Clinical Outcomes
There was no significant difference in the occurrence of the primary composite end point between the stent group and medical therapy–only group (35.1% and 35.8%, respectively; hazard ratio, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58) (Table 2TABLE 2
Clinical End Points.
and Figure 2FIGURE 2
Kaplan–Meier Curves for the Primary Outcome.
). In addition, no significant between-group differences were observed in the rates of the components of the primary end point (Table 2, and Fig. S1 through S6 in the Supplementary Appendix). We also observed no significant difference in all-cause mortality during the follow-up period (Table 2).
No interactions were observed between treatment and the four prespecified subgroups — those defined according to sex, race (black vs. others), presence or absence of global ischemia, and presence or absence of diabetes — with respect to the occurrence of a primary end-point event (Figure 3FIGURE 3
Forest Plot of Treatment Effects within Subgroups.
). In addition, no significant differences in the treatment effect were observed in other subgroups.
Blood Pressure over Time
At baseline, participants were taking a mean of 2.1±1.6 antihypertensive medications. At the end of the study, the number of medications increased in both the stent group and the medical therapy–only group but did not differ significantly between the two groups (3.3±1.5 and 3.5±1.4 medications, respectively; P=0.24). Systolic blood pressure declined in both the medical therapy–only group (by 15.6±25.8 mm Hg) and the stent group (by 16.6±21.2 mm Hg). In the longitudinal analysis, the systolic blood pressure was modestly lower in the stent group than in the medical therapy–only group (−2.3 mm Hg; 95% CI, −4.4 to −0.2 mm Hg; P=0.03), and the difference persisted throughout the follow-up period (Fig. S7 in the Supplementary Appendix).
DISCUSSION
The CORAL trial was designed to test whether renal-artery stenting, when added to protocol-driven contemporary medical therapy, improves clinical outcomes in persons with atherosclerotic renal-artery stenosis. We found no benefit of stenting with respect to the rate of the composite primary end point or any of its individual components, including death from cardiovascular or renal causes, stroke, myocardial infarction, congestive heart failure, progressive renal insufficiency, and the need for renal-replacement therapy. This result was consistent across all prespecified subgroups, including patients with global renal ischemia and patients with other high-risk characteristics. We did observe a modest, but statistically significant, reduction of 2 mm Hg in systolic blood pressure with stenting, but this reduction did not translate into a reduction in clinical events.
Other randomized trials, including the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial15 and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) trial,16 assessed the usefulness of renal-artery stenting with respect to kidney function and showed no significant difference in this key measure. These studies have been criticized for enrolling some participants who did not have clinically significant renal-artery stenosis and for not having their findings confirmed by core laboratories.21 In addition, none of the previous studies were designed specifically to detect a benefit with respect to clinical events. We sought to address these concerns in CORAL.
A key issue in the interpretation of our results is whether the medical therapy that was given to CORAL participants can be replicated in clinical practice. The medical therapy in our study included the use of an angiotensin-receptor blocker, with or without a thiazide-type diuretic, with the addition of amlodipine for blood-pressure control. In addition, participants received antiplatelet therapy and atorvastatin for management of lipid levels, and diabetes was managed according to clinical practice guidelines.19,20 With this regimen, patients who received medical treatment alone had remarkably good cardiovascular and renal outcomes, despite their advanced age and the high rates of hypertension, diabetes, chronic kidney disease, and other coexisting cardiovascular conditions.
Renal-artery stenting remains a common procedure in current clinical practice. The CORAL study shows that, when added to a background of high-quality medical therapy, contemporary renal-artery stenting provides no incremental benefit. From this result, it is clear that medical therapy without stenting is the preferred management strategy for the majority of people with atherosclerotic renal-artery stenosis.
The CORAL trial had some limitations. First, patients could be enrolled in the trial with renal-artery stenosis of 60% or more, and there is debate about the severity of stenosis that is necessary to justify intervention.22 However, we were unable to show a benefit among participants with renal-artery stenosis of more than 80%, as measured by the enrolling investigators. Second, we did not include patients with fibromuscular dysplasia, and several studies suggest that angioplasty alone may improve blood-pressure control and even cure hypertension in young persons.23 Third, although the inclusion criteria for CORAL were intentionally broad, some patients who were screened and deemed to be eligible were not enrolled in the trial, including patients who were not enrolled because of the preference of their physician. Some of these patients may have been treated by means of stenting by physicians who were convinced of the clinical benefit of the procedure. Nonetheless, the baseline clinical and angiographic characteristics of the study population, as well as the response with respect to systolic blood pressure, were remarkably similar to those in patients enrolled in previous single-group, FDA-approval trials of renal stents.24-26
In summary, renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease.