NEW YORK (Reuters Health) -- Three months of dual treatment with clopidogrel and aspirin after acute minor stroke or high-risk transient ischemic attack (TIA) had lasting benefit over 1 year in the CHANCE trial.
The results of 1-year follow-up are consistent with the original 3-month efficacy of the study, "suggesting clopidogrel-aspirin therapy was associated with a decrease of recurrence of stroke without an increase of hemorrhage," reported Dr. Yongjun Wang, from Beijing Tiantan Hospital, China, and colleagues online May 8 in Circulation.
The CHANCE trial was conducted at 114 centers in China. Within 24 hours of diagnosis of acute minor stroke or high-risk TIA, 5170 patients were randomly allocated to clopidogrel plus aspirin (clopidogrel 300 mg on day one, followed by 75 mg/d for 90 days, plus aspirin 75 mg/d for 21 days) or aspirin only (75 mg/d for 90 days).
The clopidogrel/aspirin combination safely decreased the 90-day risk of stroke by 32% (hazard ratio [HR] 0.68) compared with aspirin alone, but the original analysis "provided insufficient data to establish whether the benefit persisted over longer period of time beyond the trial termination," the investigators note.
At one year, 197 patients had been lost to follow-up: 111 (4.3%) in the aspirin group and 86 (3.3%) in the clopidogrel-aspirin group. The baseline characteristics of patients with and without one-year follow-up were similar.
Over the year-long follow-up, 275 patients in the clopidogrel-aspirin arm and 362 in the aspirin group suffered a stroke (10.6% versus 14.0%; HR 0.78, P=0.006). Moderate or severe hemorrhage occurred in seven patients in the clopidogrel-aspirin group and nine in the aspirin group (0.3% versus 0.4%, P=0.44).
The data suggest that "early aggressive dual antiplatelet therapy may be of benefit to patients with acute minor stroke or high-risk TIA for a long time (and) that rebound increase in risk of recurrence of stroke may not occur after the cessation of clopidogrel," Dr. Yuesong Pan from Beijing Tiantan Hospital, who worked on the study, told Reuters Health by email.
Limitations of the CHANCE trial include its restriction to Chinese patients. "The external generalizability of the findings of the CHANCE trial needs (to be) further validated in Western populations," the investigators note. On that front, the Platelet-Oriented Inhibition in the New TIA and Minor Ischemic Stroke (POINT) trial, sponsored by the National Institutes of Health, is now enrolling patients at sites largely in the U.S.
The CHANCE team also notes that the characteristics of their study patients were different from that of a typical TIA sample from population-based cohorts; women made up a minority of the cohort (33%). Also, the study enrolled only high-risk TIA patients (ABCD2 score of at least 4), which may have resulted in high event rates.
Dr. Pan noted that given the inclusion and exclusion criteria of the CHANCE study, "we still have no data to support the use of clopidogrel plus aspirin" in low-risk TIA patients with ABCD2 scores less than 4 and those presenting more than 24 hours after symptom onset.
And, Dr. Pan warned, "cautions should be taken for patients with high risk of bleeding (such as, have received anticoagulation therapy) or a contraindication to clopidogrel or aspirin."
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Disclosures
The CHANCE study had no commercial funding. One author is principal investigator in the POINT trial, with clopidogrel and placebo donated by Sanofi.