Optimal antiPlatelet Therapy for high Bleeding and Ischemic RISK patients - OPT-BIRISK

May 21, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
National Key R & D Project of China, Sanofi-Aventis Co. Ltd.
Date Presented:
08/28/2023
Date Published:
04/17/2024
Date Updated:
05/21/2024
Original Posted Date:
08/28/2023
References

Contribution To Literature:

Highlighted text has been updated as of May 21, 2024.

The OPT-BIRISK trial showed that among high bleeding and ischemic risk patients who had successfully completed 9-12 months of DAPT with aspirin and clopidogrel following DES PCI for an ACS presentation, clopidogrel monotherapy is superior to continued DAPT for an additional 9 months; reductions were noted in both ischemic and bleeding events.

Description:

The goal of the trial was to compare the safety and efficacy of clopidogrel monotherapy compared with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel as maintenance therapy after completion of 9-12 months of DAPT following drug-eluting stent (DES) percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).

Study Design

Eligible patients were randomized in a 1:1 double-blinded fashion to either clopidogrel monotherapy (n = 3,850) or continued DAPT with aspirin and clopidogrel (n = 3,850) for an additional 9 months following successful completion of 9-12 months of DAPT after initial PCI. Both arms were then switched to aspirin monotherapy for another 3 months.

  • Total number of enrollees: 7,758
  • Duration of follow-up: 9 months
  • Mean patient age: 65 years
  • Percentage female: 41%

Inclusion criteria:

  • ACS patients undergoing PCI (new-generation DES) and finishing 9-12 months of DAPT
  • Patients aged 18-85 years
  • Patients aged <65 years must meet at least one of the following clinical criteria of high bleeding risk and at least one of the following clinical criteria of high ischemic risk; patients aged 65-75 years must meet one of the following clinical criteria of either high bleeding risk or high ischemic risk

Clinical criteria of high bleeding risk:

    • ≥75 years old
    • Female
    • Iron deficiency anemia
    • History of stroke (hemorrhagic or ischemic)
    • Ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin)
    • Chronic kidney disease (eGFR <60 mL/min or creatinine clearance <60 mL/min)

Clinical criteria of high ischemic risk:

    • ≥75 years old
    • Multiple coronary lesions
    • Target lesions required for stent of total length >30 mm
    • Thrombotic target lesions
    • Bifurcation lesions are Medina 0, 1, 1 or 1, 1, and 1, with stents implanted in both main branch and side branch
    • Left main coronary artery (≥50%) or proximal LAD (≥70%) lesions
    • Calcified plaques requiring endovascular excision
    • ACS with troponin positive
    • Previous myocardial infarction (MI), ischemic stroke, diagnosed peripheral arterial disease (PAD), or revascularization due to coronary artery disease/PAD
    • Recurrent MI, revascularization, stent thrombosis, stroke in the last 9 months
    • Ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin)
    • Chronic kidney disease (eGFR <60 mL/min or creatinine clearance <60 mL/min)

Exclusion criteria:

  • Discontinuation or termination of DAPT treatment during the past 6 months due to adverse events (bleeding or ischemia) or other conditions
  • Surgery plan within 90 days
  • Coronary revascularization (surgical or intervention) program within 90 days
  • Dialysis-dependent renal failure
  • Moderate or severe hepatic insufficiency (2 times the upper limit of normal for ALT or AST)
  • Life expectancy <1 year
  • Unable or unwilling to provide informed consent
  • Women with childbearing potential
  • Platelet count <100,000/mm3
  • Subjects undergoing warfarin or similar anticoagulant therapy

Other salient features/characteristics:

  • Diabetes mellitus: 52.5%
  • Prior MI: 18%
  • Presentation: STEMI (21%), NSTEMI (25%).
  • Median GRACE score: 88
  • Number of stents per patient: 1.8

Principal Findings:

The primary endpoint, clinically relevant bleeding (Bleeding Academic Research Consortium [BARC] 2, 3, or 5) at 9 months for clopidogrel monotherapy vs. DAPT was: 2.5% vs. 3.3% (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.57-0.97, p = 0.03). BARC 3, 5 bleeding, was: 0.5% vs. 0.7% (p > 0.05).

Secondary outcomes for clopidogrel monotherapy vs. DAPT:

  • Major adverse cardiovascular and cerebrovascular events (all-cause death, MI, stroke, and clinically indicated revascularization): 2.6% vs. 3.5% (HR 0.74, 95% CI 0.57-0.96, p < 0.001 for noninferiority, p = 0.02 for superiority)
  • All-cause mortality: 0.3% vs. 0.5% (p = 0.38)
  • Ischemic stroke: 0.7% vs. 0.8% (p = 0.37)
  • Stent thrombosis: 0.05% vs. 0.03% (p = 0.57)

Interpretation:

The results of this trial indicate that, among high bleeding and ischemic risk patients who had successfully completed 9-12 months of DAPT with aspirin and clopidogrel following DES PCI for an ACS presentation, clopidogrel monotherapy is superior to continued DAPT for an additional 9 months; reductions were noted in both ischemic and bleeding events.

These are interesting and important results. In the DAPT trial, continuing DAPT beyond 12 months (up to 30 months) was superior to aspirin monotherapy for ischemic events but associated with a higher risk of bleeding. Studies indicate an overlap between patients with high bleeding and ischemic risk; the current trial suggests that clopidogrel monotherapy may be a better strategy for these patients for maintenance. The exact duration of treatment with clopidogrel (lifelong?) and its efficacy compared with aspirin for maintenance therapy is unclear, although there are increasing data to suggest that P2Y12 inhibitors may be better than aspirin for secondary prevention from a long-term perspective.

References:

Li Y, Li J, Wang B, et al. Extended Clopidogrel Monotherapy vs DAPT in Patients With Acute Coronary Syndromes at High Ischemic and Bleeding Risk: The OPT-BIRISK Randomized Clinical Trial. JAMA Cardiol 2024;Apr 17:[Epublished].

Editorial Comment: Valgimigli M, Landi A. Clopidogrel Monotherapy for Double-Risk Acute Coronary Syndrome. JAMA Cardiol 2024;Apr 17:[Epublished].

Presented by Dr. Yaling Han at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 28, 2023.

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

Keywords: Acute Coronary Syndrome, ESC Congress, ESC23, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation


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