Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point–Blinded, Noninferiority Trial

Abstract

Background: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care following percutaneous coronary intervention (PCI). However, some adverse non-cardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retain the antithrombotic efficacy, but its combination with a P2Y12 inhibitor is still lack of randomized clinical trial (RCT) evidence. Methods: In this randomized, open-label, non-inferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent (DES) implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75mg/d for 12 months) or conventional DAPT (aspirin 100mg/d plus clopidogrel 75mg/d for 12 months). The primary endpoint was a 1-year composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), ischemic stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) criteria type 2, 3 or 5 bleeding. The endpoints were adjudicated by an independent Clinical Event Committee. Results: Between January 11, 2018 and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary endpoint occurred in 101 (4.47%) patients in the indobufen-based DAPT group and 140 (6.11%) patients in the conventional DAPT group (absolute difference -1.63%, pnon-inferiority <0.001; hazard ratio (HR) 0.73, 95% CI 0.56 to 0.94, p=0.015). CV death, nonfatal MI, ischemic stroke and ST were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group, and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all p>0.05). The occurrence of BARC criteria type 2, 3 or 5 bleeding events was lower in the indobufen-based DAPT group compared to the conventional DAPT group (2.97% vs 4.71%, HR 0.63, 95%CI 0.46 to 0.85, p=0.002), with main decrease in type 2 bleeding (1.68% vs 3.49%, HR 0.48, 95%CI 0.33 to 0.70, p<0.001). Conclusions: In Chinese patients with negative cardiac troponin undergoing DES implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was mainly driven by a reduction in bleeding events without an increase in ischemic events.

Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry

“…Although previous studies observed that indobufen effectively prevented the ischemic events after coronary artery bypass grafting [ 24 ] and cerebral infarction [ 25 ], few studies focus on the performance of indobufen based DAPT on clinical events after PCI. The OPTION trial, initiated by our cardiac center, is considered the largest multicenter randomized controlled trial so far to compare the efficacy and safety of indobufen versus aspirin in patients requiring DAPT [ 5 ]. However, this trial only focused on patients with negative cardiac troponin, and those with aspirin intolerance were also excluded due to ethical considerations.…”

“…However, there are still few large-scale studies focused on the efficacy and safety of indobufen based DAPT. The OPTION study is so far the largest multicenter randomized controlled trial to compare the performance of indobufen versus aspirin in patients requiring DAPT, whose encouraging results have been published recently [ 5 ]. Nevertheless, this trial excluded the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance.…”

Pan-vascular disease: what we have done in the past and what we can do in the future?

“…The management of residual thrombus risk is crucial in patients with pan-vascular disease, necessitating navigation through the complex interplay among coagulation, platelets, and inflammation. Our latest OPTION study introduces indolibuprofen as a safe and effective option for stable coronary artery disease, suggesting its potential as a dual-channel antithrombotic therapy for high-risk ischemic but low-bleeding risk patients [31][32][33][34] .…”

Chinese expert consensus on anti-thrombotic therapy for pan-vascular diseases (2023 edition)

“…It is recommended that patients with CCS take aspirin 75 to 100 mg daily. For those who are intolerant to aspirin, indobufen or clopidogrel can be used instead [4,[54][55] . For CCS patients undergoing percutaneous coronary intervention (PCI), it is recommended to refer to the 2018 Guidelines for the Diagnosis and Treatment of Stable Coronary Heart Disease for post-PCI DAPT [56] .…”