Further to its preliminary review in August, when it gave the drugs a provisional go ahead, the US Food and Drug Administration (FDA) has conducted a further review of clinical studies on the safety of AstraZeneca stomach drugs Prilosec (generic name omeprazole) and Nexium (generic name esomeprazole) and found no evidence that their long term use increases the risk of heart attacks and other heart related events. The federal agency made the announcement in a statement dated yesterday, 10th December 2007.
The FDA recommends that doctors “continue to prescribe, and patients continue to use, these products as described in the labeling for the two drugs”.
Astrazeneca sent the FDA the results of two small long term studies on Prilosec and Nexium back in May. These compared the effectiveness of drugs versus surgery for severe gastroesophageal reflux disease (GERD) by randomly putting patients in either a drug group or a surgery group (one study assessed Prilosec, the other Nexium).
These two studies raised questions about whether long term use of either of the two drugs led to increased risk of heart attacks, heart failure, and heart- related sudden death, compared to patients who had surgery.
The Prilosec study showed there were more heart attacks, heart failure and heart related sudden deaths among the drug patients compared with the surgery patients. This difference occurred in the first year of the study and continued thereafter. The study lasted 14 years.
The Nexium study, which is not yet completed, and has run for 5 years so far, showed an initial higher incidence of heart related events in the drug group, but a more recent update showed there was little difference between the drug and the surgery group.
Since then, the drug company has sent the FDA more information on the Nexium study, and results from 14 other studies on Prilosec, four of which were placebo controlled trials. These new studies showed there were fewer heart related events in the drug groups compared to the placebo groups.
Following receipt of this rather large volume of data, five months later, in August, the FDA released an “early communication” on the safety of these drugs that said there was a lot of data to review, and it was proving difficult to carry out an in depth review quickly, but it was prepared to announce a preliminary okay for the two drugs and give a final decision in three months.
In yesterday’s statement the FDA said it had completed a “comprehensive, scientific review of known safety data” on the two drugs. One of the problems the agency encountered during its review of the first two studies, was that the study protocols “did not specify how heart problems, such as heart attacks, were defined or verified”, and the agency found the safety evaluation “challenging” as a result.
However, the evidence of the further studies, four of which were placebo controlled, even though they were not specifically designed to assess heart risk, and follow up is incomplete, the FDA found does “not suggest an increased risk of heart problems with the use of Prilosec or its newer formulation Nexium”.
Thus, said the FDA, based on everything it now knows about the two drugs, the reported difference in the heart related events seen in the earlier analysis of the two smaller studies “does not indicate a true effect”, and therefore the agency continues to “conclude that long-term use of these drugs is not likely to be associated with an increased risk of heart problems”.
The FDA recommends that doctors continue to prescribe, and patients continue to use the two drugs in line with their approved labelling information.
Prilosec and Nexium are proton pump inhibitors (PPIs) used to control stomach acid. They are used to treat a range of gastrointestinal conditions such as ulcers and gastroesophageal reflux disease (GERD). Some GERD conditions lead to erosion of the lining of the food pipe (esophagus) which PPIs help to heal or stop. Prilosec and Nexium are available in the US by prescription, although Prilosec is also sold as an over the counter drug for frequent heartburn.
Written by: Catharine Paddock