Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury - OPT-PEACE

Nov 06, 2021
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
China national key R&D project, Ankon Medical Technologies (Shanghai, China)
Date Presented:
11/06/2021
Date Published:
11/06/2021
Date Updated:
11/06/2021
Original Posted Date:
11/06/2021
References

Contribution To Literature:

The OPT-PEACE trial showed that among low bleeding risk patients who had successfully completed 6 months of DAPT post-PCI and without evidence of a GI ulcer at that time, gastric or small intestinal mucosal injury was lower with SAPT (aspirin or clopidogrel) compared with DAPT (aspirin + clopidogrel).

Description:

The goal of the trial was to demonstrate the gastrointestinal (GI) safety of an additional 6 months of single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT) among low bleeding risk patients who had undergone percutaneous coronary intervention (PCI) and had no evidence of GI injury on magnetic capsule endoscopy at 6 months.

Study Design

All patients underwent capsule endoscopy after 6 months of DAPT. Patients without a GI ulcer were randomized in a 1:1:1 fashion to receive either aspirin 100 mg/day + placebo (n = 168), clopidogrel 75 mg/day + placebo (n = 169), or aspirin 81 mg daily + clopidogrel 75 mg daily (n = 168) for an additional 6 months.

  • Total screened: 1,092
  • Total number of enrollees: 505
  • Duration of follow-up: 1 year
  • Mean patient age: 57 years
  • Percentage female: 26%

Inclusion criteria:

  • Adult patients ages 18-80 years
  • Presentation with silent ischemia, stable angina, or non–ST-segment elevation acute coronary syndrome with GRACE score <140 at admission
  • PCI with implantation of contemporary drug-eluting stent(s) during the present admission
  • Complete revascularization (successful PCI treatment of all epicardial coronary lesions with diameter stenosis >70% or intermediate lesions with fractional flow reserve ≤0.8)
  • Planned DAPT with aspirin and clopidogrel for at least 6 months
  • ANKON capsule endoscopy successfully completed (visualization of the entire upper gastrointestinal tract and small intestine) demonstrating no ulceration or active bleeding (erosions were permitted)

Exclusion criteria:

  • High bleeding risk
  • ST-segment elevation myocardial infarction (STEMI) presentation
  • Age >80 years
  • Baseline anemia or thrombocytopenia
  • Planned use of a proton-pump inhibitor, gastric mucosa protectant, or any other antacid agent after study enrollment
  • Prior GI bleeding or ulcers within 24 months
  • Severe chronic kidney disease
  • Need for oral anticoagulant
  • Left main stenosis >30%, prior PCI within 1 year, prior stent thrombosis
  • Contraindications to the capsule endoscopy test
  • Left ventricular ejection fraction (LVEF) <40%

Other salient features/characteristics:

  • Active smoking: 35%
  • Unstable angina presentation: 82%, NSTEMI: 12%
  • LVEF: 62.5%
  • Hemoglobin: 14.1 g/dl
  • Helicobacter pylori (H. pylori) positive: 28%

Principal Findings:

The primary outcome, gastric or small intestinal injury on magnetic capsule endoscopy at 12 months, for aspirin monotherapy vs. clopidogrel monotherapy vs. DAPT, was: 92.4% vs. 96.2% vs. 99.2% (p = 0.18 for aspirin vs. clopidogrel; p = 0.02 for SAPT vs. DAPT). This was largely due to worsening in existing erosions.

  • Ulceration: 13.6% vs. 15.2% vs. 18.5% (p = 0.73 for aspirin vs. clopidogrel; p = 0.3 for SAPT vs. DAPT)
  • Bleeding: 0%

Secondary outcomes for aspirin monotherapy vs. clopidogrel monotherapy vs. DAPT:

  • Bleeding Academic Research Consortium (BARC) type 1 bleeding: 3.6% vs. 7.7% vs. 9.5% (p > 0.05)
  • GI bleeding: 0% vs. 1.2% vs. 5.4% (p = 0.5 for aspirin vs. clopidogrel; p = 0.01 for SAPT vs. DAPT)
  • Target lesion failure (cardiac death, target-vessel MI, target lesion revascularization): 0%

Interpretation:

The results of this trial indicate that among low bleeding risk patients who had successfully completed 6 months of DAPT post-PCI and without evidence of a GI ulcer at that time, gastric or small intestinal mucosal injury was extremely common (>90%) with aspirin, clopidogrel, and aspirin + clopidogrel; SAPT had lower rates compared with DAPT. These results were somewhat more pronounced among patients without evidence of any erosions after 6 months of DAPT. The GI endpoint was mostly driven by worsening erosions; new ulceration and bleeding rates were comparable.

GI side effects are generally felt to be higher with aspirin compared with clopidogrel, but in this trial, no differences were noted between the two agents when used as monotherapy. On sensitivity analysis, patients without any erosions at 6 months were more likely to develop new mucosal injury after an additional 6 months with clopidogrel compared with aspirin. An important limitation is that data on concomitant nonsteroid anti-inflammatory agent use were not available. These are also all East Asian patients; the generalizability to other racial and ethnic populations is unclear. Studies are also needed to determine whether prophylactic administration of an H2-blocker or proton-pump inhibitor medication or more frequent H. pylori eradication therapy would be beneficial in this patient population.

References:

Han Y, Liao Z, Li Y, et al. Magnetically-Controlled Capsule Endoscopy for Assessment of Antiplatelet Therapy-Induced Gastrointestinal Injury. J Am Coll Cardiol 2021;Nov 5:[Epub ahead of print].

Editorial Comment: Bittl J. Gastrointestinal Injury Caused by Aspirin or Clopidogrel Monotherapy Versus Dual Antiplatelet Therapy. J Am Coll Cardiol 2021;Nov 5:[Epub ahead of print].

Presented by Dr. Yaling Han at the Transcatheter Cardiovascular Therapeutics (TCT) Conference, Orlando, FL, November 6, 2021.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and SIHD, Interventions and ACS, Interventions and Vascular Medicine, Chronic Angina

Keywords: Acute Coronary Syndrome, Angina, Stable, Angina, Unstable, Aspirin, Capsule Endoscopy, Clopidogrel, Constriction, Pathologic, Drug-Eluting Stents, Fractional Flow Reserve, Myocardial, Gastrointestinal Hemorrhage, Helicobacter pylori, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Proton Pump Inhibitors, Secondary Prevention, ST Elevation Myocardial Infarction, TCT21, Transcatheter Cardiovascular Therapeutics, Ulcer, Upper Gastrointestinal Tract


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