N Engl J Med 2013 Jun 26
Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.
Abstract
Background
Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.
Methods
In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.
Results
Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.
Conclusions
Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).
Related Questions
Do you generally switch aspirin to another antiplatelet agent if a patient has a non-embolic ischemic stroke and isn't a candidate for DAPT?
I do tend to switch, mainly to impress the patient that I am trying hard to prevent another stroke, and not because there is clear evidence of one antiplatelet over another. Clopidogrel or ticagrelor would be candidates, or I might add cilostazol to aspirin, as this combination has little bleeding r...
When do you consider starting short-term DAPT in patients who present more than 24 hours after the onset of a high-risk TIA or minor stroke syndrome?
The literature states that DAPT is most effective when started within the first 24 hours after such an event, but is still effective as far as 72 hours later. So if the patient presents more than 24 hours later, but not later than 72 hours, I would still start it then but would want a CT scan first.
Would you consider dual antiplatelet therapy for stroke prevention for ICAD in patients with a history of SAH?
It depends on the strength of the indication for DAPT and the cause of SAH. It is important to keep things in perspective: the absolute risk reduction from DAPT for secondary stroke prevention in the POINT, CHANCE, and THALES trials was small (on the order of 1-3% absolute risk reduction) for minor ...
Does the overall conclusion of the CHANCE-2 trial make ticagrelor + ASA a worthwhile transition given the data showing cumulative hazard of stroke diverged during the first week and was subsequently similar, which suggests the benefit of ticagrelor over clopidogrel is seen predominantly soon after stroke?
Given the fact that clopidogrel costs 11 cents a day and ticagrelor costs almost $8/day and the fact that most patients will not be tested for slow CYP2c19 metabolizer (or have the results back in a timely fashion), it seems that the combination of ASA plus clopidogrel is the best option from a publ...
Would you generalize the data from the CHANCE-2 trial to a broader clinic population given that the study was specific to Han Chinese patients?
I believe the results of CHANCE-2 (Wang et al., PMID 34708996) are generalizable to non-Chinese populations. CHANCE (Wang et al., PMID 23803136), performed in China, and POINT (Johnston et al., PMID 29766750), performed worldwide but excluding China, produced strikingly similar results in dual antip...
Would you recommend short-term dual antiplatelet therapy for a patient who received tPA, and is otherwise eligible for dual antiplatelet therapy per POINT or SAMMPRIS trial?
I would agree. tPA is not a contraindication to the later prescription of dual antiplatelet therapy. I do not see a definite answer to the question of 21 days versus 90 days, the CHANCE trial (Wang et al., PMID 23803136) supports 21 days and the POINT trial (Johnston et al., PMID 29766750) 90 days. ...
What duration of dual antiplatelet therapy do you use for secondary prevention of ischemic stroke due to intracranial atherosclerotic disease?
It is a fair question that we don't have a solid evidence-based answer for. I agree that the SAMMPRIS trial was driven by events within the first 30 days, although this was primarily driven by procedure-related events in the stented group. We do know that intracranial athero (ICAS) risk of stroke re...