Renal Atherosclerotic Lesions Research Articles

Attempting to define a role for renal artery stenting: Another analysis of the CORAL trial

Modrall et al 1 Modrall G.J. Zhu H. Prasad T. Moe O. Dworkin L.D. Cutlip D.E. et al. Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the cardiovascular outcomes in renal atherosclerotic lesions trial.. J Vasc Surg. 2023; 77: 1685-1692 Abstract Full Text Full Text PDF Scopus (1) Google Scholar have reanalyzed data from the CORAL trial 2 Cooper C.J. Murphy T.P. Cutlip D.E. Jamerson K. Henrich W. Reid D.M. et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014; 370: 13-22 Crossref PubMed Scopus (666) Google Scholar to identify a role for renal artery stenting (RAS) in the subset of patients with chronic kidney disease (CKD). They demonstrated, again, that stenting does not provide a benefit compared with optimal medical therapy in terms of event-free survival, the primary end point of their analysis and the parent trial. The blood pressure response was similar between their groups, although the change in serum creatinine and the percentage of change in the estimated glomerular filtration rate (eGFR) were better in the stented group, albeit modest. A larger percentage of the stented patients had had a ≥20% increase in their eGFR (responders) vs the medical group (25.6% vs 17.1%), although the percentage of those with a ≥20% decrease in the eGFR was similar. These responders had had improved event-free, non–renal event-free, and overall survival compared with the nonresponders. However, the presence of diabetes (negative) was the only predictor of a good response. Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions trialJournal of Vascular SurgeryVol. 77Issue 6PreviewThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial with 947 patients, concluded that there was no benefit of renal artery stenting (RAS) over medical therapy. However, patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL trial. CKD is a risk factor for cardiovascular and renal morbidity. We hypothesized that improved renal function after RAS would be associated with increased long-term survival and a lower risk of cardiovascular and renal events in patients with CKD. Full-Text PDF

Predicting renal function response to renal artery stenting

ObjectiveThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions Trial found no benefit of renal artery stenting (RAS) over medical therapy, although it was underpowered to detect a benefit among patients with chronic kidney disease (CKD). A post hoc analysis demonstrated improved event-free survival after RAS for patients whose renal function improved by 20% or more. A significant obstacle to achieving this benefit is the inability to predict which patients' renal function will improve from RAS. The objectives of the current study were to identify predictors of renal function response to RAS. MethodsThe Veteran Affairs Corporate Data Warehouse was queried for patients who underwent RAS between 2000 and 2021. The primary outcome was improvement in renal function (estimated glomerular filtration rate [eGFR]) after stenting. Patients were categorized as responders if the eGFR at 30 days or greater after stenting increased by 20% or more compared with before stenting. All others were nonresponders. ResultsThe study cohort included 695 patients with a median follow-up of 7.1 years (interquartile range, 3.7-11.6 years). Based on postoperative change in eGFR, 202 stented patients (29.1%) were responders, and the remainder (n = 493 [70.9%]) were nonresponders. Before RAS, responders had a significantly higher mean serum creatinine, lower mean eGFR, and higher rate of decline of preoperative GFR in the months before stenting. After stenting, responders had a 26.1% increase in eGFR, compared with before stenting (P < .0001), which remained stable during follow-up. In contrast, nonresponders had a progressive 5.5% decrease in eGFR after stenting. Logistic regression analysis identified three predictors of renal function response to stenting: (1) diabetes (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91; P = .013), (2) CKD stages 3b or 4 (OR, 1.80; 95% CI, 1.26-2.57; P = .001), and (3) rate of decline in preoperative eGFR per week before stenting (OR, 1.21; 95% CI, 1.05-1.39; P = .008). CKD stages 3b and 4 and the rate of decline in preoperative eGFR are positive predictors of renal function response to stenting, whereas diabetes is a negative predictor. ConclusionsBased on our data, patients in CKD stages 3b and 4 (eGFR 15-44 mL/min/1.73 m2) are the only subgroups with a significant probability of improved renal function after RAS. The rate of decline of preoperative eGFR over the months before stenting is a powerful discriminator of patients who are most likely to benefit from RAS. Specifically, patients with a more rapid decrease in eGFR before stenting have a significantly greater probability of improved renal function with RAS. In contrast, diabetes is a negative predictor of improved renal function, so interventionalists should be circumspect about RAS in diabetic patients.

