Drug Slows Onset of Hypertension
Wednesday, March 15, 2006
Temporarily giving anti-hypertensive medicines to people whose blood pressure is just below the threshold for high blood pressure delays the onset of that disease for only a short time, a new study has found.
Researchers had hoped that, by briefly intervening in the "prehypertensive" stage, they might abort the disease and give patients a long period of normal blood pressure. But that turned out not to be the case.
What the researchers found was that if someone with borderline high blood pressure took medicine for two years and then stopped, that intervention slowed the rise of his blood pressure into the hypertensive range by one year.
"There is a significant effect. It is not an overwhelming effect. It is a modest effect, but it has been proven," said Stevo Julius, a physician at the University of Michigan Medical School, who led the study.
Most people with prehypertension develop hypertension, a chronic disease that raises a person's lifetime risk for heart attack, stroke and kidney failure. People can lower their blood pressure with exercise, diet and weight loss, but the effect is small and lifestyle changes are difficult for many to achieve or sustain.
This study of drug treatment of prehypertension was an effort to find a more effective intervention, Julius said. The results were presented yesterday at the American College of Cardiology meeting in Atlanta, and will be published in the New England Journal of Medicine.
Prehypertension is a term coined in the 2003 federally sponsored guidelines for high blood pressure treatment. It was previously called "borderline hypertension" or "high-normal blood pressure." In some people, it is a stable condition. In others, it is the early stage of a complicated process in which the walls of arteries thicken and become less able to relax -- a vicious cycle that slowly drives blood pressure up.
When young rats bred to develop high blood pressure are given a drug called an ACE inhibitor for a short period, the onset of hypertension in the animals is greatly delayed. ACE inhibitors limit production of two hormones that raise blood pressure and are involved in the body's regulation of salt. Another class of drugs, angiotensin-receptor blockers (ARBs), have a similar action but at a different stage in the activation of those hormones.
Julius and his colleagues persuaded the pharmaceutical company AstraZeneca to pay for a study to see if the effect seen in rats might occur in people, as well. AstraZeneca makes an ARB named candesartan, sold under the brand-name Atacand. All ARBs are still under patent and are much more expensive than generic ACE inhibitors.
About 70 million Americans have prehypertension -- blood pressure in the 120-139/80-89 range, measured in millimeters of mercury -- so a study showing benefit of candesartan treatment could be highly profitable to the company.
The researchers randomly assigned about 800 people with prehypertension to take candesartan or a placebo for two years. After that, everyone took a placebo for two years.
At the end of four years, 240 people who took a placebo the whole time had developed hypertension -- nearly two-thirds of that group. In the candesartan group, 208 people had become hypertensive.
The average time to development of hypertension in the placebo group was 2.2 years, while it was 3.3 years in the candesartan group. The drug slowed the onset of the disease but not by much.
Most people taking candesartan would not benefit from it but would go on to develop hypertension, anyway. In fact, out of 10 people taking the drug for two years, only one would avoid becoming hypertensive at the end of four years.