HOST-EXAM trial

HOST-EXAM trial

HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy) trial was an investigator initiated, prospective, randomized, open label multi centre trial [1]. The study had 37 sites in South Korea. It was a head to head comparison of efficacy and safety of aspirin and clopidogrel as monotherapy during chronic maintenance therapy in patients who underwent coronary stenting.

The highlight of the HOST-EXAM trial was that it showed that clopidogrel monotherapy was superior to aspirin monotherapy as chronic maintenance therapy among patients who have completed the required dual anti platelet therapy after percutaneous coronary intervention (PCI) with drug eluting stent (DES) implantation.

The study enrolled patients who were on dual antiplatelet therapy for 6-18 months after PCI with DES without clinical events. Those who had any ischemic or major bleeding complications were excluded. Patients were randomly assigned to clopidogrel 75 mg or aspirin 100 mg once daily for 24 months. Primary composite end point included all cause mortality, non fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and BARC (Bleeding Academic Research Consortium) bleeding type 3 or greater. It was an intention to treat analysis.

5438 patients were randomized and ascertainment of the primary endpoint was completed in 5338 patients. Primary outcome occurred in 5·7% patients in the clopidogrel group and 7·7% in the aspirin group (p=0·0035). All cause mortality was 1.9% in clopidogrel group vs 1.3% in aspirin group, which was not statistically significant. Non fatal myocardial infarction was 0.7% vs 1.0% which was also not significant. Stroke occurred in 0.7% of the clopidogrel group and 1.0% of the aspirin group, which was statistically significant (p = 0.002). Readmission with acute coronary syndrome (ACS) was 2.5% vs 4.1%, which was also statistically significant (p = 0.001).

Secondary thrombotic outcome was a composite of cardiovascular death, myocardial infarction, readmission for ACS and stent thrombosis. It was 3.7% in clopidogrel group vs 5.5% in aspirin group (p = 0.003). Secondary bleeding outcome was any bleeding, which was 2.3% with clopidogrel and 3.3% with aspirin (p = 0.003).

The authors concluded that in patients requiring indefinite antiplatelet monotherapy after PCI, clopidogrel monotherapy was superior to aspirin in preventing future adverse events.

Limitations

One important limitation while generalizing the data for global population is the geographic limit of the study which was conducted in one country. Open label nature of the study is another obvious disadvantage. Clopidogrel resistance was not assessed in the study. This study is definitely hypothesis generating and calls for a multi national, double blind comparison on a larger scale to get a better conclusion on long term antiplatelet monotherapy after PCI with DES. 

AUGUSTUS trial

A somewhat similar disadvantage for aspirin was suggested in the AUGUSTUS trial among patients with atrial fibrillation and recent ACS or PCI [2]. Adding apixaban to P2Y₁₂ inhibitor resulted in lower bleeding compared with vitamin K antagonist and a lower rate of death or rehospitalization. Addition of aspirin resulted in greater bleeding without any difference in efficacy. 92.6% of the patients in that study was on clopidogrel at randomization, while only 1.1% was on prasugrel and 6.2% on ticagrelor. But in the AUGUSTUS trial, there was no head to head comparison of aspirin vs clopidogrel or any other P2Y₁₂ inhibitor. There was an aspirin vs placebo comparison while there was no P2Y₁₂ inhibitor vs placebo comparison.

References

1. Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS; HOST-EXAM investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet. 2021 May 14:S0140-6736(21)01063-1.
2. Alexander JH, Wojdyla D, Vora AN, Thomas L, Granger CB, Goodman SG, Aronson R, Windecker S, Mehran R, Lopes RD. Risk/Benefit Tradeoff of Antithrombotic Therapy in Patients With Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From AUGUSTUS. Circulation. 2020 May 19;141(20):1618-1627.