Retrieval of renal function after renal artery stenting improves event-free survival in a subgroup analysis of the Cardiovascular Outcomes in Renal Atherosclerotic Lesions trial

ObjectiveThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial with 947 patients, concluded that there was no benefit of renal artery stenting (RAS) over medical therapy. However, patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL trial. CKD is a risk factor for cardiovascular and renal morbidity. We hypothesized that improved renal function after RAS would be associated with increased long-term survival and a lower risk of cardiovascular and renal events in patients with CKD. MethodsThis post hoc analysis of the CORAL trial included 842 patients with CKD stages 2 to 4 at baseline who were randomized to optimal medical therapy alone (OMT; n = 432) or RAS plus OMT (RAS + OMT; n = 410). Patients were categorized as responders or nonresponders based on the change in the estimated glomerular filtration rate (eGFR) from baseline to last follow-up (median, 3.6 years; interquartile range, 2.6-4.6 years). Responders were defined by a 20% or greater increase in eGFR from baseline; all others were designated as nonresponders. Event-free survival was defined as freedom from death and multiple cardiovascular and renal complications. Event-free survival was analyzed using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazards regression analysis was used to identify independent predictors of event-free survival. ResultsThe RAS + OMT group had a higher proportion of patients with improved renal function (≥20% increase in eGFR over baseline), compared with the OMT group (25.6% vs 17.1%; P = .003). However, event-free survival was no different for the two cohorts (P = .18 by the log-rank test). Multivariable Cox proportional hazards regression analysis identified four variables that independently correlated with event-free survival for the stented cohort. Higher preoperative eGFR (hazard ratio, 0.98; 95% confidence interval [CI], 0.96-0.99; P = .002) and being a responder to stenting (hazard ratio, 0.49; 95% CI, 0.26-0.95; P = .033) increased event-free survival, whereas a history of congestive heart failure (hazard ratio, 2.52; 95% CI, 1.46-4.35; P < .001) and a higher preoperative systolic BP (hazard ratio, 1.02; 95% CI, 1.01-1.03; P = .002) decreased event-free survival. Within the stented group, 105 of 410 patients (25.6%) were responders. Event-free survival was superior for responders, compared with nonresponders (P = .009 by log-rank test). The only independent preoperative negative predictor of improved renal function after stenting was diabetes (odds ratio, 0.37; 95% CI, 0.16-0.84; P = .017), which decreased the probability of improved renal function after RAS + OMT. A subset of patients (23.4%) after RAS had worsened renal function, but OMT alone produced an equivalent incidence of worsened renal function. An increased urine albumin/creatinine ratio was an independent predictor of worsened renal function after RAS. ConclusionsCORAL participants who demonstrated improved kidney function after RAS + OMT demonstrated improved event-free survival. This finding reinforces the need for predictors of outcome to guide patient selection for RAS.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Cardiovascular Disease Prevention in Patients With Atherosclerotic Renovascular Disease-Induced Resistant Hypertension: Further Considerations for 24-Hour BloodPressure Profiles.

Abstract 13819: Circulating PON Lactonase Activity Predicts Major Adverse Cardiac Events in Subjects With Atherosclerotic Renal Artery Disease

Introduction: Decreased plasma lactonase activity, catalyzed by high-density lipoprotein (HDL)-associated paraoxonase (PON), is associated with increased oxidant stress and cardiovascular risk in settings such as coronary artery disease as well as some etiologies of chronic kidney disease (CKD). However, whether circulating PON lactonase activity predicts outcomes in atherosclerotic renal artery stenosis (ARAS) is unknown. We sought to determine the prognostic value of circulating PON lactonase activity in subjects with ARAS, particularly in relation to established risk factors. Methods/Results: PON lactonase activity was measured in plasma of subjects with ARAS and either systolic hypertension while taking ≥2 antihypertensive drugs or CKD (n=718) enrolled in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study as well as a cohort of apparently healthy, normotensive non-ARAS subjects (n=33). Participants with ARAS were prospectively followed for incident major adverse cardiac events (MACE, composite of cardiovascular death, nonfatal myocardial infarction, and stroke) over a median follow-up period of 43 months (interquartile range, 31 to 55). PON lactonase activity in ARAS subjects was significantly lower compared with that in non-ARAS control subjects [mean±SD, 2466±839 vs 3514±745 pmol/min/mL, P&lt;0.001]. Next, participants were dichotomized based on the baseline plasma levels of PON lactonase activity, into high (&gt; median) or low (≤ median) groups and were used to predict incident MACE at 3 years. Participants with lower PON lactonase activity had increased MACE at 3 years [67/359 (17%) vs 44/359 (12%), p&lt;0.05]. Lower circulating PON lactonase activity (hazard ratio 1.26, 95% CI 1.0 to 1.53, p=0.016) was a predictor of MACE. After adjusting for traditional risk factors and medication use, lower PON lactonase activity (hazard ratio 1.22, 95% CI 1.01 to 1.50, p=0.04) still conferred an increased risk of MACE. Conclusions: In patients with ARAS, decreased circulating PON lactonase activity, a measure of diminished antioxidant properties of HDL, predicts higher risk of incident long-term adverse cardiovascular events in multivariate models adjusting for established clinical and biochemical risk factors.

