Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–Extended Antiplatelet Monotherapy - HOST-EXAM

Dec 20, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
Date Presented:
05/16/2021
Date Published:
11/27/2024
Date Updated:
12/20/2024
Original Posted Date:
05/16/2021
References

Contribution To Literature:

Highlighted text has been updated as of December 20, 2024.

The HOST-EXAM trial showed that clopidogrel monotherapy is superior to aspirin monotherapy as chronic maintenance therapy among patients who had successfully completed the required duration of DAPT therapy post–DES PCI.

Description:

The goal of the trial was to assess the safety and efficacy of clopidogrel vs. aspirin monotherapy among patients who had completed the required duration of dual antiplatelet therapy (DAPT) post–drug-eluting stent (DES) percutaneous coronary intervention (PCI).

Study Design

Patients were randomized in a 1:1 open-label fashion to either clopidogrel monotherapy (n = 2,710) or aspirin (n = 2,728).

  • Total screened: 5,530
  • Total number of enrollees: 5,438
  • Duration of follow-up: 24 months
  • Mean patient age: 63.5 years
  • Percentage female: 25%

Inclusion criteria:

  • Age ≥20 years
  • Maintenance of DAPT for 12 ± 6 months post–DES PCI
  • No history of clinical events since PCI

Exclusion criteria:

  • Hypersensitivity or contraindication to medications
  • Patients with any major or active pathologic bleeding or known bleeding diathesis
  • Women of childbearing potential
  • Presence of noncardiac comorbid conditions with life expectancy <1 year

Other salient features/characteristics:

  • Diabetes mellitus: 34%
  • Previous myocardial infarction (MI): 16%
  • Index PCI: non–ST-segment elevation MI (NSTEMI): 19.4%, STEMI: 17.2%, stable angina: 25.6%, unstable angina: 36%
  • Three-vessel disease: 18%, left main PCI: 5%, chronic total occlusion PCI: 9%
  • Total stented length: 36 mm

Principal Findings:

The primary endpoint of all-cause mortality, MI, stroke, readmission due to acute coronary syndrome (ACS), major bleeding, for clopidogrel vs. aspirin, was 5.7% vs. 7.7% (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.90, p = 0.003).

  • All-cause mortality: 1.9% vs. 1.3% (p = 0.1)
  • Non-fatal MI: 0.7% vs. 1.0% (p = 0.15)
  • Stroke: 0.7% vs. 1.0% (p = 0.002)
  • ACS readmission: 2.5% vs. 4.1% (p = 0.001)

Secondary outcomes:

  • Thrombotic composite outcome (cardiovascular death, MI, stroke, ACS readmission, stent thrombosis): 3.7% vs. 5.5% (p = 0.003)
  • Any bleeding: 2.3% vs. 3.3% (p = 0.003)

Extended follow-up (median duration of follow-up: 5.8 years):

  • Primary endpoint for clopidogrel vs. aspirin: 12.8% vs. 16.9% (HR 0.74, 95% CI 0.63-0.86, p < 0.001)
  • Composite of cardiac death, nonfatal MI, ischemic stroke, readmission due to acute coronary syndrome, and definite or probable stent thrombosis: 8.1% vs. 11.9% (p < 0.001)
  • Bleeding Academic Research Consortium (BARC) ≥2 bleeding: 4.5% vs. 6.1% (p = 0.016)
  • All-cause mortality: 6.2% vs. 6.0% (p = 0.74)
  • Nonfatal MI: 1.6% vs. 2.3% (p = 0.1)
  • Definite or probable stent thrombosis: 0.5% vs. 0.7% (p = 0.28)
  • Benefits for the primary endpoint were sustained on landmark analysis at 2 years

High bleeding risk (HBR) and complex PCI: HBR was noted in 21.8% of patients (468 in clopidogrel vs. 398 in aspirin arm). Coprimary endpoints occurred more frequently in the HBR group than the non-HBR group. Complex PCI was pursued in 21.4% of patients (441 in clopidogrel vs. 408 in aspirin arm). No statistical difference was found in the incidence of the coprimary endpoints between the complex and noncomplex PCI groups. No significant interactions were found between the treatment arms and the presence of HBR or PCI complexity for the coprimary endpoints and individual components of the composite endpoints or revascularization (p for interaction for all > 0.05).

Interpretation:

The results of this trial indicate that clopidogrel monotherapy is superior to aspirin monotherapy as chronic maintenance therapy among patients who had successfully completed the required duration of DAPT therapy post–DES PCI. Benefits were noted in thrombotic and bleeding events. On extended follow-up, the benefit of clopidogrel over aspirin was sustained out to a median of 5.8 years. Bleeding was also lower with clopidogrel, although MI and stent thrombosis were similar. The effect of clopidogrel over aspirin was similar among HBR or complex PCI subsets. 

One caveat is that these were all East Asian patients, and clopidogrel resistance was not assessed. It is unclear if clopidogrel would have the same efficacy among similar patients in the United States.

We have seen several interesting trials in the DAPT space in the past few years. Trials such as TWILIGHT have shown that it may be possible to continue ticagrelor monotherapy and drop aspirin after 3 months with no penalty in ischemic outcomes and a reduction in bleeding outcomes among patients undergoing PCI. Similarly, STOPDAPT-2 suggested that clopidogrel monotherapy could be continued after 1 month in patients undergoing PCI for stable ischemic heart disease and ACS. In the current trial, all-cause mortality was numerically higher with clopidogrel; further long-term follow-up will be important. A similar signal for higher mortality, especially noncardiovascular mortality, was noted in the DAPT trial among patients receiving extended-duration DAPT 12 months post-PCI. However, bleeding was lower in this trial, not higher, as noted in the DAPT trial.

References:

Kang J, Chung J, Park KW, et al. Long-Term Aspirin vs Clopidogrel After Coronary Stenting by Bleeding Risk and Procedural Complexity. JAMA Cardiol 2024;Nov 27:[Epublished].

Kang J, Park KW, Lee H, et al. Aspirin vs. Clopidogrel for Chronic Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study. Circulation 2023;147:108-17.

Koo BK, Kang J, Park KW, et al., on behalf of the HOST-EXAM Investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomized, open-label, multicenter trial. Lancet 2021;397:2487-96.

Presented by Dr. Hyo-Soo Kim at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 16, 2021.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: ACC21, ACC Annual Scientific Session, Acute Coronary Syndrome, Aspirin, Drug-Eluting Stents, Hemorrhage, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Thrombosis


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