Special to Medical Device Daily
ORLANDO — Researchers reported earlier this week at the American College of Cardiology (Washington) annual meeting that a surgically implanted pulse generator system, developed by device maker CVRx (Brooklyn Park, Minnesota), appears to continue to be effective in controlling blood pressure among patients who are refractory to multiple drug regimens.
"There was concern over whether this procedure would continue to produce the blood pressure control we saw immediately after the device was implanted, and now we see that after two years, patients are still getting a benefit, possibly even a greater benefit as time goes on," said lead investigator Marcos Rothstein, MD, professor of medicine at Washington University School of Medicine (St. Louis) who presented the findings of the study.
The Rheos Hypertension System, however, involves major surgery, Rothstein said. "This is similar to operations that are performed to clear plaque from the carotid arteries in the neck, except that we do not have to open the blood vessel."
The surgery does, however, require the surgeon to open the neck and implant a cuff around the carotid arteries. The cuff is linked by wires under the skin to a pulse generator similar in size to a cardiac pacemaker that is implanted under the skin in the chest.
"What the generator does," Rothstein explained to Medical Device Daily, "is to send signals that activate baroreceptors of the carotid sinus. These signals are designed to trick the nerves into sending messages to the brain that the blood pressure is not just high but exceedingly high, forcing a cascade of molecular events that enhances the body's blood pressure lowering mechanisms.
"In practice, if a person has a blood pressure of about 180/100 mmHg," he explained, "the pulse generator makes the brain believe the blood pressure is around 220 mmHg, causing a reaction that lowers blood pressure to safer levels."
For one patient, the treatment has proved life-saving. "I went from 17 pills and an average blood pressure of 180/96 to one pill a day and my average daily blood pressure is 143/76," said David Kessel of St. Louis who underwent the surgical procedure as part of the pilot clinical trial of the device. "A flight of stairs used to get me winded and now I can walk a mile and a half on an indoor track and not even be out of breath."
The only sequelae of the procedure for Kessel were thin scars on both sides of his neck where the cuff was implanted around the carotid arteries, and another small scar on his chest where the generator is implanted.
"One of the virtues of this device is that it allows the patient to control the rhythms of blood pressure as they occur naturally. For instance, during sleep the blood pressure goes down 10 to 15 points and this device takes this into account. It is a new take on the principle of a pacemaker, but instead of being installed in the heart, it is wrapped around the carotid sinus," said Rothstein, "When a new antihypertensive agent comes on the market and drops the blood pressure three or five mmHg, it is considered a successful drug. This device, on average, drops the blood pressure 20 mmHg. This is nothing short of revolutionary in the treatment of hypertension."
Hypertension that remains uncontrolled despite optimal medical treatment is a serious health threat for patients. "We know that if you are hypertensive and your blood pressure is not controlled then you are losing 20 years of life," he said. "This device I would say is nothing less than life saving because it is able to harness the body's reactions to high blood pressure in a way that nothing else was able to before."
Rothstein, in reporting the two-year results at the ACC meeting, said the study sought to confirm initial observations that were seen with the Rheos system.
The researchers enrolled 60 patients with stage II hypertension a systolic reading that was 160 mmHg or greater and who had high blood pressure despite being on at least three different hypertensive medications including diuretics.
The Rheos device was surgically implanted and then activated one month later, and efficacy at three months, one year and two years post-activation was determined. For the first three months patients remained on their medical regimens, except in cases where hypotension occurred. The trial included 38 patients from nine centers in the U.S. and Europe. These patients completed two years of chronic device therapy; another group of 22 patients completed three years of chronic device therapy.
In the two year group, 25 of the patients were from Europe; 13 from the U.S.; 17 of the patients were women; 32 were Caucasian and 5 were African-American. The mean age of the group was 53 years. They were taking an average of 5.1 drugs to control hypertension some patients were on 7 medications. But their blood pressure was still out of control. Their mean systolic blood pressure was 183 mmHg; their mean diastolic blood pressure was 105 mmHg.
As per trial protocol, all patients were on a diuretic, 89% were taking an angiotensin modifying drug; 81% were on beta blockers; 68% were on dihydropyridine calcium channel blockers.
After two years, a reduction in systolic blood pressure greater than 20 mmHg was achieved in 53% of patients and 26% achieved a systolic blood pressure less than 140 mmHg. A significant improvement in left ventricular mass index - a decrease in the size of the left ventricle that equaled or exceeded 25 g/m2 a statistically significant change (P < 0.001) was also observed at one year. No unexpected serious adverse events occurred.
Among the 38 patients in one group, the mean decrease in systolic blood pressure after one year was 25 mmHg; after two years the decrease was 22 mmHg. Among the 22 patients being treated for three years the mean decrease was 31 mmHg. All the differences were statistically significant (p<.001) compared to baseline.
Among the 38 patient-group, the mean decrease in diastolic blood pressure after one year was 15 mmHg; after two years the decrease was also 15 mmHg. Among the 22 patients being treated for three years the mean decrease was 21 mmHg. All the differences were statistically significant (p<.001) compared to baseline.
The study is sponsored by CVRx. A Phase III trial using the Rheos system is currently enrolling up to 300 patients at 50 centers.
The company reported raising a fifth round of funding last July of $84 million to complete the Phase III trial (Medical Device Daily, July 31, 2008). Since its founding in 2001, CVRx has raised more than $209 million in private funds.