XI. Treatment of Hypertension in Association With Renovascular Disease

Prevention and Treatment

Subgroup Members: Marcel Ruzicka, MD, PhD; Sheldon Tobe, MD, MSc(HPTE); Kevin Burns, MD; Ramesh Prasad, MBBS, MSc; Michel Vallée, MD, PhD
Central Review Committee: Stella S. Daskalopoulou, MD, PhD; Kaberi Dasgupta, MD, MSc; Kelly B. Zarnke, MD, MSc; Kara Nerenberg, MD, MSc; Alexander A. Leung, MD, MPH; Kevin C. Harris, MD, MHSc; Kerry McBrien, MD, MPH; Sonia Butalia, BSc, MD; Meranda Nakhla, MD, MSc
Chair: Doreen M. Rabi, MD, MSc
This information is based on the Hypertension Canada guidelines published in Leung, Alexander A. et al. Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol 2017; 33(5): 557-576.

Guidelines

  1. Patients with hypertension attributable to atherosclerotic renal artery stenosis should be primarily medically managed because renal angioplasty and stenting offers no benefit over optimal medical therapy alone (Grade B).
  2. Renal artery angioplasty and stenting for atherosclerotic hemodynamically significant renal artery stenosis could be considered for patients with uncontrolled hypertension resistant to maximally tolerated pharmacotherapy, progressive renal function loss, and acute pulmonary edema (Grade D).
  3. Patients with confirmed renal FMD should be referred to a hypertension specialist (Grade D; new guideline).
  4. In patients with hypertension attributable to FMD-related renal artery stenosis, revascularization should be considered (Grade D; new guideline).
  5. Renal artery angioplasty without stenting is recommended for treatment of FMD-related renal artery stenosis. Stenting is not recommended unless needed because of a periprocedural dissection. Surgical revascularization should be considered in case of complex lesions less amendable to angioplasty, stenosis associated with complex aneurysm, and restenosis despite 2 unsuccessful attempts of angioplasty (Grade D; new guideline).

Background

1. Patients with hypertension attributable to atherosclerotic renal artery stenosis (RAS) should be managed medically primarily because renal angioplasty and stenting offers no benefit over optimal medical therapy alone (Grade B).

2. Renal artery angioplasty and stenting for atherosclerotic hemodynamically significant RAS could be considered for patients with uncontrolled hypertension resistant to maximally tolerated pharmacotherapy, progressive renal function loss, and acute pulmonary edema (Grade D).

The original rationale for the recommendations and evidence underlying assigned grades were outlined in the 2000 Recommendations (1); however, these revised recommendations for hypertension associated with atherosclerotic RAS, now reflect recently published data from the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) trial (2) and a meta-analysis incorporating CORAL results (3). Changes emphasize optimization of medical management and limitation of the use of renal revascularization procedures.  In particular, it is recommended that hypertensive patients with RAS be managed with good BP control to appropriate targets, a high dose of a high-potency statin for lipid management, good glycemic control, and appropriate antiplatelet therapy. Management should also include adoption of health behaviours appropriate to risk profile.

The National Institutes of Health-funded CORAL trial enrolled 947 patients with RAS of at least 80% or at least 60% and evidence of hemodynamic pressure gradients (2). In addition, these patients had either hypertension not controlled with two or more drugs or declining renal function. All subjects had their cardiovascular risk factors (blood pressure [BP], lipids, glycemic control, and antiplatelet therapy) managed systematically according to a protocol, with 460 patients assigned randomly to stenting of stenotic renal arteries.

The primary composite outcome included cardiovascular or renal death, myocardial infarction (MI), stroke, heart failure hospitalization, progression of renal dysfunction, or requirement of renal replacement therapy. After a median follow-up of 43 months, renal artery stenting did not improve either the primary composite outcome or any of its constituent components. Systolic blood pressure (SBP) was trivially reduced by renal artery stenting.

These results are congruent with results of seven other smaller trials. When combined, meta-analyses of the aggregate 2223 patients from these eight trials did not detect a favourable mortality, stroke, heart failure, or renal preservation effects of revascularization for RAS (3). BP was not reduced and, in aggregate, antihypertensive drug use was only reduced by less than half a daily dose per day.

Despite the null results of CORAL and other randomized controlled trials, concern remains that in aggregate, low trial thresholds for subject inclusion might have resulted in underrepresentation of less common but more severely affected patients. This latter group could include those patients with more severe and bilateral stenosis associated with progressive decline in renal function, recurrent pulmonary edema, and refractory hypertension despite use of four or more drugs. In addition, endpoint estimates for most clinical outcomes in CORAL and the meta-analysis lie slightly on the side of favouring renal artery revascularization and with wide confidence intervals. For these reasons, in the expert opinion of the CHEP RTF, renal angioplasty and stenting could be considered in these uncommon refractory cases.

