The researches find that the dual antiplatelet therapy with clopidogrel and aspirin resulted in a net benefit vs aspirin alone when balancing the risks of a recurrent stroke against a hemorrhagic event; pooled data from two randomized, double-blind studies suggests. The analysis used individual patient-level data on more than 10,000 participants in the previously reported CHANCE and POINT trials; both comparing a combination of clopidogrel and aspirin with aspirin alone.
The dual antiplatelet therapy
“Patients with minor acute ischemic stroke and high-risk TIA benefit from treatment with clopidogrel–aspirin,” study author Claiborne Johnston, MD, PhD, dean and vice president for medical affairs at the Dell Medical School of the University of Texas at Austin, told Medscape Medical News. “This secondary analysis suggests 21 days may be the optimal duration of treatment to maximize benefit in reduction of ischemic events and minimize risk of hemorrhage;” he added.
The study was published online August 19 in JAMA Neurology. These same researchers conducted the individual trials included in the latest report. The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study showed a 32% lower risk of stroke recurrence among Chinese people treated within 24 hours with a combination of clopidogrel and aspirin vs aspirin alone. The study also showed no increase in the risk of hemorrhagic complications, as previously reported by Medscape Medical News.
A second study; the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial; also favored clopidogrel plus aspirin vs aspirin alone in an international patient population. “However, an increase in major hemorrhage observed in the POINT trial led to concerns about bleeding risks in dual antiplatelet therapy;” the researchers note. “Uncertainties remained about the risks and benefits of dual antiplatelet therapy and the optimal duration of dual antiplatelet therapy for minor stroke or TIA;” they add. “Moreover, the two trials were each moderate in size, whereas pooled-data analysis can provide more precise estimates of treatment outcomes.”
A total of 0.6% participants experienced major hemorrhage in the dual antiplatelet group vs 0.4% in the aspirin monotherapy group (adjusted HR, 1.59; 95% CI, 0.88 – 2.86). The difference was not statistically significant (P = .12). The rate of minor hemorrhage at 90 days was likewise higher in the clopidogrel–aspirin patients; 1.9% compared to 0.9% of the aspirin-only group (adjusted HR, 2.01; 95% CI, 1.41 – 2.86; P < .001). There were no significant differences between the two groups in the rates of hemorrhagic stroke or death from any cause.
“The absolute numbers of major ischemic events prevented by clopidogrel aspirin exceeded the increase in major hemorrhages; particularly within the first 3 weeks of treatment;” the researchers note. For example; within the first 21 days, those receiving clopidogrel–aspirin treatment experienced a significantly lower rate of major ischemic events, 5.2%, compared with 7.8% among others receiving aspirin alone (adjusted HR, 0.66; 95% CI, 0.56 – 0.77; P < .001).