurred in population A • Trial was stopped early due to excess of bleeding and thromboembolic events in dabigatran group • All patients subsequent changed to non-trial VKA Eikelboom et al NEJM 2013; 369:1206-14 Dabigatran versus warfarin in patients with Mechanical Heart Valves-... therapy) • Intermittent AF on ward- started on oral amiodarone When would you start anti-coagulation? What drug would you use? Effects of VKA can be reversed more quickly than NOAC Case example (cont.): • CT head at day 8 showed no brain oedema or bleeding • Discussed with neurologist, decided to start warfarin at day 10 aiming for target INR of 1.5 initially • 3 days after starting warfarin, patient... events in patients with inherited clotting disorders Case example: • 43 year old man- history of Crohn’s disease • DVT aged 26 – treated with 3 months warfarin (not further investigated at the time) • Pulmonary embolus (PE) 2 years ago after long haul flight- PE confirmed on CT PA and DVT found in leg • Treated with LMWH initially and then NOAC indefinitely • Saw me 4 months ago – leg still slightly swollen;... CVA • INR measured 1.5- corrected with iv vit K and FFP • Patient recovered after 5 days • Further anticoagulation withheld • Repeat CT head 10 days later showed hemorrhagic conversion improving Benefit of using warfarin- able to titrate to only a low level of anticoagulation; bleeding was quickly and effectively reversed VKA may be more effective than NOAC for treatment/ prevention of TE events in patients...Dabigatran versus warfarin in patients with Mechanical Heart Valves- results Increased bleeding in the dabigatran group (P