Craig LeMoult
PR Writing

Radio Stories


Drugs in Trials for Asthma, Alzheimer’s and Chronic Lung Disease
May Cause Heart Disease

Columbia University Medical Center Research Shows Inhibitors of PDE4 Enzyme Can
Have Serious Cardiovascular Side Effects

Drug Companies Warned to Screen For Heart Disease When Testing These Drugs


NEW YORK, NY October 7, 2005 - New research from Columbia University Medical Center is calling into question the safety of a class of drugs currently in phase III trials for chronic lung disease and asthma, and also being considered as a therapy for Alzheimer’s disease. The research, published in the October 7 issue of Cell, shows that inhibiting an enzyme called phosphodiesterase type 4 (PDE4), can cause heart failure and arrhythmias in mice, and may put patients, particularly the elderly, in danger of serious heart disease.

Drugs that inhibit this enzyme were hoped to be more effective in treating chronic obstructive pulmonary disease (COPD) than current options. COPD is the nation’s fourth leading cause of death. The drugs have also shown promising results in preliminary asthma trials and are now undergoing phase III testing. Other activities of PDE4 inhibitors may slow the progression of Alzheimer’s disease.

But the study, led by Andrew R. Marks, M.D., director of the Center for Molecular Cardiology and chair of physiology and cellular biophysics at Columbia University Medical Center, found that as mice age, those with no PDE4D activity developed abnormally large hearts that pumped inefficiently, a hallmark of heart failure in people. The study showed that PDE4 inhibitors cause a leak in an ion channel inside the heart muscle. Earlier research by Dr. Marks has shown that this leak can spark sudden heart-stopping arrhythmias, in addition to causing heart failure over time.

“The danger of potentially serious and irreversible cardiac damage needs to be weighed against the possible benefits of PDE4 inhibitors in treating diseases such as Alzheimer’s, asthma and chronic lung disease,” said Dr. Marks. “As the fallout from the Vioxx case has shown, when testing new drugs it’s important to ask the right questions ahead of time so you know what kinds of potential problems to look for. In this case, the studies suggest that investigators should put a high priority on screening for heart disease in patients receiving PDE4 inhibitors.”

Historically, young people who have been treated with PDE inhibitors have had a higher risk of heart arrhythmia, but not heart failure, because their age. But PDE4 inhibitors are now being tested for use to treat Alzheimer’s disease and chronic lung disease, and the Columbia study suggests that there could be an increased risk of arrhythmias and heart failure in older patients.


Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, medical education, and health care. The medical center trains future leaders in health care and includes the dedicated work of many physicians, scientists, nurses, dentists, and other health professionals at the College of Physicians & Surgeons, the School of Dental & Oral Surgery, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. With a strong history of some of the most important advances and discoveries in health care, its researchers are leading the development of novel therapies and advances to address a wide range of health conditions.