Life After CORAL: What Did CORAL Prove? David Paul Slovut, MD, PhD Co-director TAVR, Dir of Advanced Intervention

Transcription

1 Life After CORAL: What Did CORAL Prove? David Paul Slovut, MD, PhD Co-director TAVR, Dir of Advanced Intervention

2 No Relationships to Disclose

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4 The Need for Modern Renal Trials Increased rate of RAS diagnosis Renal revascularization performed in 16% of newly diagnosed cases of RAS in the US 1 4 previous RCTs were small and inconclusive Rates of Diagnosis and Treatment of ARAS in the United States ( ) 2 1. Kalra PA et al., Kidney Int 2005;68: Kidney Int. 2010;77:37-43

5 Half Empty (Nephrologist) Half Full (Interventionalist)

6 ASTRAL Recruitment The ASTRAL Investigators, NEJM 2009;361: Patients eligible if they had substantial anatomic atherosclerotic stenosis of at least 1 renal artery AND if the patient s doctor was uncertain if the patient would definitely have a worthwhile clinical benefit from revascularization.

7 Angioplasty and STent for Renal Artery Lesions The ASTRAL Investigators, NEJM 2009;361: w significant unilateral or bilateral RAS 403 Med Rx 94% remain on best med rx 403 Stent Assigned 308 Stent (95% success) 44 Not attempted 34 Unknown

8 ASTRAL Primary Outcome Outcomes similar between groups: --Reciprocal of serum cr (1 outcome) --Serum creatinine over time --Mean change of serum creatinine --Systolic and diastolic BP

9 ASTRAL: Time to First MI, Stroke, Vascular Death or Hospitalization for Angina, or Heart Failure 238 events in 141 pts (revasc group) 244 events in 145 pts (med rx group)

10 Medical Regimen Improved Survival ASTRAL annual mortality 8%/year US Medicare study , annual mortality 16.3% for pts w RAS 6.4% without RAS

11 ASTRAL Summary For patients with moderate to severe RAS, medical management is as effective as revascularization over a 5 year follow-up period. No differences between the arms for Blood pressure control Major renal events, major CV events Overall mortality Optimal medical regimen crucial for survival

12 ASTRAL Issues Endpoint renal function 25% GFR > 50 ml/min 40% w stenosis 50 70% Do physicians really have uncertainty about this patient s worthwhile clinical benefit from revascularization?

13 Renal artery stenting is not indicated for preservation of renal function in patients with nonobstructive renal artery stenosis and If you or a family member are planning to undergo renal artery stenting, do it in a center, where the complication rate is substantially less than reported in ASTRAL.

14 CV Outcomes in Renal Atherosclerotic Lesions Cooper CJ et al. NEJM 2014;370:13-22 RCT 947 participants with atherosclerotic RAS Systolic HTN on > 2 more anti-htn OR CKD (egfr < 60 ml/min/1.73^2) Severe RAS: defined angiographically as 80 99% stenosis OR stenosis > 60 but < 80% of the diameter of an artery with a systolic pressure gradient > 20 mm Hg Primary endpoint: Composite of death from CV or renal causes, MI, CVA, hospitalization for CHF, progressive renal insufficiency, or need for RRT

15 CORAL Cooper CJ et al. NEJM 2014;370: screened 947 randomized 4375 not enrolled 801 declined 210 withdrawn by MD 1866 anatomic excl 628 clinical exclude 870 other reasons Misc exclusions 459 stent + meds 472 meds only

16 CORAL: Survival Cooper CJ et al. NEJM 2014;370:13-22

17 CORAL: Subgroup Analysis Cooper CJ et al. NEJM 2014;370:13-22 None of subgroup analysis was positive Age > 70 years, Gender, Race Cr > 1.6 mg/dl Estimated GFR > 45 ml/min/1.73^2 Diabetes Global renal ischemia Baseline SBP > 160 mmhg US vs foreign site Maximal diameter stenosis > 80%