Clinical predictors of blood pressure response after renal artery stenting

ObjectiveThe Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial, failed to demonstrate a benefit of renal artery stenting (RAS) over medical therapy in patients with renal artery stenosis and hypertension. However, there are patients for whom RAS is a consideration because of failure of medical therapy. Unfortunately, selection of patients for RAS is complicated by a lack of validated predictors of blood pressure (BP) response. A previous single-center study identified three preoperative markers of BP response to RAS: requirement for four or more antihypertensive medications, preoperative diastolic BP >90 mm Hg, and preoperative clonidine use. To date, these markers of outcome have not been independently validated. The aim of this study was to validate these markers using data from the CORAL trial. MethodsAll patients randomized in the CORAL trial to RAS were included. American Heart Association guidelines were used to categorize patients as BP responders or nonresponders to RAS. BP responders were defined by a postoperative BP <160/90 mm Hg with a reduced number of antihypertensive medications or a reduction in diastolic BP to <90 mm Hg with the same medications after RAS. Patients with stable or worsened BP were labeled nonresponders. Variables associated with a favorable BP response were identified by multivariable logistic regression analysis. ResultsThere were 436 patients who underwent RAS with a median age of 70 years (interquartile range [IQR], 63-76 years). The median systolic and diastolic BPs of the stented cohort at baseline were 149 mm Hg (IQR, 132-164 mm Hg) and 78 mm Hg (IQR, 70-87 mm Hg), respectively. A positive BP response occurred in 284 of 436 (65.1%) stented patients. Multivariable logistic regression analysis identified three independent markers of a positive BP response: requirement for four or more medications (odds ratio, 5.9; P < .001), preoperative diastolic BP >90 mm Hg (odds ratio 13.9; P < .001), and preoperative clonidine use (odds ratio, 4.52; P = .008). The percentage of patients with a positive BP response increased incrementally as the number of markers per patient increased, based on the Cochran-Armitage test for trend (P < .0001). ConclusionsIn patients from the CORAL trial who underwent RAS, the previously reported clinical markers of BP response were validated. A prospective trial to validate their utility as predictors of BP response to RAS is warranted.

Selection of Patients for Angioplasty for Treatment of Atherosclerotic Renovascular Disease: Predicting Responsive Patients

Atherosclerotic renal artery stenosis (ARAS) can cause secondary hypertension, progressive decline in renal function, and cardiac complications. Recent randomized controlled trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study have not reported the benefit of renal artery stenting compared with medical therapy alone to improve renal function or reduce cardiovascular and renal events in the enrolled patients with ARAS. However, observational evidence indicating the benefits of angioplasty in the selected high-risk patients with ARAS has been increasing. Thus, the timely correction of stenosis through angioplasty may have a beneficial effect in selected patients. However, optimal patient selection for angioplasty has been debated and can be challenging at times. Clinicians must identify the responsive patients who would benefit from angioplasty through risk stratification and the prediction of outcomes. Efforts have been made for the determination of predictors that can identify the subgroups of patients who would benefit from angioplasty. Lower age, more severe stenosis, preserved renal perfusion, and absence of diabetes or generalized atherosclerosis have been reported as the predictors for the improvement of hypertension after angioplasty. Global renal ischemia, rapidly declining renal function over 6-12 months, progressive shrinkage of the affected kidney, lower resistive index, and lower levels of albuminuria have been reported as predictors of improved or preserved renal function after angioplasty. This review discusses the identification of ARAS patients who will potentially respond well to angioplasty.

Prediction of cardiovascular outcomes with machine learning techniques: application to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study.

BackgroundData derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study.MethodsWe identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R.ResultsThe best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models.ConclusionPrediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome.Clinical Trial RegistrationClinicalTrials.gov, NCT00081731

Renal Artery Stenosis: New Findings from the CORAL Trial.

