News Release

Gout drug could offer hope for heart failure patients

Peer-Reviewed Publication

Johns Hopkins Medicine

A medication commonly used for gout holds possibilities for the treatment of heart failure, Johns Hopkins researchers report. It's a drug that works by a new principle, namely, directly decreasing heart muscle's need for energy and making it contract more efficiently.

When allopurinol was injected into the hearts of nine patients with congestive heart failure, it significantly improved the organs' efficiency. Results are reported in the Nov. 13 issue of Circulation, an American Heart Association journal.

Heart failure can be compared to a car that's out of tune. The heart still functions, but it's not efficient. As the heart worsens, it must work harder, requiring stepped-up, energy-producing reactions that enable it to contract and pump blood. In the Hopkins study, allopurinol improved overall heart efficiency. The hearts of patients treated with the medication had a 20 percent reduction in energy consumption with no reduction in contraction strength.

"Allopurinol represents a novel potential strategy for the treatment of heart failure," says Joshua M. Hare, M.D., senior author of the study and director of Hopkins' heart failure research program. "It allowed the heart to use less oxygen without any detrimental effects on its function."

For the study, Hare and colleagues looked at nine patients (seven men and two women) with dilated cardiomyopathy – a cause of severe heart failure in which the lower left chamber of the heart becomes enlarged and weakened. Patients were taking standard medications for congestive heart failure, including ACE inhibitors and beta blockers.

Allopurinol was infused directly into the heart while researchers recorded the patients' heart performance. The research team also took tissue samples from cardiomyopathy patients undergoing heart transplant and used them to measure amounts of xanthine oxidase (XO) – an enzyme involved in normal tissue metabolism.

XO contributes to the heart's demise in ways not yet understood. The researchers found that amounts of XO were significantly higher in heart failure patients.

Researchers believe that when XO goes awry, it releases free radicals that disrupt the body's energy-producing machinery. Allopurinol works by inhibiting this. In gout, the drug blocks uric acid crystals from building up in the joints and causing inflammation, swelling and pain.

Hare plans to start clinical trials of allopurinol for heart failure within the next year. The study was supported in part by the National Institutes of Health. Other authors were Thomas P. Cappola, M.D.; David A. Kass, M.D.; Gregory S. Nelson, Ph.D.; Ronald D. Berger, M.D., Ph.D.; Gisele O. Rosas, Ph.D.; Zoulficar A. Kobeissi, M.D.; and Eduardo Marbán, M.D.

Marbán holds equity in Paralex Inc., a company that seeks to investigate the therapeutic potential of xanthine oxidase inhibitors for various indications. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. The present study was completed before Paralex was incorporated, and no financial support was received from Paralex.

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Cappola, T.P., et. al., "Allopurinol Improves Myocardial Efficiency in Patients with Idiopathic Dilated Cardiomyopathy," Circulation, Nov. 13, 2001, Vol. 104.

Related Web sites:

Johns Hopkins Cardiomyopathy and Heart Transplant Service
http://www.med.jhu.edu/heart.

American Heart Association
http://www.americanheart.org

Media contact: Karen Blum 410-955-1534, Email: kblum@jhmi.edu

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