Meta-analysis: Renal Intervention Reduces BP Drugs, Not Outcomes

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Patients with renal artery stenosis who receive percutaneous revascularization on top of medical management may need fewer antihypertensive medications after treatment. But they derive no clinical benefits over nearly 3 years of follow-up compared with those who receive medical therapy alone, according to a meta-analysis published exclusively online by the American Heart Journal in March 2011.

Researchers led by Samir R. Kapadia, MD, of the Cleveland Clinic (Cleveland, OH), compiled data from 6 randomized trials that compared percutaneous revascularization with or without medical management in patients (n =1,208) with significant renal artery stenosis (≥ 50%). The studies conducted before 2001 (EMMA, SNRASCG, and DRASTIC) enrolled fewer than 50 patients each and involved balloon angioplasty. The remaining trials (ASTRAL, STAR, and NITER) were all published in 2009 and assessed primarily renal stenting. Overall, the mean number of hypertensive medications at baseline was 2.74 and 2.76 in the percutaneous intervention and medical therapy groups, respectively (P = 0.76).

Mixed Bag

In addition to differences in revascularization technique, much variation was observed among the trial populations. The prevalence of bilateral stenosis varied widely, from 0 in EMMA to 54% in ASTRAL. The STAR trial included only patients with chronic renal insufficiency, whereas EMMA enrolled only those with resistant hypertension.

Moreover, crossover between treatment groups within trials was common. For example, 28% and 20% of patients in the revascularization arms of STAR and ASTRAL did not undergo their assigned therapy, mainly due to disagreement between noninvasive and invasive assessments of stenosis severity. On the other hand, a full 44% of patients in DRASTIC and 27% in EMMA who were originally assigned to medical therapy alone wound up undergoing revascularization.

After a mean follow-up of 29 months, patients randomized to undergo revascularization saw no changes in blood pressure or serum creatinine from baseline, but they did require fewer antihypertensive medications (table 1).

Table 1. Revascularization Group: Follow-up vs. Baseline

Abbreviations: BP, blood pressure.

^a P < 0.001.

Nor did percutaneous revascularization improve clinical outcomes compared with medical therapy alone (table 2).

Table 2. Clinical Outcomes: Revascularization vs. Medical Therapy Alone

Abbreviations: CHF, congestive heart failure.

There was no evidence of heterogeneity among the studies for any of the endpoints.

The small reduction in need for antihypertensive drugs by the end of follow-up “might indicate an incremental blood pressure-lowering benefit with percutaneous revascularization,” the investigators conclude, adding that the results confirm an earlier meta-analysis of balloon angioplasty vs. medical management. “Because percutaneous angioplasty with stenting has been shown to be superior to balloon angioplasty alone, our analysis further builds on the study and adds further insights into clinical endpoints including all-cause mortality, CHR, stroke, and worsening renal failure.”

But the researchers’ power calculations found that nearly 6,000 patients are necessary to detect a significant difference in the composite of death, congestive heart failure, and stroke, while almost 28,000 would be required to detect disparities in worsening renal function with 80% power. “These calculations suggest that such a large trial may never be performed,” they write, adding that 2 randomized controlled trials comparing revascularization and medical management in patients with renal artery stenosis—RAS-CAD and CORAL—are ongoing. These trials may provide some answers, they say, even though the largest plans to enroll only 1,080 patients.

In the meantime, Dr. Kapadia and colleagues advise, the “current study and recent trials need to be considered at the time of formulation of the new guidelines on this topic.”

Barriers to Stenting Benefit

Several factors may explain the lack of benefit for renal function or clinical outcomes, the investigators explain. For one, the risk factors associated with aortorenal vascular disease and parenchymal kidney disease overlap considerably, such that several of the conditions that can result in atherosclerotic narrowing in the renal arteries, including diabetes, smoking, dyslipidemia, and hypertension, are also independently associated with direct renal injury. Kidney function may in fact be mediated by underlying microvascular kidney disease rather than macroatherosclerotic renal artery stenosis, they note.

In addition, the researchers point out, “long-standing [renal artery stenosis] results in activation of inflammatory and profibrogenic pathways, production of reactive oxygen species leading to oxidative stress, and sympathetic nerve activation. These can all perpetuate irreversible glomerular damage with time, and thus, restoring renal artery perfusion in these situations may no longer produce meaningful recovery function.”

Specific to stenting, there can be procedural complications such as distal embolization and contrast-induced kidney injury. “Furthermore, there may be some impact of exposing the kidneys to high blood pressure with stenting, which nullifies any potential benefit,” the investigators note. “It is thus unknown if aggressive control of blood pressure in the poststenting part and close surveillance for restenosis would change outcomes after percutaneous revascularization.”

Moreover, medical management of renal artery disease has substantially improved in recent years, with ACE inhibitors, angiotensin-II receptor blockers, and statins all showing signs of efficacy. “The incremental benefit in blood pressure with percutaneous revascularization noted in our study could thus potentially be matched by optimal use of the above medications,” Dr. Kapadia and colleagues conclude.

Source:

Kumbhani DJ, Bavry AA, Harvey JE, et al. Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: A meta-analysis of randomized controlled trials. Am Heart J. 2011;161:622-630.e1.

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