Drug treatments for acid reflux are facing new FDA scrutiny

The effects of Food and Drug Administration action and a study published last month have combined to bring attention to possible adverse effects of proton pump inhibitors, the drugs commonly used to treat acid reflux.

On the regulatory side, the FDA announced Aug. 9 that a safety review had been initiated of Prilosec (omeprazole) and Nexium (esomeprazole). The agency took this step in response to data from two small, long-term studies that compared results from the use of these medications to surgery in patients with severe gastroesophageal reflux disease.

Initially, the study findings seemed to imply that chronic use of these drugs was associated with an increased risk of heart attack. A preliminary analysis, however, suggested that this outcome is not a true effect but a bias caused by the study design.

A final conclusion is expected within three months.

"The studies that suggested the signal were small and not designed to look at this endpoint. It was readily apparent, when using the standard rules of evidence, that it was easy to ascertain a number of study biases," said David A. Johnson, MD, president of the American College of Gastroenterology.

The FDA is not calling for any changes in how these drugs are used, and AstraZeneca Pharmaceuticals LP, the manufacturer of both drugs, issued a statement underscoring this agency position. Many physicians also agreed with this position.

"It would be premature to do anything clinically with respect to these data," said Nicholas J. Shaheen, MD, MPH, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine in Chapel Hill.

Transparency on safety

The agency's move is less about influencing medical practice than about being more transparent regarding its handling of potential safety issues. Physicians reported hearing very few patient concerns related to these drugs and praised the FDA for addressing this development better than similar ones in the past, such as events surrounding rofecoxib, or Vioxx.

"The FDA deserves a lot of credit for mitigating the concerns of patients," said A. Mark Fendrick, MD, professor of internal medicine at the University of Michigan, Ann Arbor. "We had a few patients call asking our advice and what to do, but far fewer than when safety concerns were raised about Vioxx."

Meanwhile, issues have emerged about H2 blockers, which also are used to treat GERD. A paper in the August Journal of the American Geriatrics Society linked continuous use of these drugs by elderly African-Americans to a more than doubling of the risk of developing cognitive impairment. The authors are urging that consideration be given to the impact on cognitive functioning, as well as the vital organs, before prescribing this medicine to older patients.

"We need to distinguish the benefits and harms for any medication taken for a chronic condition on the heart and the kidney and, now, on the brain," said Malaz Boustani, MD, MPH, lead author and assistant professor of medicine at Indiana University School of Medicine and a research scientist at the Regenstrief Institute in Indianapolis.

A small number of papers have associated these drugs with cognitive problems. The potential of this drug to cause confusion is also a well-known but rare side effect. Experts said, however, that this study, which was observational, was not enough to change medical practice, although this possibility may be worth pursuing in future research.

"Until more definitive data are available, it's difficult to know how to handle this clinically," Dr. Shaheen said.