Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE trial)
Selected in The New England Journal of Medicine by G. Harris
Yongjun Wang, Yilong Wang, Xingquan Zhao, Liping Liu, David Wang, Chunxue Wang, Chen Wang, Hao Li, Xia Meng, D.Liying Cui, Jianping Jia, Qiang Dong, Anding Xu, Jinsheng Zeng, Yansheng Li, Zhimin Wang, Haiqin Xia, S. Claiborne Johnston
N Engl J Med 2013; 369:11-19
The use of Aspirin for secondary prevention has been shown to confer a 22% risk reduction of ischaemic stroke, according to the meta-analysis performed by the Antithrombotic Trialists Collaboration in 2009.
The benefit of adding clopidogrel to aspirin in patients presenting with unstable angina has been clearly demonstrated (CURE Trial (NEJM 2001)). The CHANCE trial evaluated a patient population who could be described to have acute cerebrovascular syndrome (Nature 2006).
The CURE trial included patients with low, intermediate and high risk of myocardial reinfarction, the CHANCE trial included only those patients, with a high risk of a cerebral reinfarction.
Most of the trials in stroke patients have not shown any benefit of the addition of clopidogrel to aspirin. In these trials clopidogrel was often started later than 24 hours after symptom onset and many of these patients had serious cases of cerebral infarction.
The SAMPRISS trial (patients with symptomatic large artery stenosis) [angioplasty & stenting plus intensive medical therapy (aspirin plus clopidogrel) vs intensive medical therapy alone] intensive medical therapy arm did better compared to previous control arms in other trials
The CHARISMA trial could show no benefit at 28 months concerning the primary endpoint (MI, stroke or death from any cause), when adding clopidogrel to aspirin vs aspirin alone.
- Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group vs. 11.7% of patients in the aspirin alone group (HR 0.68; 95% CI, 0.57- 0.81; P<0.001).
- Moderate or severe haemorrhage occurred in 0,3% of patients in both groups (seven patients in the clopidogrel-aspirin arm and eight patients in the aspirin alone arm).
- Haemorrhagic stroke occurred in 0.3% of patients in both groups.
- Death from any cause occurred in 0.4% of patients in both groups.
- Numbers needed to treat in order to prevent 1 stroke was 29.
As pointed out by the authors, the major benefit between the two groups was most evident within the 1st few days. Important points concerning the inclusion criteria to take note of include all patients were 40 years or older, patients were diagnosed with a minor stroke (NIHHS less or equal to 3), the study drug was commenced within 24 hours of symptom onset and the patients had to have a moderate to high risk of stroke recurrence (ABCD score > 3).
This trial targets a very specific window of opportunity for a specific subset of patients. It shall be interesting to see how other more potent antiplatet agents (eg. Prasugrel) and the antithrombotic agents compare. It might be prudent to exclude patients with lacunar infarcts from these trials, as it appears that they were the ones who derived most harm from long term combination clopidogrel aspirin vs aspirin alone use (SPS3 trial).