Anti-Migraine Drugs Might Cause More Pain Than Relief For Those With Heart Disease

July 06, 1998

DALLAS, Texas, July 7 -- As if lowering risk factors for heart attack isn't headache enough, researchers report that migraine sufferers with established heart disease shouldn't take certain anti-migraine medications.

Dutch researchers report in today's Circulation: Journal of the American Heart Association that studies of blood vessels in the lab show that several migraine medications cause the vessels feeding the heart to contract. If these vessels, called coronary arteries, are already narrowed by heart disease, the contraction effects of the migraine drugs can tip the balance, resulting in chest pain and even heart attacks.

For individuals whose blood circulation is not slowed by heart disease, the scientists say that the migraine drug's contraction effects should not be dangerous.

"For most migraine sufferers this is not a problem," says Antoinette MaassenVanDenBrink, postgraduate student, pharmacology department, Erasmus University. "But if the coronary artery is already narrowed, there might not be enough reserve. In such cases, a small additional contraction may cause problems."

Therefore, doctors should be cautious about prescribing anti-migraine medications to people with established heart disease. Patients with risk factors for heart disease -- such as high blood pressure or cholesterol -- should not be prescribed this medication without a thorough evaluation showing the patient is free of heart disease, she says.

The researchers studied the coronary arteries' reaction to several anti-migraine medications after reports of chest pain and heart attack in some patients given drugs for migraine headaches. Manufacturers of some of the newer drugs have suggested their drugs are less likely to cause this type of problem, she says. However, scientists found that the drugs had similar effects on artery narrowing.

The researchers took 14 arteries from organ donors who had died from non-cardiac reasons. After measuring each artery's ability to contract and relax, they tested each drug's effect on the arteries. The drugs tested included older drugs such as ergotamine, dihydroergotamine, methysergide and its metabolite methylergometrine as well as newer drugs such as sumatriptan, naratriptan, zolmitriptan and rizatriptan.

Compared to sumatriptan, all drugs were more apt to cause the coronary arteries to contract, but are administered to patients in lower doses. The researchers determined the maximum contraction response of the arteries elicited by the drugs and the concentration of the drug required to achieve half of that maximum contraction. These values were compared to the maximum concentrations of the drugs in the blood and given a ratio.

"As far as we can predict, the compound's action is quite similar in the coronary arteries," MaassenVanDenBrink says.

But when the researchers gave in higher concentrations of the drugs and then attempted to wash them from the arteries, the artery contractions from most of the drugs decreased. However, two of the older drugs -- ergotamine and dihydroergotamine -- continued to act on the artery walls resulting in contractions. "They were much longer acting," she says. "Even after the concentrations of the drug surrounding the vessel fell, these two drugs were still acting. This is a disadvantage."

Ergotamine continued to cause artery wall contractions for up to 90 minutes, while sumatriptan and the other triptans were nearly completely gone in 30 minutes, she says.

The anti-migraine drugs, she says, are highly effective in aborting attacks of migraine headaches. However, with sumatriptan, 15 percent of patients consistently reported symptoms including pressure, tightness and pain in the chest. MaassenVanDenBrink says migraine headaches probably are caused by dilation of blood vessels in the head but located outside the brain, resulting in inflammation of tissue surrounding the vessels.

The medications "cause constriction of the vessels, relieving the headache," she says. "But constriction occurs not only in the head vessels, but also the coronary arteries."

Other researchers involved in the study included Marije Reekers, undergraduate student, Leiden University Medical Center, Rotterdam; Willem Bax, M.D., Ph.D., formerly at Erasmus University, presently at Eemland Hospital, Amersfoort; Michel D. Ferrari, M.D., Ph.D., neurologist, Leiden University Medical Center; and Pramod R. Saxena, M.D., Ph.D., chairman and professor of pharmacology, Erasmus University, Rotterdam, Netherlands.
-end-
NR 98-4917 (Circ/Vand)

Media advisory: MaasenVanDenBrink can be reached by phone at 3110 408 7537, by fax at 3110 436 6839, or by email at Maassenvandenbrink@farma.fgg.eur.nl.
(Please do not publish numbers.)
-end-


American Heart Association

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