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9/11/2001

Drug Decreases Arterial Stiffness

Kate Traynor

An experimental drug—the first in a new pharmaceutical class—seems to reverse blood-vessel stiffening in people over 50 years old who have elevated systolic blood pressure and reduced vessel elasticity.

The drug, a thiazolium derivative known as ALT-711, breaks crosslinks that have formed between the sugar and protein moieties in arteries and other tissues. These crosslinks can stiffen arteries and the heart.

Arterial compliance in the 62 patients who took the drug improved nearly 15 percent after 28 days of treatment and remained significantly improved at 56 days, the end of the study. There was no change in arterial compliance among the 31 similar patients who received placebo instead of ALT-711.

The results of the study appeared in an early-release online report also scheduled for publication in the Sept. 25 issue of the American Heart Association journal Circulation.

Patients' aortic pulse-wave velocity, another measure of blood-vessel stiffness, fell 7 percent in the ALT-711 group by the end of the study but not midway and did not change in the placebo group.

At the end of the 56-day study, arterial pulse pressure—the difference between the systolic and diastolic pressures—had fallen an average of 5.3 mm Hg in ALT-711 users and 0.6 mm Hg in the placebo group. The report’s authors noted that increased pulse pressure and reduced vessel compliance are "dominant risk factors for cardiovascular disease."

Nine U.S. clinical centers enrolled 93 patients in the study, randomly assigning twice as many people to take a single dose of three 70-mg ALT-711 tablets once daily for 56 days as to take identical-appearing placebo tablets. Patients who enrolled in the study were, on average, in their mid-60s. About a quarter of the patients had stable type II diabetes mellitus.

The participants were allowed to continue taking their antihypertensive medications during the study. About 90 percent of the enrollees took at least one antihypertensive drug. Angiotensin II-receptor blockers and angiotensin-converting-enzyme inhibitors were the most commonly used antihypertensives.

Fifty-five percent of the patients in the ALT-711 group and 61 percent of those taking a placebo had at least one adverse event during the study. The report listed atrial fibrillation and noncardiac chest pain as serious adverse events but did not note whether patients with these symptoms were taking ALT-711 or the placebo. Another serious adverse event, dizziness, was reported by 16 percent of placebo users and 13 percent of patients in the ALT-711 group.

Alteon Inc., the manufacturer of ALT-711, announced recently that it started a Phase IIb study of dosages in addition to 210 mg daily; patients will take the drug for six months instead of 56 days.

Funding for the study published in Circulation was provided by Alteon and the National Institute on Aging.