Aug. 9 (Bloomberg) -- U.S. regulators disclosed a safety review of AstraZeneca Plc's top-selling acid-reflex drugs Nexium and Prilosec after two small studies linked the medicines to heart attacks and death. AstraZeneca shares fell the most in three months.

At the same time, the Food and Drug Administration said in a statement today that its ``preliminary conclusion'' is the two drugs don't pose increased risks. The agency urged patients to continue using AstraZeneca's prescription Nexium and Prilosec and over-the-counter Prilosec, sold by Procter & Gamble Co. of Cincinnati.

More than 1 billion patients worldwide have taken the drugs to reduce the amount of acid produced by the stomach and to treat ulcers and persistent heartburn, London-based AstraZeneca said. The products brought in a combined $1.63 billion in the second quarter, about 22 percent of the company's sales. Analysts said any safety concerns may affect sales.

``It will, in the end, create a lot of uncertainty among prescribers,'' said Lars Hevreng an analyst at SEB Enskilda in Stockholm, in a phone interview today. ``The headlines are out, and people of course will ask their doctors in the next few weeks and months what's it all about.''

Shares of AstraZeneca fell 87 pence, or 3.5 percent, to 2,430 pence at the close of trading in London, after earlier losing as much as 13 percent. They've declined 11 percent this year, making the company the third-worst performer on the Bloomberg Europe Pharmaceutical Index of 13 companies. P&G shares fell 19 cents to $64.97 at 4:01 p.m. in New York Stock Exchange composite trading.

Avandia, Vioxx

The FDA this year has also reviewed reports of heart dangers found in studies of GlaxoSmithKline Plc's diabetes pill Avandia. The agency has faced criticism from Congress over its ability to monitor drug safety since Merck & Co. was forced to withdraw its Vioxx painkiller in 2004 because the drug was linked to elevated risks of heart attacks and strokes.

``The only thing I see out of all this between Astra and Glaxo and Avandia is the FDA is getting massively risk averse,'' said Navid Malik, an analyst at Collins Stewart in London, in a phone interview.

Drug agencies in the U.K. and Australia have also reached preliminary conclusions supporting the safety of Nexium and Prilosec after AstraZeneca submitted two long-term studies to regulators worldwide on May 29, the FDA said. Health Canada said in a separate statement that its preliminary review of the data didn't ``confirm'' heart risks.

Three Months

``We're continuing to review the information over the next three months and at the end of that, we'll release a complete analysis,'' FDA spokeswoman Rita Chappelle said today in a phone interview. ``Health-care providers and patients should not change their prescribing practices or use of the drugs.''

The information released by the FDA doesn't give doctors and patients information they can act on, said Brian Strom, a professor of biostatistics at the University of Pennsylvania School of Medicine in Philadelphia, in a telephone interview. Still, the FDA had little choice, he said.

``They have been in the past severely criticized for not relaying information when they have it, and this is a logical response from an agency under pressure,'' Strom said in a telephone interview today. ``If this is what the public wants, that's fine. But then the public has to not overreact.''

Nexium is the world's fourth best-selling drug, with $5.2 billion in revenue last year, ranking behind Pfizer Inc.'s cholesterol pill Lipitor, Glaxo's asthma inhaler Advair and Plavix, a blood thinner made by Sanofi-Aventis SA and Bristol- Myers Squibb Co.

Class of Drugs

Nexium and Prilosec belong to a class of drugs known as proton pump inhibitors, used to prevent damage caused when excess stomach acid rises into the esophagus. The drugs treat heartburn and prevent ulcers by blocking the release of acid.

AstraZeneca introduced Nexium in the U.S. in 2001 to replace the older Prilosec, which was losing patent protection. The company sold rights for over-the-counter Prilosec tablets to P&G to support the product, once the world's best-selling medicine. Lower-cost generic copies of Prilosec, called omeprazole, are available with a prescription.

Similar drugs include Aciphex, from Eisai Co., Prevacid, produced by a joint venture of Abbott Laboratories and Takeda Pharmaceutical Co. and Protonix, from Wyeth.

AstraZeneca submitted a 14-year study comparing use of Prilosec to surgery in treating acid-reflux disease, as well as an initial analysis of a continuing five-year study on Nexium. The observed increase in heart attacks and other cardiovascular complications may have stemmed from health differences between patients getting the drugs and comparison groups, the FDA said.

``It's nothing that patients should worry about,'' AstraZeneca spokesman Steve Brown said today in a telephone interview. ``Patients shouldn't come off Nexium, or Prilosec, because of these studies.''

To contact the reporters on this story: Catherine Larkin in Washington at clarkin4@bloomberg.net; Andrea Gerlin in London agerlin@bloomberg.net

Last Updated: August 9, 2007 16:07 EDT