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UC UC SF SF Disclosures CORAL Trial: None Answers or More - PowerPoint PPT Presentation

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UC UC SF SF Disclosures CORAL Trial: None Answers or More Questions? Jade S. Hiramoto MD, MAS April 4, 2014 UCSF Vascular Symposium VASCULAR SURGERY UC SAN FRANCISCO VASCULAR SURGERY UC SAN FRANCISCO UC UC SF SF

  1. UC UC SF SF Disclosures CORAL Trial: • None Answers or More Questions? Jade S. Hiramoto MD, MAS April 4, 2014 UCSF Vascular Symposium VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF Atherosclerotic Renovascular Atherosclerotic Renovascular Disease (ARVD) Disease (ARVD) • Well-known cause of hypertension, renal • Many treatment options have been applied: insufficiency, ESRD - Medical therapy - Most common cause of secondary HTN, accounting - Renal artery angioplasty/stenting (RAS) for 1-5% of all cases - Open surgical revascularization • Commonly encountered • Published data, patient selection, choice of - ~7% of patients over 65 years old outcomes inconsistent across techniques - Incidental finding during imaging for other diseases or other vascular interventions – 20-45% of patients with CAD or aortoiliac disease VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO 1

  2. UC UC SF SF Renal Artery Stent vs Medical Therapy: Renal Artery Stenting (RAS) Randomized Trials • Nephropathy Ischemic ThERapy (NITER) • General consensus that renal • Renal Atherosclerotic reVascularization Evaluation revascularization should be performed (RAVE) • A RAndomised, multi-centre, prospective study - Flash pulmonary edema comparing best medical treatment versus best medical No - Acute kidney failure available treatment plus renal artery stenting in patients with results haemoDynamically relevant atherosclerotic renal ARtery stenosis (RADAR) • Many clinicians feel that patients with multidrug-resistant HTN or deteriorating renal • Benefit of STent placement and blood pressure and function should be treated lipid-lowering for the prevention and progression of renal dysfunction caused by Athersclerotic ostial - Little evidence to support this stenosis of the Renal artery (STAR) • Angioplasty and STent for Renal Artery Lesions (ASTRAL) • Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF STAR STAR: Results • Randomized clinical trial • Primary endpoint reached: - 10/64 (16%) in stent group - Efficacy and safety of stent placement in - 16/76 (22%) in medication group patients with renal stenosis and impaired - HR 0.73, 95% CI 0.33-1.61 renal function • 140 patients with stenosis > 50% and • 4 serious complications in stent group eGFR<80 mL/min per 1.73m 2 - 2 procedure-related deaths • Primary end point: 20% or greater - 1 late death secondary to infected hematoma decrease in creatinine clearance - 1 required dialysis secondary to cholesterol embolism • Treatment arms: - Medical treatment: antihypertensive, statin, • Conclusions: ASA (n=76) - Stent placement: no clear effect on progression of impaired renal function but was associated with - Stent placement and medical treatment severe procedure-related complications (n=64) VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO 2

  3. UC UC SF SF Angioplasty and Stenting for STAR: Limitations Renal Artery Lesions (ASTRAL) • All patients required to have treated blood • Multicenter, randomized, unblinded trial pressure <140/90 on entry - Revascularization with medical therapy - Medical therapy alone • 46/140 (33%) had stenosis <70% • Primary endpoint: • Only 46/64 patients in stent group actually - Rate of change of renal function over time received stent - 12 pts had stenosis <50% - Likely patients in medical group with <50% stenosis • Secondary endpoints: - Blood pressure control • Study underpowered to provide definitive - CV and renal events estimate of efficacy - Mortality VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF ASTRAL: Results ASTRAL: Patient Enrollment • 806 patients enrolled at 57 hospitals • Participant eligibility: - 59% had >70% stenosis - Substantial atherosclerotic stenosis in at - The patient ’ s doctor was uncertain that the least one renal artery suitable for - 60% had serum creatinine of > 1.7mg/dL endovascular therapy AND patient would definitely have worthwhile • Revascularization was technically clinical benefit from revascularization successful in 317/403 (79%) - 95% received a stent • Not eligible: - Required surgical revascularization - High likelihood of requiring revascularization • 24 patients (6%) in medical group within 6 months crossed over to revascularization - Previous revascularization for ARVD VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO 3

