U.S. and Canadian regulators said on Thursday they were reviewing AstraZeneca Plc's widely used stomach drugs, Nexium and Prilosec, after data raised concern about heart problems with long-term use.

But the U.S. Food and Drug Administration and Health Canada said their preliminary analyses did not show a higher heart risk and doctors should not change prescribing practices at the moment.

AstraZeneca shares closed 4 percent lower on the New York Stock Exchange. Nexium is the company's top-selling drug and was the second best selling drug in the world in 2006, according to drug information firm IMS Health. The company reported $5.2 billion in Nexium sales last year.

One Prilosec study and analyses from an ongoing Nexium study had raised concerns that long-term use might increase the risk of heart attacks, heart failure and heart-related sudden death when compared with surgery, the FDA said.

The FDA said it was still evaluating those studies plus other data and planned to finish the review in three months.

Based on everything we know now, FDA's preliminary conclusion is that the observed difference in risk of heart attacks and other heart-related problems seen in early analyses of the two small long-term studies is not a true effect, an FDA statement said.

Doctors should not change prescribing habits and patients should not alter use of the drugs, the FDA said.

Regulatory agency Health Canada said its preliminary review also had found no evidence to confirm a cardiovascular risk.

Even so, analysts said the issue could hurt sales.

This will create a shadow of a doubt about the safety of these drugs, Raymond James analyst Mike Krensavage said.

Edward Jones analyst Linda Bannister said she was not expecting sales to decline significantly at this point.

Whether or not it's a big blow for them is very dependent upon what we end up seeing as a result of this initial concern, she said, noting that Nexium accounted for about 20 percent of AstraZeneca's revenue last year.

AstraZeneca and Procter & Gamble Co., which sells over-the-counter Prilosec, said they agreed with the FDA.

It is the view of AstraZeneca that the study results conclude that the products are not associated with an increased risk of cardiac events, a company statement said.

AstraZeneca submitted information on May 29 from two studies of patients with severe gastroesophageal reflux disease who were treated with either of the drugs or surgery, the FDA said. The Prilosec study lasted 14 years, and the Nexium study followed patients for five years.

The FDA said both studies may have been skewed, in part because surgical patients tended to be younger and less likely to have risk factors for heart problems.

Fourteen other studies of patients treated for up to two years did not suggest a higher risk of heart problems with Prilosec, the FDA said.

Nexium and Prilosec are proton pump inhibitors that reduce the amount of acid produced by the stomach. Both are sold by prescription to treat acid reflux and ulcers. Prilosec also is sold over the counter for frequent heartburn. Merck & Co Inc. shares profits from the drugs.

More than 1 billion patients have taken the drugs, AstraZeneca said. Prilosec is known generically as omeprazole and Nexium is known as esomeprazole.

Other proton pump inhibitors include Prevacid, sold by a joint venture of Abbott Laboratories Inc and Takeda Pharmaceutical Co Ltd, and Wyeth's Protonix.

The FDA's primary focus is on Nexium and Prilosec, but officials are interested in data from other drugs in the class, said Dr. Paul Seligman, associate director of the safety policy and communication in the FDA drugs center.

Nexium sales already fell short of some expectations in the most recent quarter at $1.31 billion.

AstraZeneca has endured a series of late-stage product setbacks and made acquisitions to rebuild its pipeline. Last month, the company said it would eliminate 7,600 jobs as part of an expanded cost-cutting drive. (Additional reporting by Kim Dixon and Jessica Wohl in Chicago, Lewis Krauskopf in New York and Michael Kahn in London)