CORAL Trial Aftermath: What Do We Do Now? Renal Revascularization in Perspective Michael R. Jaff, DO Massachusetts General Hospital Boston, Massachusetts, USA
Michael R. Jaff, DO Conflicts of Interest Consultant Abbott Vascular (non-compensated) Boston Scientific (non-compensated) Cardinal Health Cordis Corporation (non-compensated) Covidien (non-compensated) Ekos Corporation (DSMB) Medtronic (non-compensated) Micell, Inc Primacea Equity Access Closure, Inc Icon Interventional, Inc I.C.Sciences, Inc Janacare, Inc MC10 Northwind Medical, Inc. PQ Bypass, Inc Primacea Sano V, Inc. Vascular Therapies, Inc Board Member VIVA Physicians (Not For Profit 501(c) 3 Organization) www.vivapvd.com CBSET January 2015 2
Prevalence of Atherosclerotic RAS at Cardiac Catheterization Study, Year n ARAS >30% (%) ARAS >50% (%) Bilateral (%) Vetrovec et al, 1989 116 29% 23% 29% Harding et al, 1992 1302 29% 15% 28% Jean et al, 1994 196 33% 18% - Rihal et al, 2002 297 34% 19% 19% Weber-Mzell et al, 2002 177 25% 11% 26% White, et al. Circ. 2006;114:1892-1895.
Atherosclerotic RAS Is Bad Cardiovascular Mortality Arch Intern Med. 2005;165:207.
The Mechanisms of Renovascular Hypertension Have Been Well Described Garovic, VD, et al. Circ. 2005;112:1362-1374.
Relation Between Renal Artery Stenosis, Hypertension, and Chronic Renal Failure Safian, et al. N Engl J Med. 2001;344:410.
Do You Think These Patients with ARAS and These Scenarios Warrant Intervention? Dialysis-dependent renal failure Chronic renal insufficiency Refractory/resistant hypertension Cardiac disturbance syndrome Need for use of ACEI/ARB Unilateral renal artery stenosis
N Engl J Med. 2014;370:13-22.
Methods Open-label, randomized, international, multicenter controlled clinical trial All received medical therapy: BP, diabetes, and lipids to goal, with participants provided free: Candesartan ± hydrochlorothiazide (Atacand ) Atorvastatin + Amlodipine (Caduet ) Antiplatelet therapy N Engl J Med. 2014;370:13-22.
Inclusion Criteria Clinical syndrome: Hypertension 2 anti-hypertensive medications, OR Renal dysfunction defined as Stage 3 or greater CKD -AND- Atherosclerotic renal artery stenosis: Angiographic: 60% and <100%, OR Duplex: systolic velocity of >300 cm/sec, OR Core lab approved MRA, OR Core lab approved CTA N Engl J Med. 2014;370:13-22.
Primary Endpoint Composite of major cardiovascular or renal events: Cardiovascular or renal death Stroke Myocardial infarction Heart failure hospitalization Progressive renal insufficiency Permanent renal replacement therapy N Engl J Med. 2014;370:13-22.
Baseline Characteristics No significant differences in clinical and angiography characteristics Approximately 20% global ischemia Stenosis severity similar to FDA approval trials 1-3 Baseline Characteristics of the Study Population According to Treatment Group Characteristic Stent + Medical Medical N = 459 N = 472 Age (years) 69.3 ± 9.4 69.0 ± 9.0 Male gender (%) 51.0 48.9 White race (%) 91.5 90.9 Black race (%) 7.0 7.0 Body mass index (kg/m 2 ) 28.2 ± 5.3 28.7 ± 5.7 Systolic blood pressure (mmhg) 149 ± 23.2 150.4 ± 23.0 Estimate GFR (ml/minute) 58.0 ± 23.4 57.4 ± 21.7 Medical history and risk factors (%) Diabetes 32.4 34.3 Prior myocardial infarction 26.5 30.2 History of heart failure 12.0 15.1 Smoking in past year 28.0 32.2 Angiography % stenosis (core lab) 67.3 ± 11.4 66.9 ± 11.9 % stenosis (investigator) 72.5 ± 14.6 74.3 ± 13.1 Global ischemia (%) 20.0 16.2 Bilateral disease (%) 22.0 18.1 1. Rocha-Singh K, et al. ASPIRE-2. JACC. 2005;46:776-83. 2. Rocha-Singh K, et al. RENAISSANCE. CCI. 2008;72:853-62. 3. Jaff MR, et al. HERCULES. CCI. 2012;80:343-50. N Engl J Med. 2014;370:13-22.
