Ticagrelor or clopidogrel?
Ticagrelor now becomes the second antiplatelet agent to have shown benefits on top of aspirin in the minor stroke and high-risk TIA population. Clopidogrel also showed a reduction in major ischemic events in the POINT trial as well as in the Chinese CHANCE trial in similar populations.
Dr. Amarenco pointed out, however, that until now the only treatment that has been shown to reduce disabling stroke in the minor stroke/high risk TIA population in a single trial is aspirin. “The CHANCE and POINT trials of clopidogrel did not show a reduction in disabling stroke individually but this was observed when the trials were combined,” he noted.
“Clinicians will now have to choose between ticagrelor and clopidogrel. We don’t have a head-to-head comparison yet but ticagrelor is effective in all patients whereas clopidogrel may not be as effective in the large subgroup of patients who carry the loss of function gene which make up about 20% of the western population and about 40% of the Asian population,” he said.
“It is very important in the acute phase of stroke to know that the antiplatelet drug is immediately effective as the risk of a recurrent event is highest in the first few hours and days.”
Dr. Amarenco acknowledged that some hospitals may favor clopidogrel because of cost, as it is available generically so is much cheaper than ticagrelor. “But we are only talking about 30 days of treatment, so cost is not too much of an issue,” he pointed out.
The Food and Drug Administration recently approved use of ticagrelor in this indication on the basis of the THALES study.
“It is great news that vascular neurologists now have a new player for reducing future stroke in these patients,” Dr. Amarenco said. Clopidogrel is not approved for this indication but is recommended in American Heart Association/American Stroke Association guidelines, he added.
Dr. Johnston, who was also the lead investigator of the POINT trial with clopidogrel, suggested that it is more important to get patients on dual-antiplatelet therapy rather than worrying too much about which agent to use. “I think we can use aspirin plus either ticagrelor or clopidogrel. The effect on disabling stroke was not significant in POINT but it did reach significance in a meta-analysis combining POINT and CHANCE,” he noted.
He said that choosing between ticagrelor and clopidogrel is tricky without head-to-head data. “Differences in the studied populations makes direct comparison of the trials unwise,” he stressed.
Dr. Johnston pointed out that neither of the clopidogrel trials included moderate strokes (NIHSS scores of 4 and 5) in their study population. “We only have data on ticagrelor for this important group, which accounted for 30% of the THALES study population,” he noted.
“Some people are concerned about the limited efficacy of clopidogrel in large subgroups of patients who do not metabolize it to its active form, but on the flip side, clopidogrel is cheaper – though a 21- to 30-day course [of ticagrelor] probably isn’t that costly – and has more data in combination with aspirin,” he added.
Dr. Johnston said that the approval of ticagrelor for this new indication was “reassuring,” and “provides some air cover for practitioners given the risks of hemorrhage.” He added: “We didn’t bother with an FDA submission after POINT because it was an NIH-sponsored trial. The drug company normally prioritizes regulatory approvals for marketing purposes but their interests were limited because clopidogrel has exceeded its patent life.”
Cost-utility analyses are not yet available, but Dr. Johnston noted: “I suspect both drugs will have substantial benefits and be cost saving. Stroke is expensive, particularly disabling stroke.”
Dr. Johnston said that the more important message is: “Get these people on dual-antiplatelet therapy as soon as possible. Too many patients are not getting the right treatment immediately after symptom onset. We have lots of work to do here.”