The goal of this review is to summarize recent advances in the field and highlight important new insights from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial regarding the optimal management of patients with renal artery stenosis (RAS). The CORAL trial demonstrated that subjects with RAS had similar outcomes whether randomized to optimal medical therapy alone or optimal medical therapy plus renal artery stenting. Subgroup analyses have failed to demonstrate that baseline blood pressure or lesion gradients can predict which subjects may have improved response after stent intervention. Importantly, urine albumin to creatinine ratio appears to different subjects that may benefit from stent intervention versus subjects that are unlikely to achieve any benefit. In addition, there was a trend toward increase benefit in subjects with greater percent stenosis. Atherosclerotic RAS is a frequent finding and is often seen in patients with resistant hypertension, congestive heart failure, chronic kidney disease, and rarely those who need renal replacement therapy. Risk factors for RAS overlap with those of generalized atherosclerosis including hyperlipidemia, smoking, hypertension, and diabetes. Patients with CAD or PVD frequently have co-existing RAS. The management of RAS has been controversial for many years. The CORAL trial provides important insights into the optimal management of subjects with RAS.

Renal Salvage with Renal Artery Stenting Improves Long-term Survival

The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial castdoubt on the benefits of renal artery stenting (RAS). However, the outcomes for patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL Trial. We hypothesized that patients who experienced a significant improvement in renal function after RAS would have improved long-term survival, compared with patients whose renal function was not improved by stenting. This single-center retrospective study included 60 patients with stage 3 or worse CKD and renal artery occlusive disease who were treated with RAS for renal salvage. Patients were categorized as "responders" or "nonresponders" based on postoperative changes in estimated glomerular filtration rate (eGFR) after RAS. "Responders" were those patients with an improvement of at least 20% in eGFR over baseline; all others were categorized as "nonresponders." Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression was used to identify predictors of long-term survival. The median age of the cohort was 66years (interquartile range [IQR], 60-73). Median preoperative eGFR was 34mL/min/1.73m2 (IQR, 24-45). At late follow-up (median 35months, IQR, 22-97months), 16 of 60 patients (26.7%) were categorized as "responders" with a median increase in postoperative eGFR of 40% (IQR, 21-67). Long-term survival was superior for responders, compared with nonresponders (P=0.046 by log-rank test). Cox proportional hazards regression identified improved renal function after RAS as the only significant predictor of increased long-term survival (hazard ratio=0.235, 95% confidence interval = 0.075-0.733; P=0.0126 for improved versus worsened renal function after RAS). Successful salvage of renal function by RAS is associated with improved long-term survival. These data provide an important counter argument to the prior negative clinical trials that found no benefit to RAS.

Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice.

Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

How to manage hypertension with atherosclerotic renal artery stenosis?

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

Approach to atherosclerotic renovascular disease: 2016.

The management of atherosclerotic renal artery stenosis in patients with hypertension or impaired renal function remains a clinical dilemma. The current general consensus, supported by the results of the Angioplasty and Stenting for Renal Atherosclerotic Lesions and Cardiovascular Outcomes for Renal Artery Lesions trials, argues strongly against endovascular intervention in favor of optimal medical management. We discuss the limitations and implications of the contemporary clinical trials and present our approach and formulate clear recommendations to help with the management of patients with atherosclerotic narrowing of the renal artery.

BR 05-2 ANGIOPLASTY OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS

Abstract Atherosclerotic renal artery stenosis is an increasingly recognized medical problem especially in elderly patients. It commonly occurs with systemic manifestations including hypertension (HTN), chronic kidney disease (CKD) or atherosclerotic diseases including coronary or peripheral artery disease. Significant renal artery stenosis may result in HTN, ischemic nephropathy, however it is still in debate about the benefit of revascularization. Although several randomized controlled trials including Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) and Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study has failed to reveal a significant benefit of angioplasty, angioplasty with medical therapy is increasingly accepted in some patients with certain clinical conditions.For determining appropriate candidates for renal artery angioplasty, anatomical evaluation of renal artery stenosis and atherosclerotic change of abdominal aorta should be preferentially undergone. Angiographic stenosis more than 50% with physiologic significance, or ≥70% stenosis is considered significant. Translesional pressure gradient with or without hyperemia should be routinely assessed in intermediate stenosis (50-70%). Intravascular ultrasound assessment may be used to evaluate luminologic severity or characteristics.Global renal ischemia caused by renal artery stenosis should be an appropriate indication of revascularization, however unilateral and solitary ischemia would be considerable. Patients with cardiac disturbance syndrome or pulmonary edema relevant to renal artery stenosis can be managed with renal artery angioplasty. Several prospective randomized trials have failed to show a significant difference in blood pressure (BP) response after revascularization or medical treatment, nevertheless resistant HTN with global renal ischemia would be a proper indication of revascularization. Both patient groups with revascularization and medication alone in CORAL showed similar BP response about 15 mmHg. Such BP responders with optimal medication may be not appropriate candidates for revascularization for controlling BP. Patients with reduced renal function and global renal ischemia may be also good candidates for renal artery stenting. However, evidences to support revascularization in unilateral renal artery stenosis are limited. Revascularization would be considered if renal artery stenosis is relevant to hemodynamic significance. Although revascularization with stenting have been commonly used for patients with renal artery stenosis, previous results are inconclusive and lacking to support comprehensive indications of current clinical application. Selection of candidates who benefits with angioplasty should be carefully conducted with sufficient diagnostic evaluation.

