OPT-BIRISK: Extended P2Y12 Monotherapy is Superior to Extended DAPT for High Risk ACS Patients

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By Lucas Marinacci on

Key Points

  • This trial randomizing patients at high bleeding and/or ischemic risk who had successfully completed 9-12 months of dual anti-platelet therapy (DAPT) following initial percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) to an additional 9 months of either continued DAPT or clopidogrel monotherapy plus placebo found that patients in the clopidogrel monotherapy arm had significantly lower rates of clinically relevant bleeding and major adverse cardiovascular and cerebral events (MACCE; defined as all-cause death, MI, stroke, and clinically indicated revascularization).
  • These data indicate that among patients at high bleeding and/or ischemic risk who undergo PCI for ACS, after initial 9-12 months of DAPT, de-escalation to clopidogrel alone is superior to continuation of DAPT for 9 additional months in terms of both bleeding and ischemia.
  • The exact duration of clopidogrel monotherapy following the initial 9-12 months of DAPT in these patients remains uncertain. When and if they should de-escalate to aspirin monotherapy or if they should remain on lifelong clopidogrel is an area of future research.

Recent guidelines indicate that following PCI for ACS, DAPT is recommended for 12 months, but shorter regiments are reasonable for patients at elevated bleeding risk and longer regimens are reasonable for those at elevated ischemic risk.1  What to do with the antithrombotic regimen with patients at high risk for both bleeding and ischemia, referred to as “bi-risk” patients, remains uncertain.

On August 28th, 2023 the results of the Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients (OPT-BIRISK) trial were presented in a Hot Line Session at ESC Congress 2023.

In this double-blinded clinical trial, patients across 101 centers in China who received PCI with drug-eluding stent (DES) placement for ACS and successfully completed 9-12 months of DAPT were randomized in a 1:1 fashion to either continued DAPT with aspirin and clopidogrel or clopidogrel alone with placebo for an additional 9 months.  Both arms were de-escalated to aspirin monotherapy for another three months thereafter.

Criteria for high bleeding risk included: age>= 75, female, iron deficiency anemia, history of stroke, medical treatment of diabetes, chronic kidney disease (CKD; eGFR <60 mL/min or creatinine clearance <60 mL/min).  Criteria for high ischemic risk included age >= 75 years, troponin positive ACS, multiple coronary lesions, stent length >30mm for target lesions, thrombotic target lesions, Medina 0, 1, 1 or 1, 1, and 1 for bifurcation lesions with stents in both main and side branch, left main >=50% or proximal left anterior descending > 70% stenosis, previous myocardial infarction, ischemic stroke, peripheral artery disease or peripheral or coronary revascularization, recurrent ischemic event in the prior 9 months, medical treatment for diabetes, or CKD.  Patients who were younger than 65 needed to meet at least one criteria in both categories, patients aged 65-75 needed to meet at least one criteria in either category.  Exclusion criteria included: DAPT termination in the prior 6 months for any reason, repeat revascularization in the last 90 days, hemodialysis, thrombocytopenia, hepatic insufficiency, planned upcoming surgery, and concomitant anticoagulation.

Overall, 7758 patients were enrolled and followed for 9 months.  The mean age was 65 years; 41% were female.  Patients in the clopidogrel plus placebo arm had significantly lower rates of the primary outcome of relevant bleeding defined as Bleeding Academic Research Consortium (BARC) 2, 3, or 5 at 9 months (2.5% vs. 3.3%, HR 0.75, 95% CI 0.57-0.96; p = 0.03) as well as  significantly lower rates of the key secondary outcome of MACCE (2.6% vs. 3.5%, HR 0.74, 95% CI 0.57-0.96; p = 0.02).  There was no significant difference in all cause death (0.3% vs 0.5%), myocardial infarction (0.4% vs. 0.7%), stroke (0.7% vs. 0.8%), clinically driven revascularization (1.4% vs. 1.8%), and stent thrombosis (0.05% vs. 0.03%) in the clopidogrel monotherapy vs. DAPT arm, respectively.

What to do longer term with these patients and how to manage those on concomitant anticoagulation remains uncertain. It is also unclear why ischemic events rates were lower in the monotherapy arm, although it should be noted that the upper limit of the confidence interval for the MACCE outcome approached unity, hence the possibility of no difference was within the range of plausible values.

According to principal investigator Ya-Ling Han of the General Hospital of Northern Theater Command, Shenyang, China: “In conclusion, for bi-risk ACS patients who completed 9-12 months of DAPT after DES implantation, a clopidogrel monotherapy regimen was superior to DAPT in reducing major bleeding and ischemic events.”

References

  1. Mourikis P, Polzin A. Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention: How Short Is Too Short? J Am Heart Assoc. 2023;12:10–12.