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Implanted Baroreflex Activation Device Fails Trial's Goals

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Results Leave Unanswered Efficacy Questions

The results from this study leave many questions unanswered about the efficacy of this approach to treating persistent, treatment-resistant hypertension.

Patients enrolled in the study should have been thoroughly assessed for neuroendocrine hypertension. About a third of patients with treatment-resistant hypertension have a neuroendocrine cause.


Dr. Prakash C. Deedwania

The study’s design also left unclear how many enrolled patients were truly treatment resistant. One month on stable treatment with at least three drugs may not identify patients who are unresponsive to drugs, as some drugs, such as the direct renin inhibitor aliskiren, take longer than 1 month to start having a complete effect. In addition, current hypertension treatment guidelines from the American Heart Association call for using a mineralocorticoid receptor antagonist such as spironolactone or amiloride in patients with persistent hypertension that remains unresponsive to combinations of other drugs (Hypertension 2008;51:1403-19). The current report gives no information on whether all enrolled patients had first received spironolactone, a very inexpensive drug that often works in otherwise unresponsive patients.

I participated in research several years ago that tested baroreflex activation as a treatment for refractory angina. This approach did not pan out because, while the treatment showed initial efficacy, the effect declined over the longer term.

In my opinion, renal artery denervation is, for now, a more proven, novel way to manage patients with hypertension that is truly drug resistant. Carotid baroreflex activation will require more study and better evidence before we can consider it a new option for these patients.

Dr. Prakash C. Deedwania is professor of medicine with the University of California, San Francisco, in Fresno. He said that he has no disclosures.


 

FROM THE ANNUAL MEETING OF THE AMERICAN COLLEGE OF CARDIOLOGY

One end point assessed short-term response after 6 months, defining success as at least a 10-mm Hg drop in systolic pressure, compared with baseline. This criteria for success occurred in 54% of patients with an activated device in the study’s first 6 months and in 46% of those with an inactive device, an 8% difference in response rate between the active and control arms that failed to meet the prespecified goal of a 20% difference. Dr. Bisognano speculated that the placebo response may have been so high because of continued drug treatment optimization during this period.

The second end point assessed the 12-month response in all 265 patients, again using a 10-mm Hg drop in systolic pressure relative to baseline as the criterion for a positive response. This reduction occurred in 88% of patients, surpassing the prespecified success threshold of 65%.

The third end point focused on 30-day safety. The 25% of patients with an adverse event exceeded the prespecified threshold of 18%.

The fourth end point looked at safety at 6 months, with an adverse-event threshold in the active-treatment arm of no more than 15% greater than in the control arm. The results showed that patients receiving activation had a 2% reduced rate of adverse events, compared with the inactive, control arm, which meant the results fulfilled this criterion of success.

The fifth end point looked at the overall adverse event rate on active therapy in all 265 patients after 12 months. The 13% actual rate fell within the prespecified goal of less than 28%, meaning the results fulfilled this criterion of success.

The study also assessed efficacy another way, by tallying the percentage of patients whose systolic pressure dropped below 140 mm Hg. At the 6-month mark, this degree of blood pressure reduction occurred in 42% of patients receiving activation and in 24% of patients whose device had not yet been activated, a statistically significant difference. At the 12-month mark, 53% of the patients on continuous active treatment and 51% of those who switched from 6 months off treatment to 6 months on treatment reached this systolic pressure goal.

In addition, the study included an echocardiography substudy designed to assess the impact of baroreflex activation on left ventricular mass and shape. At baseline, these 60 patients had an average left ventricular mass index of 117 kg/m2. A year later, the average had dropped to 102 kg/m2, a statistically significant difference. Patients also shifted toward having more normalized left ventricular shapes, Dr. Bisognano reported in a separate talk at the meeting.

Dr. Bisognano said that he has received consulting fees or honoraria from CVrx, the company that is developing the carotid baroreflex activation device. Dr. Ram said that he has served on the speakers’ bureau for the Peer Group and for Advanced Health Media. Dr. Deedwania said that he had no disclosures.

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