An alternative empirical likelihood method in missing response problems and causal inference.

Missing responses are common problems in medical, social, and economic studies. When responses are missing at random, a complete case data analysis may result in biases. A popular debias method is inverse probability weighting proposed by Horvitz and Thompson. To improve efficiency, Robins et al. proposed an augmented inverse probability weighting method. The augmented inverse probability weighting estimator has a double-robustness property and achieves the semiparametric efficiency lower bound when the regression model and propensity score model are both correctly specified. In this paper, we introduce an empirical likelihood-based estimator as an alternative to Qin and Zhang (2007). Our proposed estimator is also doubly robust and locally efficient. Simulation results show that the proposed estimator has better performance when the propensity score is correctly modeled. Moreover, the proposed method can be applied in the estimation of average treatment effect in observational causal inferences. Finally, we apply our method to an observational study of smoking, using data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions clinical trial. Copyright © 2016 John Wiley & Sons, Ltd.

Endovascular Treatment of Renal Artery Stenosis in the Post CORAL Era.

Atherosclerotic renal artery stenosis (RAS) is highly associated with hypertension and renal insufficiency. Determining causation and who may benefit from RAS treatment remains difficult. The role of endovascular management of atherosclerotic RAS was challenged by several recent randomized controlled trials (RCT) which failed to demonstrate benefit of stenting. In the largest RCT to date, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study did not find benefit of revascularization compared to medical therapy alone. While such RCTs represent the highest level of evidence to date, the conclusions drawn from them should be interpreted with caution due to substantial flaws in study design, inclusion, and exclusion criteria. The current AHA/ACC recommendations for RAS management are supported by many level-II evidence cohort studies which consistently found benefit of revascularization in groups with the highest likelihood of clinically significant RAS. Further study of these patient groups are needed to define a clear role for endovascular therapy of renal artery stenosis.

Renal Artery Stent Outcomes: Effect of Baseline Blood Pressure, Stenosis Severity, and Translesion Pressure Gradient

BackgroundMultiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. ObjectivesThe study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. MethodsUsing data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. ResultsThere were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. ConclusionsBased on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the trans-stenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731)

Abstract 17358: Stenting of Atherosclerotic Renal Artery Stenosis Does Not Prevent Congestive Heart Failure, an Analysis of the Coral Trial

Introduction: In current guidelines congestive heart failure (CHF) is an indication for renal artery stenting, however there is no data on the utility of stenting for the prevention of CHF. We sought to determine the effect of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) without a history of CHF. Hypothesis: In ARAS renal artery stenting does not prevent incident CHF in patients with no history of CHF. Design and method: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial is a prospective, international, multicenter clinical trial that randomized participants with ARAS, who received optimal medical therapy plus stenting versus no stenting. Optimal medical therapy included treating blood pressure and diabetes to goal, use of an angiotensin receptor-blocking drug, statin, and anti-platelet therapy. Glomerular filtration (eGFR) was estimated using the MDRD-GFR equation. Patients were followed for a median of 43 months (IQR, 31 to 55). Results: At enrollment, there were 795 out of 931 patients without a history of CHF, 395 were in the medical therapy group and 400 were in the medical therapy plus stenting group. In this group 117/795 had global renal ischemia. The rate of CHF admission (7% vs. 6%. p=0.74) and the pulmonary edema rate within those admitted for CHF were not different (82% vs. 64%, p=0.21). The rate of incident CHF was not different in patients with global renal ischemia and renal stenting did not prevent CHF events in this subgroup. Neither the composite event rate (35% vs. 34%, p=0.72), nor the rate of cardiovascular death (8% vs. 8%, p=0.96) differed between the two groups. At 3-year follow-up no differences were observed between medical therapy and medical therapy plus stenting for systolic blood pressure (SBP) (135±19 vs. 134±21 mmHg, p=0.74) or eGFR (56±22 vs. 55±23 ml/min, p=0.50). Conclusions: Renal artery stenting and optimal medical therapy, when compared to optimal medical therapy only, did not reduce the risk of CHF, or other cardio-renal events in patients that were enrolled without history of CHF in the CORAL trial.

Regional and physician specialty–associated variations in the medical management of atherosclerotic renal–artery stenosis

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti–hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin–converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal–artery stenosis.