FDA Issues Safety Findings for Omeprazole, Esomeprazole

The FDA has announced the results of a safety review of the drugs omeprazole, marketed as Prilosec, and esomeprazole, marketed as Nexium, saying that long-term use of these drugs is not likely to be associated with an increased risk of heart problems. Thus, the agency recommends that health care professionals continue to prescribe and patients continue to use these products as described in their package labeling.

On May 29, 2007, AstraZeneca, which manufactures both drugs, sent the FDA a preliminary review of data from two small long-term studies involving patients with severe gastroesophageal reflux disease, or GERD, who were being treated with either omeprazole or esomeprazole. Those early findings raised concerns that long-term use of these drugs could increase patients' risks for myocardial infarction, heart failure or sudden death from cardiac causes. The FDA requested and received additional data on two drugs, including information on patient follow-up from the two long-term studies, as well as pooled analyses of other controlled clinical studies.

The FDA's preliminary review of those data indicated that they did not, in fact, suggest an increased risk of heart problems for patients treated with omeprazole or esomeprazole, and the agency said it saw no need for health professionals to change their prescribing practices or use of the two drugs. FDA officials noted that they expected to wrap up their evaluation within three months and would release their final conclusions at that time.

The FDA safety review was based primarily on two studies. The first was a 14-year European-based study involving patients with severe GERD. About half of the patients were randomly assigned to a group that would receive the drug omeprazole (n = 154), and half were assigned to a group that would have anti-reflux surgery (n = 144). The FDA's analysis found that eight patients who received omeprazole died of heart-related causes (i.e., heart failure, sudden death) and nine had nonfatal heart attacks. Among patients assigned to the anti-reflux surgery group, two died of heart-related causes, and two had nonfatal heart attacks.

On reviewing the study data, however, the agency discovered that there were significant differences in the health of the patients assigned to each of the two groups. At baseline, six of the patients who received omeprazole had a history of heart attack; three of these patients died of heart-related causes. None of the patients assigned to the surgery group had a history of heart attack. In addition, the median age of patients assigned to the omeprazole group was four years older than the median age of those assigned to the surgery group. By the end of the study, a greater percentage of patients who received omeprazole (88 percent) were 60 years of age or older than those who had surgery (77 percent), suggesting that, overall, patients in the surgery group tended to be younger and healthier.

In the second study, which is still ongoing, patients with severe GERD were randomly assigned to receive esomeprazole (n = 266) or laparoscopic surgery (n = 288). In this study, the number of patients who experienced heart problems was similar in both treatment groups: Five patients treated with esomeprazole and four patients who underwent laparoscopic surgery suffered nonfatal heart attacks.

Based on these studies and supporting evidence from 14 comparative studies of omeprazole, the FDA has concluded that the reported difference in the frequency of heart attacks and other heart-related problems seen in earlier analyses does not indicate the presence of a true effect.