Results: Periprocedural Clinical Complications No participant required dialysis within 30 days of randomization 1/459 (0.2%) in-stent + medical therapy initiated dialysis between 30 and 90 days after randomization 1 stroke resulting in death, day of randomization, Medical Therapy Only group. N Engl J Med. 2014;370:13-22.
Primary Endpoint N Engl J Med. 2014;370:13-22.
Results: Subgroups P Value for Interaction Stent vs Medical Therapy
Results: Systolic Blood Pressure p = 0.03
Who Was Excluded from CORAL? Nonatherosclerotic causes (ie, FMD) CKD with serum creatinine >4.0 mg/dl Kidney length <7.0 cm Lesion requiring more than a single stent Hospitalization for CHF within 30 days In-stent restenosis Contralateral renal artery intervention within past 9 months
Study Overview Patient-level data from 901 patients (117 centers) in 5 prospective multicenter FDA-approved IDE studies of renal artery stent revascularization was pooled Associations of BP reduction were determined by logistic regression Catheter Cardiovasc Intervent. 2014;83:603-9.
Included studies Study Device Number of Subjects Selected Inclusion Criteria HERCULES RX Herculink Elite 202 Uncontrolled BP and suboptimal PTA SOAR Bridge TM balloon expandable stent 186 Uncontrolled BP and failed PTA RENAISSANCE Express SD Renal Premounted Stent System RESTORE ASPIRE ParaMount XS DoubleStrut balloon expandable stent Palmaz Balloon expandable stent 100 Uncontrolled BP and suboptimal PTA, renal dysfunction (Cre<3.0 mg/dl), recurrent flash pulmonary edema, or any combination thereof 205 Severe HTN 208 Uncontrolled BP and suboptimal PTA Catheter Cardiovasc Intervent. 2014;83:603-9.
Blood Pressure (mmhg) Blood Pressure Response p<0.0001 180 160 140 120 100 80 60 40 20 0 164 146 Systolic BP Pre Post 79 76 Diastolic BP p<0.0001 Catheter Cardiovasc Intervent. 2014;83:603-9.
Results of Multivariable Logistic Regression Models Testing Clinical Variables Associated with BP Response Predictor Clinical variables Baseline systolic blood pressure, 10 mmhg increase Baseline diastolic blood pressure, 10 mmhg increase Odds Ratio (95% CI) P Value 1.76 (1.53-2.03) <0.0001 1.09 (0.92-1.30) 0.32 Catheter Cardiovasc Intervent. 2014;83:603-9.
So, What Do We Know? Atherosclerotic renal artery stenosis is common It connotes bad outcomes, even worse than in those patients with coronary artery disease alone Optimal medical therapy is generally all you need for CORAL-eligible patients There is undoubtedly a population of patients who need renal artery intervention ie, cardiac disturbance syndromes The future of reimbursement for renal artery stenting is very murky
PSV 273 cm/sec Lt Kidney 10.2 cm 6/5/12 PSV 286 cm/sec Lt Kidney 8.8 cm 7/15/14
The Global Education Course for Vascular Medicine and Intervention November 2-5, 2015 Wynn Las Vegas www.vivaphysicians.org Rich Educational Content Beyond the Meeting www.viva365.org
CORAL Trial Aftermath: What Do We Do Now? Renal Revascularization in Perspective Michael R. Jaff, DO Massachusetts General Hospital Boston, Massachusetts, USA