Study finds early drug use may thwart hypertension

Washington -- Treating prehypertensive patients with medications to postpone what is generally considered an inexorable march to full-blown hypertension is an idea glimmering on the horizon but not a concept whose time has come.

Physicians do, of course, treat prehypertension but generally by counseling patients to forget the salt shaker and get more exercise.

Now, though, findings from the recent Trial of Preventing Hypertension, or TROPHY study, hint that it just might be possible to treat prehypertension with medications to at least postpone the risk to hearts and kidneys that hypertension poses.

"There are elements of our study that suggest, yes, treatment is useful. But it is a small study and treatment lasted only two years, so we need to explore what longer treatment would do," said lead author Stevo Julius, MD, ScD, professor of internal medicine at the University of Michigan Medical School, Ann Arbor.

The study was presented March 14 at the American College of Cardiology's annual meeting and was published simultaneously in the New England Journal of Medicine.

Hypertension is a major public health problem affecting one in four Americans. The damage it inflicts on the body is well-documented, and the necessary lifestyle changes that could help prevent or at least postpone dangerous elevations in pressure often are difficult for patients to maintain.

Seeking to draw attention to a growing body of scientific literature pointing to harms that begin at much lower pressure levels than was thought, the Joint National Committee on Prevention, Detection, Elevation and Treatment of High Blood Pressure included a prehypertension category in its updated 2003 guidelines. The category covers an estimated 59 million people -- specifically, those with a systolic blood pressure of 120 to 139 mm Hg or a diastolic pressure of 80 to 89 mm Hg.

The committee recommended that physicians advise these patients to make lifestyle modifications or risk becoming one of the millions being treated with hypertension drugs.

Study findings

In the TROPHY trial, Dr. Julius and colleagues randomly assigned nearly 800 individuals whose blood pressure fell into the prehypertensive range to take either a placebo or the angiotensin II antagonist, candesartan cilexetil.

For the first two years, half the patients received the placebo and half the blood pressure medication. For the next two years, all participants received placebo to allow the researchers to detect any lasting effects from drug treatment.

All participants received guidance on diet and exercise and had regular blood pressure measurements taken.

Throughout the study, the researchers said, there was a significant difference between the two arms in the development of hypertension.

By the study's end, those who received the drug for two years had a 15.6% lower risk of developing hypertension compared with those who had received the placebo for four years.

Researchers suspected that the medication interrupted blood vessel processes that raise blood pressure -- a phenomenon studied in animals.

Studies done in rats have shown that if they are treated early enough, they will have much lower blood pressure for life, Dr. Julius said.

"Hypertension feeds on itself, causing hypertrophy of the wall of the blood vessels, and that accelerates the blood pressure process, because the vessels are narrower and the heart has to develop more pressure to overcome that resistance," he said. "So what we wanted to do was 'blood pressure healing.' "

While the results are positive, they aren't very robust, Dr. Julius said.

Another finding was the apparent safety of the medication. Serious adverse events occurred in 3.5% of the participants on the drug and 5.9% on the placebo.

Although the study was praised by many, no one, including the researchers, is ready to prescribe a medication to everyone with prehypertension. There is still a lack of evidence that aggressively treating prehypertension with drugs is going to lower cardiovascular events, noted George Bakris, MD, vice chair of the Dept. of Preventive Medicine at Rush University Medical Center in Chicago. Dr. Bakris served on the committee that revised the blood pressure guidelines.

But Dr. Bakris thinks that medications have a role to play in some prehypertensive patients, such as those with a cluster of additional risk factors. "If you take the people with metabolic syndrome -- those who are obese, with lipid disorders and a blood pressure of 130 -- I think they should be treated because of their multiple risk factors.

"Knowing what we know about continuous risk as these variables go up, I think that would be a prime subgroup to intervene with and I would argue, if you get a big enough sample, after five or six years you would see clear differences in morbidity," said Dr. Bakris. "You may not see a difference in deaths, but you would see a difference in heart attacks and strokes."

Adnan I. Qureshi, MD, professor and director of the cerebrovascular program at the University of Medicine and Dentistry of New Jersey in Newark, also would refrain from medicating patients with prehypertension. "We do not know yet that instituting pharmacological treatment at this stage is beneficial."

But the TROPHY trial is very important because it is the first to try to answer that question, Dr. Qureshi said. The TROPHY trial shows that you can prevent the progression to hypertension in prehypertensive patients and that the treatment is safe, he said. The next step will be to answer the question, "Can it actually reduce cardiovascular events?"