Triptan study gives researchers a headache

Migraine sufferers hail triptans, but new research raises confusing questions about its benefits and risks. Pain relief though the nose

By Owen Dyer

"This drug has changed my life," says Geraldine Charbonneau, a 31-year-old migraine sufferer from Montreal. After 15 years of being plagued by migraines, she's finally found a drug that actually controls her pain: the sumatriptan nasal spray.

"Other drugs not only didn't help," she says, "they seemed to make the pain worse. I'd completely given up seeing the doctor about my migraines. Then I read about triptans and decided to give it one more try. Now when I get a migraine, the pain usually goes away after about half an hour."

There could be trouble on the horizon for sufferers like Geraldine -- or then again, maybe not. A major new study, published in the February 24 issue of Neurology, has uncovered some puzzling findings regarding triptans, throwing into question both its positive and negative effects.

Triptans are that rarest breed of drug -- they actually work on a majority of patients with minimal side effects. They're specific to migraine headaches and work by constricting blood vessels in the brain. It's not all been sunshine, of course. Though triptans' side effects are considered minimal, and their vasoconstrictive effects are limited to the brain, patients taking triptans have occasionally complained of chest pains similar to angina. Triptans have therefore been contraindicated in patients at risk for heart disease.

STROKE RISK?
The vasoconstrictive effect in the brain has, however, led to controversy over the drug. Logically, a drug that constricts blood vessels in the brain might theoretically be expected to increase the risk of stroke. It's known that migraine sufferers are already at elevated risk of stroke. On average, they are about 40% more likely to suffer a stroke than a migraine-free person of the same age, assuming no other risk factors are present. That risk is probably doubled in those migraine sufferers who experience an aura as their headache begins. So triptans are generally not recommended for patients who have other risk factors for stroke.

Leading migraine specialist Dr Seymour Diamond, director of the Diamond Headache Clinic in Chicago and executive chairman of the US National Headache Foundation, says triptans were prescribed indiscriminately in the early days, but that has changed. "I've never seen any adverse cardiac symptoms from them. If the restrictions on the label are followed, they're wonderful drugs. It's the physicians who prescribe triptans without considering the contraindications, or patients who don't follow instructions, who get into trouble."

But there remains a broader concern that triptans might increase the risk of stroke in patients without risk factors. Nobody would expect the effect to be large, but it should be observable if a sufficiently large population were followed.

Now that study's been done. A team of British researchers followed 63,575 migraine patients, of whom 13,664 were prescribed a triptan, over seven years. They measured rates of heart disease, heart attack and stroke. Their findings are reassuring on the cardiovascular and cerebrovascular effects of triptan use, but threw up results that the researchers themselves are at a loss to explain.

MORE QUESTIONS
THAN ANSWERS
The researchers found that risk of stroke was actually lower in the triptan group than in the non-triptan group. Looking at all 63,575 migraine patients together, they found an elevated risk of ischemic stroke in all groups except women aged 45 to 59. But when they considered only those patients who had taken triptans on at least three occasions, the elevated risk seemed to disappear. The authors speculate that aborting migraines with triptans reduces the chance of a migraine-associated stroke.

But their findings contained some baffling contradictions. For one thing, the migraine sufferers who didn't take triptans had a higher risk of ischemic heart disease and stroke, yet a significantly lower risk of all-cause mortality. Sadly, the data didn't reveal what diseases were killing the triptan users at a faster rate. It seems most unlikely that triptans themselves are responsible for significantly raising mortality, since the two likeliest mechanisms by which they might harm people, stroke and heart disease, have been shown to be less common in those taking the drug. This raises a clear red flag -- there's some other difference between patients in the two arms of the study.

Previous research has also found evidence of lower all-cause mortality in middle-aged migraine patients, compared to migraine-free patients. The researchers' best guess is that migraine patients who seek treatment come from higher socioeconomic classes, and wealthier people have lower all-cause mortality. But that doesn't explain why the lower mortality was not observed among triptan users.

So this research raises as many questions as it answers. Neurologist Dr Gillian Hall, lead author of the study, admits she has no explanation for the extra deaths among patients taking triptans, though she believes that it "could be due to confounding socioeconomic factors. I think that this finding needs further study before it can be interpreted," she cautions.