Brain Natriuretic Peptide Did Not Predict Blood Pressure Outcomes After Renal Artery Stenting in HERCULES

May 5, 2011—The Society for Cardiovascular Angiography & Interventions (SCAI) announced findings from the HERCULES trial showed that brain natriuretic peptide (BNP), which is associated with congestive heart failure and renal failure, is not predictive of reduction in systolic blood pressure (BP) in patients treated with renal artery stenting. Michael R. Jaff, DO, presented the HERCULES data at the SCAI 2011 scientific session in Baltimore, Maryland.

According to SCAI, the HERCULES study is a prospective, multicenter trial of renal stenting in patients with atherosclerotic renal artery stenosis with uncontrolled hypertension evaluating the safety and effectiveness of the RX Herculink Elite renal stent system (Abbott Vascular, Santa Clara, CA). The investigators noted that atherosclerotic renal artery stenosis accelerates hypertension and threatens renal function.

The study reviewed outcomes for 202 patients (241 lesions) with uncontrolled hypertension who were treated with a renal artery stent between August 2007 and October 2009. The primary endpoint was the 9-month restenosis rate, and secondary endpoints included changes in BP, antihypertensive medications, renal function, and the predictive value of BNP.

The investigators hypothesized that BNP could be useful in predicting outcomes in patients with uncontrolled hypertension who are treated with renal artery stenting. BNP is secreted in the heart in response to excessive stretching of the heart muscle cells. Its name was derived from its first discovery in the brain of pigs, but in humans it is produced mainly in the heart. Currently, BNP is useful in diagnosing and monitoring patients with congestive heart failure.

The background of the hypothesis is that in one small series of patients with hypertension and renal artery blockage, patients with high BNP levels (> 80 pg/mL) had impressive reductions in blood pressure compared to patients whose baseline BNP levels were not elevated, which was reported by Jose A. Silva, MD, et al in Circulation (2005;111:328–333). A subsequent larger series of 120 patients reported by Daniel Staub, MD, et al in the European Journal of Vascular and Endovascular Surgery suggested that the baseline BNP of > 50 pg/mL was predictive of clinical improvements in blood pressure in 79% of patients (2010;40:599–607).

Dr. Jaff reported that the primary endpoint of the HERCULES study was met. Results for the secondary endpoints showed systolic BP decreased significantly after stenting with no change in medication requirements, but mean BNP levels remained elevated after 1 month. The study found no evidence of a correlation between elevated pretreatment BNP levels and systolic BP reduction at follow-up. The investigators measured BNP before treatment, at 24 hours, and at 30 days.

The investigators found that 66% of patients had BNP > 80 pg/mL. Baseline serum creatinine was 1.2 ± 0.4, and 61.5% of subjects had an estimated glomerular filtration rate (eGFR) < 60. eGFR was stable at 9 months. There was a reduction in mean systolic BP, but mean BNP levels remained elevated at 1 month. There was no evidence of a correlation between BNP levels at baseline and systolic BP reduction, nor between BNP reduction and systolic BP response. The primary endpoint was met with a 9-month restenosis rate of 10.5% (P < .0001), which was significantly lower than the performance goal of 28.6%. The study device, procedure, and clinical success rates were 96%, 99.2%, and 98%, respectively. The rate of freedom from major adverse events and reintervention was 94.8%.

The HERCULES investigators concluded the trial demonstrated clinically and statistically significant systolic BP reduction in patients with multidrug uncontrolled hypertension associated with low in-stent restenosis and complication rates but that elevated pretreatment BNP levels were not predictive of reduction in systolic BP. Further studies of predictors of systolic BP response after renal artery stenting are needed, the investigators advised.

“The clinical results are promising, as we found very low restenosis rates and a significant drop in blood pressure following renal artery stenting,” commented Dr. Jaff. “One goal of the study was to identify a means to predict which patients will have the best outcome after renal artery stenting. No correlation was found between pretreatment BNP levels and systolic BP response, and patients with the best results did not have a significant reduction in BNP levels, so our results show the search must continue for the best means to predict how patients will fare after renal artery stenting.”