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Low-dose Periostat (Doxycycline) Shows Benefits in Patients with Heart Failure: Presented at AHA

By Jill Stein

CHICAGO, IL -- November 20, 2002 -- Preliminary data suggest that the commonly used antibiotic doxycycline (Periostat), which is widely used to treat gum disease, reduces C-reactive protein (CRP) levels by nearly 50 percent in patients recently hospitalized for an acute coronary syndrome.

The results, presented here November 18 at the 2002 Scientific Sessions of the American Heart Association (AHA), are drawn from the Metalloproteinase Inhibition with Low-Dose Doxycycline to Prevent Acute Coronary Syndromes (MIDAS) pilot trial.

Dr. David Brown, director of interventional cardiology and cardiac catheterization laboratories at Beth Israel Medical Center in New York, United States, and principal investigator of the trial, reported the results.

For the investigation, 50 patients with recent acute coronary syndromes were randomized to low-dose doxycycline (20 mg BID) or placebo. The 20 mg tablet, taken twice daily, provides a sub-antimicrobial dose of the antibiotic.

At enrollment, the two treatment arms had similar demographic and clinical characteristics, including age, sex, and frequency of hypertension, diabetes, smoking, prior cardiac history, extent of coronary disease, presentation with acute myocardial infarction or unstable angina, and need for a percutaneous coronary intervention.

At six-month follow-up, sub-antimicrobial dose doxycyline significantly reduced CRP levels by 45.8 percent compared to baseline values (p<0.05). The drug was also associated with a 33.5 percent reduction in interleukin-6 and a 50 percent reduction in metalloproteinase (MMP)-9 activity (p<0.05).

There was no difference between the low-dose doxycycline and placebo groups in the composite end point of cardiovascular death, myocardial infarction, or troponin-positive unstable angina. Dr. Brown emphasized, however, that the study was too short to permit assessment of a significant difference between the two groups with respect to this end point.

Low-dose doxycycline was safe with no discontinuations due to treatment-related side effects. Two patients in the placebo group discontinued treatment prematurely. Both developed drug rashes that were probably due to another drug they had started at the same time, Dr. Brown said.

"The findings are exciting, since research is now showing that CRP is both a key marker of inflammation leading to future acute coronary events, but also that CRP itself may contribute to the initiation and progression of atherosclerosis," he noted.

Finally, he said he hopes to conduct a larger study to explore the effects of low-dose doxycycline on vascular inflammation.

Low-dose doxycycline is marketed under the brand name Periostat by CollaGenex Pharmaceuticals.

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