Reed Miller

May 10, 2011

May 6, 2011 (Baltimore, Maryland) — The HERCULES trial met its primary end point of reduced blood pressure with renal stenting, yet the study was "disappointingly negative," according to author Dr Michael Jaff (Massachusetts General Hospital, Boston), because it also showed that brain natriuretic peptide (BNP) levels are not a good predictor of which hypertensive patients benefit most from this therapy.

HERCULES trial is a prospective, multicenter, nonrandomized trial of renal stenting with the RX Herculink Elite renal stent (Abbott Vascular) in patients with atherosclerotic renal artery stenosis and uncontrolled hypertension. The trial is also the largest-ever prospective series evaluating the role of BNP as a predictor of systolic blood pressure response following renal artery stenting, according to Jaff, who presented the results of the trial here at the Society for Cardiovascular Angiography and Interventions 2011 Scientific Sessions.

In two previous studies, Dr Thomas Zeller (University Hospital Basel, Switzerland) et al [1] and Dr Jose Antonio Silva (Ochsner Clinic, Slidell, LA) et al [2] suggested that baseline and elevated BNP levels may predict a significant blood-pressure response following renal artery stenting, "which would be of great value in predicting who would benefit from renal artery stenting," Jaff said.

All of the patients in the study had significant hypertension, with a baseline blood pressure greater than 140/90 mm Hg, were on two antihypertensive medications, and had failed balloon renal angioplasty. In the 202 treated patients, a total of 241 renal artery lesions, including 39 bilateral lesions, were stented. The primary end point was nine-month binary restenosis as determined by duplex ultrasound and/or angiographic analysis, with a performance goal of 28.6%. The investigators also measured changes in blood pressure, antihypertensive medications, and renal function between baseline and nine months, as well BNP levels at 24 hours and 30 days postprocedure.

Although there was no change in the use of ACE inhibitors, angiotensin II receptor blockers, or diuretics in the study population, the trial met the primary end point, with a restenosis rate of 10.5% at nine months. The study device, procedure, and clinical success rates were 96.0%, 99.2%, and 98.0%, respectively. Freedom from major adverse events and reintervention was 94.8%.

Systolic blood pressure significantly decreased from a mean of 162 mm Hg before the procedure to 145 mm Hg after nine months (p<0.0001). However, despite the reduction in systolic blood pressure, mean BNP levels remained elevated at one month. A BNP of >80 pg/mL indicates the onset of heart failure. Two-thirds of the patients in HERCULES had a BNP >80. BNP dropped from an average of 181 to 154 pg/mL (p=0.01), with no evidence of a statistical correlation between BNP levels at baseline and systolic blood pressure reduction or between BNP reduction and blood-pressure response.

Jaff suggested that the ongoing CORAL trial, comparing medical therapy plus renal stenting with medical therapy alone in patients with systolic hypertension and renal artery stenosis, might find a subset of patients in whom BNP is a helpful biomarker, but "clearly, in this scenario, where we chose real patients with real hypertension, it didn't look like it helped at all.

"There are also other biomarkers that have been teased out in the literature that may show promise to find any data that help us to predict benefit--maybe markers during the initial arteriogram like fractional flow reserve or pressure gradients. But this field is struggling for help, and unfortunately we weren't able to provide predictive help," Jaff said.

HERCULES was sponsored by Abbott. Jaff is a nonpaid consultant to Abbott.