Measuring Response to Renal Denervation Depends on BP Decline, Clinical Relevance

San Francisco, CA—Blood pressure (BP) remains the appropriate endpoint to measure response to renal denervation therapies, but the extent of the decline necessary to qualify as clinically relevant will continue to be the subject of debate, according to a presenter at TCT 2013.

Although office BP should continue to be the primary assessment method, other options exist, said Krishna
Rocha-Singh, MD, of Prairie Heart Institute at St. John’s Hospital in Springfield, Ill.

“Any measurement that safely, reproducibly and adequately performs the measurement should be considered, whether it be home BP assessment or ambulatory BP assessment,” Rocha-Singh said.

The question of clinical relevancy

The debate about what qualifies as a clinically relevant BP response to renal denervation therapies centers on several key questions, Rocha-Singh said.

They include:

• Does the definition differ between drug trials and device trials?
• What BP assessment options exist to determine relevance?
• What do payers consider relevant, and will relevance have to be tied to cost savings for them?

“These are the issues we need to start thinking about as trialists,” Rocha-Singh said.

He cited prior studies that helped define clinically relevant BP reductions such as:

• A 10 mm Hg reduction in systolic BP is associated with a 22% reduction in MI and a 41% reduction in cerebrovascular accidents.
• Each 5 mm Hg reduction in systolic BP leads to a 13% risk reduction in composite CV events, including MI, cerebrovascular accidents, congestive HF and CV death.
• Vascular mortality is reduced by half when systolic BP is 120 mm Hg instead of 140 mm Hg.

“Ten mm Hg is arguably the de facto high bar, but it is the de facto high bar in severe treatment-resistant hypertension,” Rocha-Singh said. “We have to change the definition as we move into moderate hypertension; if we don’t, it could theoretically end up in a moderate hypertension trial that we could have a lot of nonresponders who also get to the goal.”

Ambulatory BP provides a more complete assessment of BP values over a 24-hour period, provides an evaluation of BP variability and results in considerably less bias than office readings, combining to better predict hypertension-related CV events, Rocha-Singh said.

“More importantly, as you start reducing the value of BP, there’s more congruence between ambulatory and office BP,” he said.

Addressing noncompliance

Efforts also must be made to minimize patterns of noncompliance.

“We have to understand the human factor, and we have to understand persistence,” Rocha-Singh said. “Through the time of our studies, these become very, very important variables, and if we do not control for them, they will impact our endpoints. Persistence and adherence have to enter our vocabulary.”

The question remains whether it is necessary to conduct a 5-year, 5,000-patient trial to compare best medical therapy plus renal denervation vs. best medical therapy alone.

“I ask the question: What’s going to happen during those 5 years with regard to technologies, and how do you put in people who drop in and out of the medical regimen?” Rocha-Singh asked.

Disclosures:

Rocha-Singh received consultant fees/honoraria from several device manufacturers; has a founding/ownership role with Convergence LLC; and has a board role with VIVA.