New study gets at heart of stroke risk

March 8, 2005

GAINESVILLE, Fla. --- Tossing out tobacco, noshing nutritious foods and exercising are heart healthy habits key to slashing stroke and heart attack risk. But some patients also must take medicines when these efforts aren’t enough to rein in high blood pressure, long linked to the debilitating, often deadly condition.

Now it appears a blood pressure-lowering regimen that includes drugs known as calcium antagonists is comparable to traditional therapy with beta-blockers and diuretics when it comes to warding off stroke in patients with heart disease, University of Florida researchers reported today (March 8) at the annual scientific sessions of the American College of Cardiology.

“We determined that the type of drugs involved did not affect who would go on to have a stroke,” said Rhonda Cooper-DeHoff, a research assistant professor at UF’s College of Medicine. “The bottom line is it’s not as important what you use to treat the high blood pressure as it is to get the blood pressure down.”

The study showed that smoking, diabetes, heart rhythm abnormalities, residing in the Southeast and a history of prior stroke or heart attack were among the factors linked to increased stroke risk. But lowering systolic blood pressure — the higher of the two numbers in a blood pressure reading — to less than 140 was associated with reduced risk in all of these subgroups.

In the late 1990s, a Food and Drug Administration panel concluded there was no reason to discourage use of calcium antagonists, despite early studies linking a short-acting form of the drug to an increased risk of heart attack or death in some patients. Subsequent research led by UF cardiologists and others found that aggressively lowering high blood pressure with a calcium antagonist treatment strategy not only decreases the risk of heart attack or death, it also appears to slash the chance high-risk patients will develop diabetes. But until now, little was known about how blood pressure control with these agents influences the likelihood of suffering a stroke.

More than 50 million Americans have high blood pressure, according to the American Heart Association. Elevated blood pressure is associated with up to half of all cases of coronary artery disease, a leading killer of men and women in the United States. Yet surveys have shown that 30 percent or less of patients who are known to be hypertensive comply with treatment, and even a smaller percentage achieve the targeted blood pressure goal.

Meanwhile, about 700,000 Americans a year suffer a new or recurrent stroke, according to the AHA. Nearly 163,000 die. Millions of others survive, many with permanent stroke-related disabilities. In fact, stroke is one of the leading causes of admission to long-term nursing home care and other disability-related expenses, said Dr. Thomas A. Pearson, professor and chairman of the department of community and preventive medicine at the University of Rochester Medical Center.

“Stroke turns out be very costly, both in human and quality of life terms as well as monetary terms,” Pearson said.

The new findings stem from the massive International Verapamil SR-Trandolapril study, or INVEST. The UF-led trial tracked more than 22,500 patients who were randomly assigned to one of two treatment strategies. Researchers sought to determine whether a strategy that included a sustained-release form of the calcium antagonist verapamil was at least as effective as beta-blockers and diuretics at lowering blood pressure below 140/90. The current study represents a subanalysis of data gleaned during the trial.

Calcium antagonists decrease the work the heart has to do to pump blood, reduce blood pressure throughout the body and improve blood circulation through heart muscle. Since the 1960s, beta-blockers have ranked among the most widely used drugs for the treatment of high blood pressure, but some patients can’t tolerate them because they develop fatigue or other side effects. And intensively lowering blood pressure often requires patients to take more than one medication —sometimes more than three.

In the INVEST study, sponsored by Abbott Laboratories, patients assigned to the verapamil strategy also could receive the drug trandolapril and/or a diuretic to achieve the target blood pressure or minimize side effects. If needed, those in the atenolol group also could use trandolapril, an angiotensin-converting enzyme, or ACE, inhibitor. ACE inhibitors block an enzyme in the body that causes blood vessels to narrow. If the blood vessels are relaxed, blood pressure decreases and the heart uses less oxygen to pump blood.

UF researchers, led by Dr. Carl J. Pepine, a professor and chief of cardiovascular medicine, found that 176 strokes occurred in patients taking verapamil, compared with 201 strokes among those taking the traditional drug regimen. In addition, systolic blood pressure was higher in patients who developed a stroke than in those who didn’t. Blood pressure in these patients also was less likely to be under control: 37 percent had problems reducing blood pressure to the recommended range, compared with 60 percent of those who didn’t have a stroke. Other factors also influenced who had a stroke.

“When we looked for characteristics that predicted who would go on to have a stroke, the No. 1 predictor was having had a prior stroke,” Cooper-DeHoff said. “If a patient had had one stroke, the likelihood of having another stroke that was either fatal or nonfatal was much higher.”

Health practitioners are particularly concerned because the stroke rate stopped declining around 1990, the first time it has stalled since 1900, Pearson said.

“Since blood pressure control is the very best way to prevent stroke, we need to reinvigorate our efforts to control blood pressure,” he said. “This study, I think, emphasizes there are multiple ways to do this. We need to use all tools we have, including calcium channel blockers, to control blood pressure so we can start to reinitiate those declines we previously had in the stroke rate in the past. Physicians should be reassured from this trial that long-acting verapamil gives a magnitude of protection equal to that of these other tried-and-true medications. It certainly would not be any kind of second-rate care for patients who have difficulty taking beta-blockers or thiazide diuretics.”