Bigger Doses of Heart Drug Perilous, 2 Studies Report : Medicine: Just slight increases of heparin double risk of severe strokes, researchers say. But the FDA contends it is generally safe.

WASHINGTON — Slightly increasing the dose of a drug commonly used to treat heart attacks almost doubles patients’ risk of devastating strokes, two studies published Monday said.

The findings on the drug heparin caused researchers to suspend the studies in April, and in Monday’s edition of the journal Circulation they warned doctors to be careful.

“We didn’t know there was a dark side to heparin,” study co-author Dr. Eric Topol of the Cleveland Clinic said. “We learned it has a very narrow window for safety.”

But the Food and Drug Administration insists most patients get lower doses that are safe.

“The message should be don’t panic,” Dr. Janet Woodcock of the FDA said. “We’re unconvinced there’s widespread use of higher doses of heparin.”

Despite 80 years of use, nobody knew the upper limits of heparin, which is commonly given--along with clot-dissolving drugs--to thin the blood of heart attack victims. All such drugs pose the danger of uncontrolled bleeding and stroke.

Topol and another group of investigators at Harvard accidentally discovered heparin’s upper limit while comparing its effectiveness to that of an experimental drug called hirudin.

Just months into the study, researchers noticed that both drugs increased the risk of stroke two times above that normally seen in heart attack patients.

Twenty-six of Topol’s 2,564 heart attack victims who received either heparin or hirudin suffered a stroke. Thirteen of the 713 Harvard patients suffered a stroke. More than half of the stroke victims died.

The risks from each drug were comparable.

That this occurred with hirudin wasn’t so surprising. Hirudin, derived from leeches, is a very potent anticoagulant that is still in the testing phase, when risks are discovered. But Topol says he was shocked that heparin given at just 20% above normal doses was dangerous.

The recommended heparin dose is 5,000 units initially, with hourly injections individualized so the patient’s blood takes twice as long as normal to clot. Topol increased that to three times the normal clotting time.

The trials were suspended April 8. But Topol and the FDA decided against immediately alerting outside doctors.

The FDA insists most doctors already use very low doses of heparin. “If we’d felt people were being put at risk, we would have” warned doctors, Woodcock said.

Topol disagreed. “I know many cardiologists who are much more aggressive with heparin than what we have advocated.”

The two U.S. trials were restarted in May with routine heparin doses and hirudin doses cut in half. The 3,000 patients enrolled since then have reported no problems.