Initial results of a landmark clinical trial sponsored by the National Institutes of Health could settle a long-running debate about target blood pressure levels and how aggressive blood pressure management should be.

The NIH experts cautioned reporters during a Friday press conference that the results of the SPRINT (Systolic Blood Pressure Intervention Trial) study are preliminary, but they said the data could have a significant impact on guidelines regarding hypertension treatment. The intervention in the trial, which adjusted the amount or type of blood pressure medication to achieve a target systolic pressure of 120 millimeters of mercury (MM Hg), reduced rates of cardiovascular events by almost a third and the risk of death by almost a quarter, as compared to the commonly recommended target of 140 mm Hg.

The SPRINT study, which began enrolling patients in 2010 with a $14.7 million NIH grant, included more than 9,300 participants age 50 and older throughout the U.S. and Puerto Rico. The average patient enrolled in the study had a blood pressure of 140/90 and were not being treated for hypertension. It is the largest study of its kind, the NIH said, and the organization stopped the study a full year earlier than expected after seeing the initial data.

"We have these very strong preliminary results that are going to be further analyzed and a primary outcomes paper will be published by the end of this year that will be of great interest to physicians," said Lawrence Fine, chief of the clinical applications and prevention branch at the National Heart, Lung, and Blood Institute (NHLBI), the primary sponsor of SPRINT.

NHLBI Director Gary Gibbons said the study provides "potentially lifesaving information" that will help providers determine the best treatment options for some of their patients, particularly those over age 50.

Gibbons said there has been "considerable uncertainty" regarding the amount and type of pressure medication that should be used to achieve an ideal systolic pressure level. The SPRINT results have the potential to benefit a portion of the estimated one in three adults in the United States who have high blood pressure, he said.

Principal Investigator Jackson Wright of Case Western Reserve University School of Medicine (Cleveland) said the SPRINT study population was diverse and included women, racial/ethnic minorities, and the elderly. He said the study did not include patients with diabetes, prior stroke or polycystic kidney disease.

Wright also noted that other elements of the trial are ongoing, including a sub-study examining the impact of a lower blood pressure target on the incidence of dementia and the decline of cognitive function.

"Safety data from SPRINT are still being analyzed and will be looked at closely," Wright said. "The first look indicates that the treatment is well tolerated in the lower blood pressure group."

All of the data still needs to be peer-reviewed and published to be verified by other experts, he said. "At that point, the data will be digested from SPRINT by the providers as well as the various guidelines panels."

Principal Investigator Suzanne Oparil of the University of Alabama, Birmingham said patients in the intensive treatment group required three or more drugs to achieve the target of 140 mm Hg and because many patients did not tolerate some of the drugs, investigators used a broad spectrum of medication choices with respect to the major drug classifications. She emphasized, however, that the trial was not designed to compare one drug to another but rather the outcomes related to the lower blood pressure target.

"Current recommendations for what level of blood pressure to attain when treating hypertension are not consistent," Oparil said.

That's why the SPRINT results have the potential to significantly change the standard for managing high blood pressure, she said. "We strongly believe that this is a very important study to address that controversy, but that's the future work of guidelines groups."

Currently, the recommended goal for people over age 60 who do not have diabetes or chronic kidney disease is 150 mm Hg or lower while the target is less than 140 mm Hg for younger patients. "A number of committee members concluded the goals should be 140 mm Hg so in all these cases, if the SPRINT findings are consistent with what we believe now, the 140 mm Hg goal will be challenged too," Oparil said.

When pressed by reporters for a consumer message regarding the data, the NIH experts and the investigators emphasized that the findings are preliminary and should not lead any patient to either increase or stop any of their medications on their own.

"Our results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall," Fine said. "But patients should talk to their doctor to determine whether this lower goal is best for their individual care."

Renal Denervation Not Dead

While SPRINT focused on the ideal blood pressure level and participants were treated with drug therapy, the findings may revive enthusiasm for renal denervation, a technique that involves ablation of nerve endings in the renal artery as a solution for uncontrolled high blood pressure.

A couple years ago device companies were racing to bring renal denervation to the market but most dropped out of the running after Medtronic's (Dublin) SYMPLICITY HTN-3 trial failed to demonstrate efficacy in lowering blood pressure against a sham control group of patients (Medical Device Daily, Jan. 10, 2014).

Medtronic and several others re-entered the renal denervation race earlier this year. In April, Medtronic launched a new program, SPYRAL HTN, that includes two global studies designed to address the confounding factors encountered in the SYMPLICITY HTN-3 trial, including medication, patient population, and procedural variability (MDD, April 2, 2015).

Physicians in both studies of the new SPYRAL HTN program will perform renal denervation with Medtronic's technology, composed of the multi-electrode Symplicity Spyral catheter and Symplicity G3 radiofrequency generator. The trials are being conducted simultaneously at about 20 centers worldwide to investigate the impact of renal denervation both in the absence of and in the presence of antihypertensive medications.

The SPYRAL HTN-ON MED study requires patients who, despite use of drugs from three of the most common classes of hypertension medication, do not achieve adequate blood pressure control. These drugs are not required to be prescribed at maximum tolerated dosages, a factor that may have contributed to variability in patient adherence and the large number of medication changes during the SYMPLICITY HTN-3 trial, Medtronic said. The company also said medication adherence will be closely monitored and there will be a focus on ambulatory blood pressure monitoring to ensure consistency between both arms of the on- and off-medication studies.

Other companies that either stayed in or re-entered the renal denervation race include Boston Scientific (Marlborough, Mass.) and Recor Medical (Palo Alto, Calif.).

For Boston Scientific, the REINFORCE trial is designed to mimic a pharmacology clinical trial to answer the question if renal denervation reduces blood pressure for hypertension. The U.S.-only proof of concept study includes 15 centers and is designed to fulfill requirements for an FDA Phase II investigational device exemption. The trial includes a two-to-one randomization between treatment with the company's Vessix device and a masked procedure where patients will be given a renal angiogram with no active therapy. Patients will be medication-free with a four week wash-out period to be confirmed by a urine test.

Recor said in April it had met with the FDA regarding a new randomized controlled trial of its Paradise renal denervation system in hypertensive patients in the absence of drug therapy. The company plans to conduct the new study at 20 to 25 sites in the U.S. and Europe.

Recor has a different kind of horse in the renal denervation race because its Paradise device is a water-cooled, expandable balloon enveloping a central ultrasound technology designed to generate a uniform ablation with a distinctive penetration. //