Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack

Abstract

IMPORTANCE Dual antiplatelet therapy with clopidogrel and aspirin is effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA). Uncertainties remained about the optimal duration of dual antiplatelet therapy for minor stroke or TIA.OBJECTIVE To obtain precise estimates of efficacy and risk of dual antiplatelet therapy after minor ischemic stroke or TIA. DESIGN, SETTING, AND PARTICIPANTSThis analysis pooled individual patient-level data from 2 large-scale randomized clinical trials that evaluated clopidogrel-aspirin as a treatment to prevent stroke after a minor stroke or high-risk TIA. The Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial enrolled patients at 114 sites in China from October 1, 2009, to July 30, 2012. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial enrolled patients at 269 international sites from May 28, 2010, to December 19, 2017. Both were followed up for 90 days. Data analysis occurred from November 2018 to May 2019. INTERVENTIONSIn the 2 trials, patients with minor stroke or high-risk TIA were randomized to clopidogrel-aspirin or aspirin alone within 12 hours (POINT) or 24 hours (CHANCE) of symptom onset. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was a major ischemic event (ischemic stroke, myocardial infarction, or death from ischemic vascular causes). The primary safety outcome was major hemorrhage. RESULTSThe study enrolled 5170 patients (CHANCE) and 4881 patients (POINT). Analysis included individual data from 10 051 patients (5016 in the clopidogrel-aspirin treatment group and 5035 in the control group) with a median age of 63.2 (interquartile range, 55.0-72.9) years; 6106 patients (60.8%) were male. Clopidogrel-aspirin treatment reduced the risk of major ischemic events at 90 days compared with aspirin alone (328 of 5016 [6.5%] vs 458 of 5035 [9.1%]; hazard ratio [HR], 0.70 [95% CI, 0.61-0.81]; P < .001), mainly within the first 21 days (263 of 5016 [5.2%] vs 391 of 5035 [7.8%]; HR, 0.66 [95% CI, 0.56-0.77]; P < .001), but not from day 22 to day 90. No evidence of heterogeneity of treatment outcome across trials or prespecified subgroups was observed. Major hemorrhages were more frequent in the clopidogrel-aspirin group, but the difference was nonsignificant. CONCLUSIONS AND RELEVANCEIn this analysis of the POINT and CHANCE trials, the benefit of dual antiplatelet therapy appeared to be confined to the first 21 days after minor ischemic stroke or high-risk TIA.

Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis

“…An important proportion of patients with ischaemic cerebrovascular disease (CVD) are not protected from recurrent vascular events with commonly prescribed 'non-monitored' antiplatelet therapy. Because the risk of recurrent events is highest early after a non-cardioembolic TIA/ischaemic stroke [1,2], early institution of an effective preventive antiplatelet regimen is very important [3].…”

Ticagrelor vs Clopidogrel in addition to Aspirin in minor ischemic stroke/ transient ischemic attack—Protocol for a systematic review and network meta-analysis

“…The primary outcome of interest will be recurrent ischemic stroke (Time-To-Event) up to 30 days. 30 days was chosen as the primary outcome because the majority of recurrent ischemic stroke events in this population occur within the first 21 days; data from trials investigating DAPT in this population have found that DAPT does not significantly reduce stroke risk during days 22–90 [ 18 ]. Time-To-Event (TTE) data will be presented as hazard ratios within intention-to-treat populations with 95% confidence intervals.…”

Transocular sonography in acute arterial occlusions of the eye in elderly patients: Diagnostic value of the spot sign

“…Although most CRAO are assumed to have an arterial source of embolism, ipsilateral highgrade carotid artery stenosis is found in only a minority of these patients. In patients with CRAO and non-stenotic arteriosclerotic lesions of the supraaortic arteries, short time (21 days) dual antiplatelet therapy may be beneficial (analogous to data on patients with minor ischemic stroke and transient ischemic attack) [20]. Whether the antithrombotic treatment strategy should be influenced by the presence or absence of the spot sign (e.g., antiplatelet therapy vs. oral anticoagulation) is unclear.…”