AFIB Anti-coagulation . Schirmer JACC Dec 2010;56:2067 Clinical - - PowerPoint PPT Presentation

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AFIB – Anti-coagulation

Schirmer JACC Dec 2010;56:2067

Clinical Trials - Aristotle

Grainger et al. NEJM 2011;365;981

• Apixaban 5mg bid vs Warfarin
• 18,201 subjects with at least 2 episodes of AFIB and

CHADS2 - 1 or more (mean 2.1)

• Non-inferiority design
• Stroke or systemic embolism as Primary EP
• Safety EP was major bleeding
• Apixiban previously shown to reduce risk of same EP

by 55% in those who could not take Warfarin

• Mean age 70 with 2/3 male

Clinical Trials - Aristotle

Grainger et al. NEJM 2011;365;981

Clinical Trials - Aristotle

Grainger et al. NEJM 2011;365;981

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AFIB – ROCKET AFIB

• Presented at AHA 2010
• 14000 patients with AFIB randomized to

Rivaroxaban or Coumadin

• Very high risk with 90% CHADS2 3 or above
• 55% had a previous CVA
• CVA and systemic embolism over 40 months

20 40 60 80 100 120 240 360 480 600 720 840

Days since randomization Cumulative event rate (%)

Rivaroxaban vs Warfarin: ROCKET AF Trial

14,264 Patients (Blinded)

Rates of major bleeding Rivaroxaban Warfarin P

• Any

2.13 3.09 <0.001

• Fatal

0.4 0.8 0.003

• Intracranial hem

0.33 0.80 <0.001 No./100 patient-year

1 2 3 4 5 6 120 240 360 480 600 720 840

Per-protocol population Events: stroke or systemic embolism

Warfarin

HR 0.79 (0.66-0.96) P<0.0001 for noninferiority

Rivaroxaban

3143509-1

Patel: NEJM, 2011

With permission B. Gersh 2012

3169948-4

Summary of Recent Clinical Trials

*Creatine clearance <30 mL/min

Dose Endpoints

• Stroke/systemic

embolism 150 mgm bid 110 mgm bid (not in USA) 75 mgm bid* 20 mgm/day 5 mgm bid** Superiority ( age >75 yrs with 150 mgm bid ) Noninferior

**2.5 mgm bid in high-risk pts Age >80 yrs Wt <60 kg Creatinine >1.5 mgm dL

Drug Dabigatran Rivaroxaban Apixiban Target Thrombin Factor Xa Factor Xa 150 mgm bid – superiority 110 mgm bid – noninferior

• Bleeding
• Intracranial

hemorrhage

With permission B. Gersh 2012

Clinical Trials – Atlas TIMI 51

Mega et al. NEJM 2011;365 (Nov 2011)

• Rivaroxaban 2.5 or 5 mg bid vs placebo
• 15,526 ACS patients for mean of 13 months
• Primary EP of CV death, MI or stroke
• Mean age 61
• 50% STEMI and 60% had PCI or CABG with index

event

• >90% on ASA and Plavix

Clinical Trials – Atlas TIMI 51

Mega et al. NEJM 2011;365 (Nov 2011)

Clinical Trials – Atlas TIMI 51

Mega et al. NEJM 2011;365 (Nov 2011)

Increased IC bleeding 0.6 vs 0.2 %

Clinical Trials – APPRAISE-2

• Higher risk group of ACS patients
• HR 0.95 for Apixaban vs placebo for primary EP of

death, MI and stroke

• At 12 months, event rate almost double ATLAS –

ACS2 study

Alexander et al. NEJM 2011

Clinical Trials – Stem cell infusion

Williams et al. Circ Res 2011;108:792

• 8 subjects with endovascular , intra-myocardial

injection

• Autologous bone marrow derived progenitor cells
• Injected into scar and peri-scar areas
• CMR end-point at 3, 6 and 12 months
• Novel due to looking at chronic scar patients and

evaluating reverse remodeling

• Preliminary data from TAC- HFT

Clinical Trials – Stem cell infusion

Williams et al. Circ Res 2011;108:792

• Bone marrow aspirates

– Mononuclear cells (n=4) reinfused within 4 hours – Mesenchymal cells (n=4) cultured and reinfused in 5 weeks

• Injected by catheter up to 10 areas identified by CMR

maps

• EF 20-50% and presence of scar on CMR
• CMR evaluated EF, volumes, % scar, RWM

Clinical Trials – Stem cell infusion

Williams et al. Circ Res 2011;108:792

Clinical Trials – Stem cell infusion

Williams et al. Circ Res 2011;108:792

Decrease in both ESV and EDV EF doesn’t change

Clinical Trials – Stem cell infusion

Williams et al. Circ Res 2011;108:792

Decrease in both RWM and amount of scar Early change in RWM predicted later remodeling

RWM