18 Jun 2021
Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial
Selected in The Lancet by D. Giacoppo
The HOST-EXAM trial sought to define whether, after DAPT for PCI with DES, clopidogrel monotherapy is associated with improved outcomes compared with aspirin monotherapy.
References
Authors
Bon-Kwon Koo, Jeehoon Kang, Kyung Woo Park, Tae-Min Rhee, Han-Mo Yang, Ki-Bum Won, Seung-Woon Rha, Jang-Whan Bae, Nam Ho Lee, Seung-Ho Hur, Junghan Yoon, Tae-Ho Park, Bum Soo Kim, Sang Wook Lim, Yoon Haeng Cho, Dong Woon Jeon, Sang-Hyun Kim, Jung-Kyu Han, Eun-Seok Shin, Hyo-Soo Kim, HOST-EXAM investigators
Reference
https://doi.org/10.1016/S0140-6736(21)01063-1
Published
May 16, 2021
Link
Read the abstractReviewer
My Comment
Why this study? – the rationale/objective
Some recent investigations have hypothesized that after dual antiplatelet therapy (DAPT) for percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation, interruption of aspirin and continuation of the P2Y12 inhibitor may be associated with significant benefits, as compared with traditional aspirin chronic maintenance. However, thus far, no randomized clinical trial has provided data related to the head-to-head comparison between aspirin and P2Y12 inhibitor monotherapies.
The HOST-EXAM trial sought to define whether after DAPT for PCI with DES clopidogrel monotherapy is associated with improved outcomes compared with aspirin monotherapy.
How was it executed? – the methodology
The HOST-EXAM is an investigator-initiated, prospective, randomized, open-label trial conducted at 37 sites in South Korea. Following an uneventful period of 6 to 18 months of DAPT after PCI with DES implantation, by web-based application, patients were randomly assigned in a 1:1 ratio to either clopidogrel 75 mg once daily, or aspirin 100 mg once daily. No restriction regarding clinical characteristics, presentation at the index PCI period, stenosis location and length, and number of lesions and vessels diseased were imposed. Key exclusion criteria were active bleeding, bleeding diathesis, history of major bleeding resulting in stop of antiplatelet agents within 3 months, known coagulopathy, refusal of blood transfusion, history of hypersensitivity or contraindication to aspirin or clopidogrel, and co-administration of another P2Y12 inhibitor or an anticoagulant agent.
The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding defined as Bleeding Academic Research Consortium (BARC) ≥ 3 type. The thrombotic composite endpoint included all the outcomes of the primary endpoint, with the exception of major bleeding.
What is the main result?
Between March 2014 and May 2018, a total of 5,438 patients without clinical events within 6-18 months following PCI with DES were randomly assigned to aspirin (2,728 - 50.2 %) or clopidogrel monotherapy (2,710 - 49.8 %). The DAPT regimen before randomization was mainly aspirin plus clopidogrel (4,430 patients - 81.5 %).
The mean age was 63.5 ± 10.7 years, 1,384 patients (25.5 %) were female, and 1,860 patients (34.2 %) had diabetes. The clinical diagnosis at the time of PCI was stable angina in 1,389 patients (25.5 %), unstable angina in 1,934 patients (35.5 %), non-ST segment elevation myocardial infarction in 1,054 patients (19.4 %), and ST segment elevation myocardial infarction in 933 patients (17.2 %). A total of 955 patients (18.3 %) had angiographically-diagnosed three-vessel disease and 272 patients (5.0 %) left main disease.
The median time from PCI to randomization was 382 [357–422] days. During the follow-up period, 35 patients (0.6 %) switched antiplatelet therapy outside the allocated treatment, 9 patients (0.2 %) withdrew informed consent, and 91 (1.7 %) were lost to follow-up. The allocated treatment discontinuation rates over follow-up were similar between treatment groups (5.1 % vs 4.9 %).
