MONDAY, April 15, 2002 (HealthDayNews) -- In its first test in people, an experimental drug significantly boosted blood levels of an important fat known to prevent heart attacks.
Dutch researchers found the drug raised levels of high-density lipoprotein-C (HDL-C), the so-called "good" cholesterol, by 34 percent after only four weeks and without major side effects. HDL is inversely related to heart and vessel disease: As blood levels of the fat increase, a person's risk of heart attack falls.
However, the new study, appearing in an upcoming issue of Circulation, didn't follow patients long enough to see if they received any protection from the drug, whose drawing board name is JTT-705. Japan Tobacco Inc. funded the work, and is developing the drug. Although other researchers have shown that boosting HDL appears to reduce the risk of cardiovascular ailments, the results haven't been conclusive.
"Lots of people would like to think [raising HDL] is going to be important, but we just don't know" at this point, says Dr. Sander Robins, a cholesterol expert at Boston University School of Medicine. Robins helped conduct an earlier trial with a different HDL-raising drug, and found it modestly elevated the blood fat. People with higher HDL in that study also had a lower risk of heart and vessel problems, but the drug could explain only some of that effect.
"You could not account for the bulk of the reduction in [cardiovascular] events by the magnitude of the HDL change," Robins says. "Every drug has multiple effects, and something else is going on that's not easily measurable."
On the other hand, Robins says, the logic behind trying to improve heart health through HDL has strong support from years of epidemiological studies.
"HDL cholesterol is clearly a major [cardiovascular disease] risk factor. It's just as potent a risk factor as high LDL cholesterol," he says. LDL is the "bad" form of cholesterol. Each 1 percent increase in HDL-C lowers the risk of cardiovascular illness and death by between 2 percent and 3 percent.
HDL's job is to ferry fats away from the vessels and into the liver. One obstacle to this function is a molecule called cholesteryl ester transfer protein (CETP), which breaks down HDL. Earlier work in rabbits showed that blocking the action of a blood molecule with JTT-705, a CETP inhibitor, sharply raised HDL and reduced atherosclerosis.
In the new study, a team led by Dr. John Kastelein, a vascular medicine specialist at the University of Amsterdam, looked at varying doses of JTT-705 and dummy treatment in 198 men and women with mildly elevated total cholesterol.
Four weeks on the highest dose of the drug, 900 milligrams a day, led to a 37 percent drop in CETP activity and a 34 percent increase in HDL. It also decreased LDL by 7 percent, on average, the researchers say.
The drug seemed relatively safe, with no serious side effects. It did lead to diarrhea and flatulence in some patients, but no subjects dropped out of the study.
Nearly 50 million Americans have a combination of low HDL and high triglycerides, another class of blood fat that, when elevated, can do cardiovascular damage. These patients are "a major problem for practicing physicians," says Dr. Bryan Brewer, chief of the molecular disease branch of the National Heart, Lung, and Blood Institute. The problem is a lack of therapies that can boost the first while lowering the second.
"If [JTT-705] turns out to be very effective in raising HDL and changing cardiovascular disease endpoints, I think it will be a great addition to our armamentarium of drugs," Brewer says.
What To Do
For more on cholesterol, try the University of Michigan or the Texas Heart Institute.
Want to estimate your risk of having a heart attack? The National Institutes of Health has an online calculator.