  4. UC UC ASTRAL: Results SF SF ASTRAL Investigators: Conclusions • Over 5-years, rate of progression of renal impairment favored revascularization group (p=0.06) • Substantial risks but no evidence of - Mean serum creatinine was 0.02 mg/dL lower worthwhile clinical benefit from in revascularization group (p=0.06) revascularization in patients with ARVD • No difference in SBP, renal events, major CV events, and death • However, similar to STAR…findings of study in harmony with clinical experience • 31 complications in 23 patients in - Majority of study patients would not have revascularization group undergone stent placement - 2 deaths - 3 amputations of toes or limbs VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF ASTRAL: Limitations CORAL Trial: Background • Atherosclerotic renal artery stenosis is • Over 40% of patients had < 70% stenosis common problem • No core laboratories to validate on-site stenosis measurements • Two randomized trials did not show benefit of renal artery stenting with • Primary endpoint was rate of decline in renal respect to kidney function function - 25% of enrolled patients had normal renal function • Usefulness of renal stent placement for prevention of major adverse renal and CV events is uncertain VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO 4

  5. UC UC CORAL Trial: Interventions SF SF CORAL Trial - Candesartan (angiotensin receptor blocker) ± • Medical therapy alone • Hypothesis: Optimal medical therapy with RAS in hydrochlorthiazide patients with systolic HTN reduces incidence of - Amlodipine-atorvastatin adverse CV and renal events - Doses adjusted based on blood pressure and lipid status • Primary entry criteria: - Target BP: <140/90 in patients without coexisting conditions and <130/80 in patients with diabetes or CKD - All patients will undergo renal angiography - Stenosis >60% with 20mmHg pressure gradient or >80% with no gradient • Stenting plus medical therapy - Systolic HTN > 155mmHg on > 2 antihypertensive medications - Palmaz Genesis stent - Prior to 8/2006: short-tip Angioguard used for embolic • Randomize to medical therapy alone vs RAS with protection medical therapy - After 8/2006: any FDA-approved embolic protection device could be used VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF Overall Design of the CORAL Trial CORAL Trial: Endpoints • Primary endpoint: Major CV or renal event - CV or renal death - MI - CHF - Stroke - Progressive renal insufficiency - Need for renal replacement therapy • Secondary endpoints: - All-cause mortality - Individual components of the primary end point VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO 5

  6. UC UC SF SF What Were We Supposed to CORAL Trial: Reality Learn From CORAL? • Several changes made during course of trial • The effect of revascularization for based on slow recruitment: hemodynamically significant renal artery stenosis in hypertensive patients on: - Threshold of 155 mmHg for defining HTN no longer specified - Prevention of adverse CV and renal events when - Could enroll patients without hypertension if they had added upon background of optimal medical therapy chronic kidney disease (eGFR<60ml/min/1.73m 2 ) - Severe renal artery stenosis could be identified with - Blood pressure control duplex ultrasound, magnetic resonance angiography, or computed tomographic angiography - All renal arteries with stenoses of ≥ 60% were treated - Prevention of renal dysfunction (gradient no longer required) VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO UC UC SF SF CORAL Trial: Results • Between 5/2005-1/2010, 5322 patients were screened, 947 patients randomized Coral Trial: - Medical therapy alone (n=480) Results - Stenting plus medical therapy (n=467) - Data from 16 patients excluded secondary to scientific integrity - 19 patients in medical therapy group crossed over to stenting - Median follow-up of 43 months (IQR: 31 to 55) VASCULAR SURGERY • UC SAN FRANCISCO Cooper et al; NEJM 2014 VASCULAR SURGERY • UC SAN FRANCISCO 6

  7. UC UC CORAL Trial: Results SF SF CORAL Trial: Results VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO Cooper et al; NEJM 2014 Cooper et al; NEJM 2014 UC UC CORAL Trial: Results SF SF CORAL Trial: Blood Pressure Over Time • At baseline, participants taking a mean of 2.1 ± 1.6 antihypertensive medications ± 1.5 in stent group, 3.5 ± 1.4 meds in medical Rx • Number of meds increased in both groups (3.3 group; p=0.24) ± 25.8 mmHg) and stent group (by 16.6 ± 21.2 • SBP declined in both medical Rx group (by 15.6 mmHg) VASCULAR SURGERY • UC SAN FRANCISCO VASCULAR SURGERY • UC SAN FRANCISCO Cooper et al; NEJM 2014 7

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