18 CORAL: Medical Therapy Revasc. Medical P-value Anti-hypertensives 97% 99% 0.03 Medical therapy alone was associated with 20% rate of primary endpoint at two years (half expected rate of 40%) Beta-blocker 46% 55% 0.02 ACE-I or ARB 50% 43% 0.05 Anti-platelet therapy (ASA) 83% (89%) 78% (91%) NS Cholesterol lowering (statin) 86% (97%) 87% (96%) NS

19 Coral Critique: Design & Enrollment Sos TA et al. J Vasc Interv Radiol 2014;25:520-3 Protocol changes (and issues) Eliminated need for pressure gradient > 20 Eliminated need for SBP > 155 mm Hg Ostial lesions hard to assess even w core lab Recruitment extended from Only 18% of screened patients enrolled Modern randomized, controlled clinical trials of OMT versus renal stenting have demonstrated limited benefit. However, these trials frequently excluded patients that may benefit from renal artery stenting. Parikh S et al. CCI 2014

20 Renal Revasc in High-risk Presentations Ritchie J et al. Am J Kidney Dis 2014;63: patients with RAS > 50%, managed according to clinical presentation and physician/patient preference Presentation Flash pulmonary edema (n = 37) Refractory hypertension (n = 116) Rapidly declining renal function (n = 46) Renal revascularization in 29% of patients Renal revascularization not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension

21 Renal Revasc in High-risk Presentations Ritchie J et al. Am J Kidney Dis 2014;63:186-97

22 Severe Stenosis Solitary Functioning Kidney Ritchie J et al. Am J Kidney Dis 2014;63: Renal artery intervention in pts with unilateral disease (n = 242) vs in pts with solitary functioning kidney (n = 73) Intervention in pts with solitary functioning kidney is safe and improves or stabilizes renal function in 82% of pts.

23 BP Response to Renal Stenting Weinberg I et al. Cath Cardiovasc Interv 2014;83: patients in 5 prospective multicenter trials BP response defined as reduction of SBP by >10 mm Hg Complete outcome information was available in 527 Compared to baseline, 9-month BP decreased SBP ( mm Hg vs mm Hg, P<0.0001) DBP ( mm Hg vs mm Hg, P < ) 90% stent patency at 9 months Largest predictor SBP > 150 mm Hg

24 SCAI Expert Consensus Statement for Renal Artery Stenting Appropriate Use Parikh SA et al. Catheter Cardiovasc Interv 2014;84: Appropriate Care Cardiac Disturbance Syndromes (flash pulmonary edema or acute coronary syndrome (ACS)) with severe hypertension Resistant HTN Ischemic nephropathy with chronic kidney disease (CKD) with egfr < 45 cc/min and global renal ischemia (unilateral significant RAS with a solitary kidney or bilateral significant RAS) without other explanation

25 SCAI Expert Consensus Statement for Renal Artery Stenting Appropriate Use Parikh SA et al. Catheter Cardiovasc Interv 2014;84: Rarely Appropriate Care Unilateral, Solitary, or Bilateral RAS with controlled BP and normal renal function Unilateral, Solitary, or Bilateral RAS with chronic end stage renal disease on hemodialysis > 3 months Unilateral, Solitary, or Bilateral renal artery chronic total occlusion

26 RAS Patients Die from CKD (Not RAS) Cambria RP et al., J Vasc Surg 1996;24: % of patients alive at 5 years who had Cr > 2.0

27 RAS Patients Die from CKD (Not RAS) Dorros G et al., Circulation 1998;98:642-7 Patients with renal dysfunction had 5x greater risk of death than patients with normal GFR

28 Renal Stenting: No Cause, No effect ME Nahas. Nephron Clin Pract 2010;115:c73-81 ARVD is a disease of older age, invariably associated with extensive intra-renal vascular and glomerular ischemic pathology. Therefore, one would not expect that the stretching of stenosed renal arteries would improve perfusion of ischemically sclerosed glomeruli.

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30 Life After CORAL: What Did CORAL Prove? David Paul Slovut, MD, PhD Co-director TAVR, Dir of Advanced Intervention