SYMPLICITY HTN-3 Substudy Examines BP Response Factors in African Americans

African American patients enrolled in the SYMPLICITY HTN-3 trial derived an almost identical magnitude of systolic BP reduction regardless of whether they received renal denervation or the sham procedure. New research presented at TCT 2014 suggests these responses appear to be related to post-randomization interaction with an exposure that impacted BP.

Investigators led by John M. Flack, MD, PhD, of Wayne State University, Detroit, stratified the 535 patients who were randomized to renal denervation or sham procedure by African American or non-African American status. Approximately 64.3% of African American patients received renal denervation compared with 67.7% of non-African American patients.

While non-African American patients treated with renal denervation were more likely to see a reduction in office systolic BP at 6 months compared with those who had a sham procedure, the same was not true for their African American counterparts (see Figure).

A Salt sensitivity risk analysis further confirmed that the only significant difference in change in office systolic BP between treatment and sham procedure groups at 6 months was seen among high-risk non-African Americans (-19.9 vs. -0.7 mm Hg; P<.001).

Searching for Answers 

Flack referenced the five factors that influence medication adherence (social support and insurance coverage) and nonadherence (complexity of therapy, depression and younger age) as demonstrated in the FOCUS trial. “By definition, [renal denervation] is a complex therapy,” he noted.

In patients who were prescribed at least one medication taken at least three times a day, a much greater response in office systolic BP was seen in the renal denervation vs. sham group in both African American (P=.2) and non-African American patients (P=.019). Furthermore, non-African American patients treated with renal denervation reported about a 6-mm Hg better office systolic BP reduction than controls whether (P=.05) or not (P=.06) they were prescribed aldosterone antagonists. However, the same pattern was not seen in African Americans.

Citing commonly discussed limitations of SYMPLICITY HTN-3, Flack highlighted the small sample size, unquantified pharmacological adherence, some speculative interpretation, and no measurement of dietary sodium intake.

“The case for aggressive blood pressure control in African Americans, even to levels below conventional blood pressure targets, has previously been made,” he concluded. “However, the unbiased renal denervation therapy effect in African Americans with uncontrolled hypertension still remains to be elucidated. Importantly, our results also suggest that attention to limiting post-[renal denervation] plasma volume expansion might also benefit non-African Americans as well.”

In an online discussion, digital moderator William A. Gray, MD, of Columbia University Medical Center in New York, said “we should be thinking twice about [renal denervation]” in any patient when medication compliance is uncertain.

At baseline, African American patients had higher office diastolic BP ambulatory systolic and diastolic BP and BMI, and were younger, more often women and more likely to have a history of CAD, stroke or heart failure than non-African Americans. They were also typically prescribed more antihypertensive drugs and vasodilators and fewer aldosterone antagonists and angiotensin receptor blockers.

Disclosures: 

• Flack reports receiving grant funding from Medtronic, the National Institutes of Health and Novartis and consulting for Back Beat Hypertension, Medtronic and Novartis.