Early Intervention in Type B Dissection: Results From the INSTEAD XL Trial None Disclosures Jade S. Hiramoto, MD, MAS April 4, 2014 Outline Background Current treatment Results from INSTEAD trial Results from INSTEAD XL trial (extended for late follow-up) High risk subpopulations with type B dissection Conclusions Acute Type B Dissection Incidence: 0.5-2.1/100,000 person years Typical patient: male, age 60-65 years, history of hypertension Up to 30% will present with a complicated type B dissection - Rupture - Malperfusion - Unremitting pain - Uncontrolled hypertension - Worsening of imaging studies Thoracic endovascular aortic repair (TEVAR) considered life-saving in complicated cases 1
Uncomplicated Type B Dissection Medical therapy has been standard of care - Close ICU monitoring - Control of blood pressure, heart rate, and pain - β-blockers staple of optimal medical management Large databases: ~90% of patients can be successfully managed in-hospital with medical therapy alone Why Intervene on Uncomplicated Type B Dissection? Long-term results after discharge less than ideal - 5-year survival ranges from 48% to 82% (of those discharged alive from hospital) 25% to 50% treated medically develop late aortic-related complications - Aneurysmal degeneration - Rupture - Malperfusion Why Intervene on Uncomplicated Type B Dissection? The Investigation of STEnt Grafts in Aortic Dissection (INSTEAD) Trial Ideal medical management after discharge not well-defined - β-blockers vs ACE-inhibitors vs ARB s - Patient compliance after d/c difficult TEVAR may decrease late complications and improve long-term survival Although TEVAR considered life-saving in complicated type B dissection, role in improving outcomes in uncomplicated dissection unknown First randomized trial to compare elective TEVAR to optimal medical therapy (OMT) Randomized 140 patients to elective stentgraft placement + OMT (n=72) to OMT alone (n=68) - Stable clinical condition 2 weeks after index dissection 2
The Investigation of STEnt Grafts in Aortic Dissection (INSTEAD) Trial INSTEAD: Results TALENT stent grafts (Medtronic, Inc.) Primary end point - All-cause death at 2 years Secondary end points - Aorta-related death - Progressive aortic pathology - Aortic remodeling INSTEAD: Aortic Remodeling INSTEAD: Conclusions Elective TEVAR in clinically stable, low-risk patients does not improve 2-year survival, despite favorable aortic remodeling - Spinal injury in 2.8% of patients Trial results support complication-specific approach instead of TEVAR for all type B dissections Deferred endovascular therapy is feasible and safe in those who fail to respond to medical management 3
INSTEAD: Trial Limitations INSTEAD XL 11.2% of patients in medical arm crossed over to TEVAR within 12 months Trial underpowered because of high survival rates in OMT group High mortality in TEVAR group Inclusion of patients up to one year following acute presentation: heterogeneous risk Unknown/unclear long-term benefit of TEVAR for uncomplicated type B dissection Landmark statistical analysis of years 2-5 after index intervention - Primary end point: All-cause mortality - Secondary end points: Aorta-related death Progression of disease INSTEAD XL INSTEAD XL: All Cause Mortality What is a landmark analysis? - Survival estimates calculated from that time point - Patients who die before that landmark time point are excluded from analysis - Most powerful when risk altering intervention occurs early and outcomes of interest are not common at this early study period - Loss of power - Loss of the effects of randomization 11.1% 2.1% 16.9% 0% 19.3% 11.1% Landmark analysis at 2-year breakpoint Kaplan-Meier survival analysis 4
INSTEAD XL: Aorta-Specific Mortality INSTEAD XL: Progression of Disease and Aorta-Specific Events 16.9% Landmark analysis at 2-year breakpoint 28.1% Landmark analysis at 2-year breakpoint 6.9% 2.9% 0% 4.1% 46.1% 19.3% 27.0% 6.9% Kaplan-Meier survival analysis Kaplan-Meier survival analysis INSTEAD XL: Aortic Remodeling INSTEAD XL: Causes of Death Preventable with early TEVAR? All patients in OMT arm that ruptured during F/U had entry tear >10 mm 5
INSTEAD XL: Conclusions TEVAR in subacute phase of type B dissection: - Induces aortic remodeling - Reduces aorta-related mortality at 5 years Early hazard of TEVAR counterbalanced by prevention of late complications and crossover procedures Our future approach: TEVAR as first line therapy in order to heal and remodel dissected aorta - Which patients? Subpopulations at Risk for Late Complications: Partial False Lumen Thrombosis Tsai TT et al; NEJM 2007 Subpopulations at Risk for Late Complications: Large False Lumen* Subpopulations at Risk for Late Complications Increased late complications - Patent false lumen - Large false lumen - Large entry tear - Aortic diameter 40mm - Primary entry tear located at concavity of aortic arch (inner curve) *includes patients with type A dissection Song J et al; J Am Coll Cardiol 2007 Increased in-hospital mortality - Recurrent/refractory pain - Refractory hypertension 6
TEVAR as Primary Treatment for Subacute Uncomplicated Type B Dissection Who Should We Not Treat? Life expectancy > 2 years AND: - Recurrent/refractory pain - Refractory hypertension - Large entry tear (> 10mm) - Partial thrombosis of false lumen - Aortic diameter > 4cm, especially in setting of large false lumen Patients with life expectancy < 2 years Complete false lumen thrombosis Small entry tears (< 10 mm) Difficult anatomy (requiring significant de-branching) ADSORB: Acute Dissection: Stent graft OR Best medical therapy Randomized trial for acute, uncomplicated type B dissection - Time from symptom onset to treatment 14 days - GORE TAG device + OMT to OMT alone Primary efficacy endpoint at one year = freedom from one or more of the following: - Incomplete or no false lumen thrombosis - Aortic dilatation - Aortic rupture 7