Researchers warned on Monday on the use of certain experimental hemoglobin-based blood substitutes, which can significantly raise the risk of heart attack and sudden death. Therefore, federal regulators should stop their use in new experiments until safety issues have been cleared up.

The warning follows a review of data from more than 3,711 patients who participated in 16 studies testing five different types of artificial blood. The review found the products nearly tripled the risk for heart attacks and boosted the chances of dying by 30 percent.

“There was an overall 30% statistically significant increase in mortality risk. There was also a statistically significant 2.7-fold increase in myocardial infarction [heart attack] associated with these products,” wrote the National Institute of Health's Charles Natanson and co-authors in the analysis, the Associated Press reports.

Therefore, the researchers from the NIH and the Washington-based consumer advocacy group Public Citizen blame the U.S. Food and Drug Administration for not requiring the companies to publish their negative findings, and for allowing additional trials to be conducted after the risk should have been apparent.

“At some point, somebody should have realized that we've tried it in trauma patients, we've tried it in surgical patients, we've tried it in stroke patients, we've tried many different formulations and we keep finding the same result. At some point, and we sort of argue in the paper that may have been the year 2000 . . . it was time to put a halt” to additional trials, Natanson said.

Before human trials, animal trials showed evidence that the product causes constriction of blood vessels that could lead to heart attack. “That sure as hell should be reported to patients or prospective patients,” Natanson said.

Even after one blood substitute trial was stopped early because safety monitors saw that patients were being injured by the product, the FDA allowed a similar trial to proceed. In that study of Northfield Laboratories' PolyHeme, 47 of 350 in the treatment group died compared to 35 of 364 in the control group. Eleven of the 350 people who got PolyHeme suffered a heart attack compared to none of the 364 who did not get the blood substitute, the researchers said.

An FDA official defended the agency, saying it had carefully weighed the risks and benefits of each study individually. The health agency also planned two meetings this week to address the very concerns raised by the review.

“FDA independently was aware of essentially the same concerns that have been raised, and indeed that is the reason we have convened this scientific workshop and is the reason why we have made careful decisions about allowing some studies to proceed and others not to proceed. Our point of view is that FDA has been highly vigilant in its oversight,” said Jay S. Epstein, director of the Office of Blood Research and Review, according to the Washington Post.

The study findings are meant to stop five human studies of blood substitutes, which are underway in eight foreign countries and at least one more human trial planned for the U.S.

Blood substitutes at issue include Baxter's HemAssist, Biopure's Hemopure, Hemosol BioPharma Inc's Hemolink, Northfield Laboratories' PolyHeme and Sangart Inc.'s Hemospan.

In an editorial accompanying the analysis in the April 28 edition of the Journal of the American Medical Association, University of Ottawa scientists said the findings should mean an end to late-stage human study of these products “until the mechanisms and potential toxicities of hemoglobin-based oxygen carriers are better understood.”