Tuesday, Sept. 3, 2013, Cleveland: Patients with clogged and hardened arteries who already have their blood pressure under control may benefit from an additional blood pressure-lowering medication, according to research from the Cleveland Clinic Coordinating Center for Clinical Research (C5Research).
The researchers found that the renin-inhibitor aliskiren tended to slow coronary disease progression and reduced the risk of death, stroke and heart attack in these patients by about 50 percent, compared to placebo, suggesting that patients with prehypertension may benefit from blood pressure lowering drugs.
The results of the AQUARIUS (Aliskerin Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) trial were presented today at the European Society of Cardiology Congress 2013 and published simultaneously in the Journal of the American Medical Association.
Aliskiren affects the body's renin-angiotensin-aldosterone system (RAAS), a hormone system that regulates blood pressure and has been shown in prior studies to play an important role in the development of atherosclerosis, or the hardening or clogging of the arteries. As a renin inhibitor, aliskiren partially blocks renin from triggering the RAAS process and is approved to treat hypertension to optimal guidelines of 140/90 mmHg, or the high end of the prehypertensive range.
AQUARIUS, a prospective, randomized, multicenter, double-blind clinical trial, was designed to test whether renin inhibition could slow or reverse the progression of coronary artery disease in patients who have their blood pressure under control in the prehypertensive range. The study also looked at whether these patients would benefit from additional blood pressure-lowering medication, even though their blood pressure was considered to be under control.
A team of researchers led by Stephen J. Nicholls, M.D., Ph.D., senior consultant to Cleveland Clinic's C5Research and Professor of Cardiology and Deputy Director at the South Australian Health & Medical Research Institute (SAHMRI) in Adelaide, Australia, used intravascular ultrasonography (IVUS) to assess the degree of coronary disease progression in 458 patients at baseline and after 104 weeks of treatment with aliskiren or placebo. IVUS is a medical imaging technology in which a small ultrasound probe is inserted via a catheter into an artery, allowing physicians to examine the inside of arteries via sonogram.
"We found that aliskiren had a moderate effect on reducing blood pressure, substantially reduced renin activity, and produced a compensatory increase in renin concentration in the blood plasma," Dr. Nicholls said. "We also saw a bit of a trend toward regression in atherosclerosis. But our primary endpoint – a decrease in the volume of disease in the artery – did not meet statistical significance."
Although not a primary endpoint, the researchers did identify a decrease in major cardiovascular events including sudden death, stroke, and heart attack in patients on aliskiren. The data indicate that patients with heart disease and blood pressure in the prehypertensive range may benefit from more aggressive treatment of their blood pressure to get it lower than current guidelines suggest.
"We have to be cautious interpreting our results on cardiovascular events because this trial was not formally designed to look at these outcomes," said Steven Nissen, M.D., Chairman of the AQUARIUS trial executive committee and Chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at Cleveland Clinic. "However, the data indicate that renin inhibition is safe in patients who have coronary artery disease and have their blood pressure under control, and it may have some beneficial cardiovascular effects."
AQUARIUS was an academically directed trial, funded by Novartis Pharmaceuticals and governed by an independent executive committee.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. More than 3,000 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. The Cleveland Clinic health system includes a main campus near downtown Cleveland, more than 75 Northern Ohio outpatient locations, including 16 full-service Family Health Centers, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and, currently under construction, Cleveland Clinic Abu Dhabi. In 2012, there were 5.1 million outpatient visits throughout the Cleveland Clinic health system and 157,000 hospital admissions. Patients came for treatment from every state and from more than 130 countries. Visit us at http://www.clevelandclinic.org. Follow us at http://www.twitter.com/ClevelandClinic.
Contact:
Wyatt DuBois, 216.904.3344, duboisw@ccf.org
Tora Vinci, 216.339.4277, vinciv@ccf.org
Journal
JAMA