However, it is also readily evident that the presence of renal artery stenosis (RAS) is predictive of atherosclerotic disease in other vascular beds (4), suggesting patients with RAS should be evaluated carefully for occult vascular disease and should have their hypertension controlled with drug therapy to targets outlined in Section IV (5). In absence of data indicating any one class of agents is superior in treatment of renovascular hypertension, any of the agents recommended in Section II may be appropriate (although angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor antagonists [ARBs] should be used with caution due to potential for inducing ischemia in a kidney with a stenotic artery).

Additionally, caution with appropriate monitoring of serum creatinine and potassium with use of renin-angiotensin-aldosterone system (RAAS) inhibitors is still recommended, particularly if bilateral RAS disease is present; however, this caution does not preclude use of these drugs. Most patients will have been treated with a RAAS inhibitor before diagnosis of renovascular hypertension is made or suspected. In randomized controlled trials, such as CORAL, a RAAS inhibitor was a proximal part of treatment protocol (2).

Anticipated soon is inclusion of guidance specific to non-atherosclerotic causes, such as fibromuscular dysplasia, in which estimates of benefit on hypertension outcomes might be larger (16). Certainly in younger patients with fibromuscular dysplasia lesions, results with percutaneous transluminal renal angioplasty were comparable with surgical revascularization (8). Based on expert opinion, percutaneous transluminal renal angioplasty is often performed in patients with fibromuscular dysplasia.  However, there is a paucity of randomized data from such patients and nontrivial risks of procedure-related vascular complications (16).

References

  1. McAlister FA, Levine M, Zarnke K, Campbell NRC, et al, for the Canadian Hypertension Recommendations Working Group. The 2000 Canadian recommendations for the management of hypertension: Part one – Therapy. Can J Cardiol 2001;17:543-59.
  2. Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med 2014;370:13-22.
  3. Bavry AA, Kapadia SR, Bhatt DL, Kumbhani DJ. Renal artery revascularization: updated meta-analysis with the CORAL trial. JAMA Intern Med 2014;174:1849-51.
  4. Zarnke KB, Levine M, McAlister FA, et al., for the Canadian Hypertension Recommendations Working Group. The 2000 Canadian recommendations for the management of hypertension: Part 2 – diagnostics. Can J Cardiol 2001 Dec;17(12):1249-63.
  5. Zierler RE, Bergelin RO, Polissar NL, et al. Carotid and lower extremity arterial disease in patients with renal artery atherosclerosis. Arch Intern Med 1998;158:761-7.
  6. Dorros G, Jaff M, Mathiak L, Lowe A, Murphy K, He T. Four year follow-up of Palmaz-Schatz stent revascularization as treatment of atherosclerotic renal artery stenosis. Circulation 1998;98:642-7.
  7. Blum U, Krumme B, Flugel P, et al. Treatment of ostial renal artery stenoses with vascular endoprostheses after unsuccessful balloon angioplasty. N Engl J Med 1997;336:459-65.
  8. Bonelli FS, McKusick MA, Textor SC, et al. Renal artery angioplasty: technical results and clinical outcome in 320 patients. Mayo Clin Proc 1995;70:1041-52.
  9. Webster J, Marshall F, Abdalla M, et al. Randomized comparison of percutaneous angioplasty vs. continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. J Hum Hypertens 1998;12:329-35.
  10. Plouin P-F, Chatellier G, Dame B, Raynaud A, for the Essai Multicentrique Medicaments vs. Angioplastie (EMMA) Study Group. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis. A randomized trial. Hypertension 1998;31:823-9.
  11. Van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal artery stenosis. N Engl J Med 2000;342:1007-14.
  12. Chabova Y, Schirger A, Stanson AW, McKusick MA, Textor SC. Outcomes of atherosclerotic renal artery stenosis managed without revascularization. Mayo Clin Proc 2000;75:437-44.
  13. Watson S, Hadjipecrou P, Cox SV, et al. Effect of renal artery scenting on renal function and size in patients with atherosclerotic renovascular hypertension. Circulation 2000;102:1671-7.
  14. Beutler JJ, Van Ampting JMA, Van de Yen PJG, et al. Long-term effects of arterial stenting on kidney function for patients with ostial atherosclerotic renal artery stenosis and renal insufficiency. J Am Soc Nephrol 2001;12:1475-8.
  15. Van de Yen PJG, Kaatee R, Beutler JJ, et al. Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial. Lancet 1999;353:282-6.
  16. Trinquart L, Mounier-Vehier C, Sapoval M, Gagnon N, Plouin PF. Efficacy of revascularization for renal artery stenosis caused by fibromuscular dysplasia: a systematic review and meta-analysis. Hypertension 2010;56:525-32.