Indobufen not noninferior vs. aspirin for secondary prevention of ischemic stroke
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Results of the INSURE trial were unable to establish noninferiority of indobufen vs. aspirin for the secondary prevention of 90-day stroke in patients with moderate to severe ischemic stroke presenting within 72 hours of symptom onset.
Safety outcomes were not significantly different between the indobufen and aspirin groups, according to findings presented at the International Stroke Conference.
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“Dual therapy, mainly with clopidogrel plus aspirin, is the major recommended strategy for the current acute treatment of minor stroke and [transient ischemic attack] based on the CHANCE, POINT and THALES trials. However, for those with moderate to severe ischemic stroke, aspirin is the most evidence-based antiplatelet agent and currently recommended in the U.S. and Chinese guidelines. However, aspirin may lead to gastrointestinal intolerance and bleeding and alternative therapy is often considered,” Yunyun Xiong, MD, PhD, of the Beijing Tiantan Hospital, Capital Medical University, China, said during a presentation. “Indobufen is an old drug ... it's also a Cox inhibitor. It can inhibit platelet aggregation and prevent thrombosis. The anti-aggregation effect of indobufen subsides within 24 hours after administration of the drug. Its half-life is 7 hours, which may cause a lower risk of bleeding. Studies have shown that indobufen was comparable to aspirin in the treatment of ischemic heart disease and in China it has already received the indication for ischemic heart disease as well in Italy.”
The objective of the INSURE trial was to evaluate the noninferiority of indobufen compared with aspirin to reduce 3-month stroke risk for patients aged 18 to 80 years with moderate to severe ischemic stroke.
INSURE was an investigator-initiated, multicenter, double-blind, randomized controlled trial in which 5,438 patients (mean age, 64 years; 35% women) were assigned to either indobufen 100 mg plug aspirin placebo or aspirin 100 mg plus indobufen placebo within 72 hours of symptom onset for 90 days.
The primary outcome was new ischemic stroke at 90 days. The secondary outcomes included new stroke at 1 year. The safety outcomes included severe to moderate bleeding and mortality within 3 months and between 3 months and 1 year.
Xiong stated that the margin for noninferiority was a HR of 1.25.
Baseline characteristics were similar between indobufen and aspirin groups.
The primary outcome occurred in 7.9% of the indobufen group and 6.4% of the aspirin group.
Xiong stated that since the upper limit of the 95% CI was larger than the noninferiority margin, noninferiority of indobufen could not be established (HR for the primary outcome = 1.24; 95% CI, 1.01-1.52; HR for the secondary outcome of new stroke at 1 year = 1.17; 95% CI, 0.99-1.4; P = .07). A per-protocol analysis of the primary outcome did not change the results.
Although occurrence of safety outcomes was numerically lower in the indobufen arm, the differences were not statistically significant (P > .05 for all outcomes), according to the presentation.
The results did not differ according to prespecified subgroups.
“In patients with moderate to severe ischemic stroke within 72 hours after symptom onset, indobufen was not noninferior to aspirin in reducing the risk of subsequent stroke, and the safety profiles between these two treatments were similar with numerically fewer moderate or severe bleeding observed in the indobufen group,” Xiong said. “In clinical practice, it means that indobufen was not noninferior to aspirin, but we cannot either say it's inferior or superior. To test the inferiority or superiority of indobufen vs. aspirin, we still need further clinical trials.”
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Xiong Y, et al. LB13. Presented at: International Stroke Conference; Feb. 8-10, 2023; Dallas (hybrid meeting).
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