During the 24 months of follow-up, the primary net composite endpoint occurred in 152 patients (5.7 %) assigned to clopidogrel and in 207 patients (7.7 %) assigned to aspirin (HR 0.73, 95 % CI 0.59-0.90, p = 0.003). The thrombotic endpoint occurred in 99 patients (3.7 %) assigned to clopidogrel and in 146 patients (5.5 %) assigned to aspirin (HR 0.68, 95 % CI 0.52-0.87, p = 0.003). BARC ≥ 3 type events occurred in 33 patients (1.2 %) assigned to clopidogrel and in 53 patients (2.0 %) assigned to aspirin (HR 0.63, 95 % CI 0.41-0.97, p = 0.036).
No significant differences in all-cause death (HR 1.43, 95 % CI 0.93-2.19, p = 0.101), cardiac death (HR 1.37, 95 % CI 0.69-2.73, p = 0.374), non-fatal myocardial infarction (HR 0.65, 95 % CI 0.36-1.17, p = 0.150), definite or probable stent thrombosis (HR 0.63, 95 % CI 0.29-1.39, p = 0.251), target lesion revascularization (HR 0.67, 95 % CI 0.40-1.12, p = 0.130), target vessel revascularization (HR 0.78, 95 % CI 0.50-1.19, p = 0.245), and any repeat revascularization (HR 0.82, 95 % CI 0.57-1.16, p = 0.261) were observed between treatment groups.
However, treatment with clopidogrel was associated with significant reductions in stroke (18 patients, 0.7 %, vs. 43 patients, 1.6 %; HR 0.42, 95 % CI 0.24-0.73, p = 0.002), hemorrhagic stroke (4 patients, 0.2 %, versus 17 patients, 0.6 %; HR 0.24, 95 % CI 0.08-0.70, p = 0.010), readmission due to acute coronary syndrome (66 patients, 2.5 %, vs. 109 patients, 4.1 %; HR 0.61, 95 % CI 0.45-0.82, p = 0.001), and BARC ≥ 2 type events (61 patients, 2.3 %, vs. 87 patients, 3.3 %; HR 0.70, 95 % CI 0.51-0.98, p = 0.036) compared with aspirin. Of note, any minor gastrointestinal symptoms was less frequent in patients assigned to clopidogrel compared with those assigned to aspirin (272 patients, 10.2 %, vs. 320 patients, 11.9 %; HR 0.85, 95 % CI 0.72-1.00; p = 0.048).
No significant interaction between treatment effect and main settings was observed. Results of per-protocol analyses were consistent with those of intention-to-treat analyses.
Critical reading and the relevance for clinical practice:
The HOST-EXAM is the first large-scale randomized trial comparing clopidogrel with aspirin as chronic maintenance antithrombotic monotherapy after 6 to 18 months of DAPT for PCI with DES implantation.
The trial shows that chronic maintenance with clopidogrel significantly reduces at 24 months the incidence of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding compared with aspirin. Interestingly, the benefit seems to be driven by significant reductions in both thrombotic events, mainly stroke and readmission for acute coronary syndrome, and major bleeding. The distribution of events over follow-up time began to diverge approximately 9 months following randomization. The reasons for these trends are unclear.
In addition, although the study has no statistical power for individual endpoints, no consistent significant reduction in major coronary-related events, primarily myocardial infarction and repeat revascularization, was observed. Similarly, clopidogrel did not reduce cardiovascular death or was associated with a numerical decrease compared with aspirin.
By considering the higher anti-thrombotic effectiveness of clopidogrel compared with aspirin, the elucidation of the mechanisms leading to the significant benefits in terms of BARC ≥ 3 type and BARC ≥ 2 type at 24 months requires further analyses. This would be important bearing in mind that previous studies comparing P2Y12 inhibitor with aspirin as maintenance antithrombotic therapy in other settings have not shown significant difference in major and any bleeding between treatment groups. Moreover, although a direct link between survival and major bleeding has been demonstrated in other settings, in the present trial all-cause death was not significantly different between treatment groups.
In conclusion, the relevant results of the HOST-EXAM trial support the use of clopidogrel as chronic maintenance antithrombotic therapy after PCI with DES implantation. However, larger trials to validate or disprove main conclusions are warranted.
1 comment
support the use of aspirin as chronic maintenance antithrombotic therapy after PCI with DES implantation，we always do in practice.