Optimizing Antithrombotic Care in patients with AtriaL fibrillatiON and coronary stEnt - OAC-ALONE

Sep 24, 2018
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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:
Daiichi Sankyo
Date Presented:
09/24/2018
Date Published:
09/24/2018
Date Updated:
09/24/2018
Original Posted Date:
09/24/2018
References

Contribution To Literature:

Due to premature cessation of the OAC-ALONE trial, noninferiority of OAC alone could not be established compared with OAC + SAPT among patients with AF and stable CAD with remote PCI.

Description:

The goal of the trial was to evaluate the safety and efficacy of eliminating antiplatelet therapy among patients with atrial fibrillation (AF) also on oral anticoagulation (OAC) and stable coronary artery disease (CAD) who had received stents more than 1 year ago.

Study Design

Patients with stable CAD with percutaneous coronary intervention (PCI) >1 year ago and AF on OAC were randomized in a 1:1 fashion to either OAC + single antiplatelet therapy (SAPT) (n = 346) or OAC alone (n = 344). The trial was terminated early due to slow enrollment and lower than expected event rates.

  • Total number of enrollees: 696
  • Duration of follow-up: 2.5 years
  • Mean patient age: 75 years
  • Percentage female: 15%

Inclusion criteria:

  • Patients with a documented history of AF who underwent PCI with stenting >12 months before enrollment
  • Patients who are treated with OAC (warfarin or direct OAC [DOAC]) and an antiplatelet drug (aspirin or clopidogrel), but not with other antiplatelet drugs including ticlopidine, prasugrel, ticagrelor, and cilostazol
  • In patients treated with warfarin, the international normalized ratio (INR) value at enrollment should be ≥1.6, and agreement on dose adjustment of warfarin with the target INR range of 2.0-3.0 for those <70 years and 1.6-2.6 for those ≥70 years before enrollment
  • Patients ≥20 years

Exclusion criteria:

  • Patients who underwent PCI including balloon angioplasty alone within the past 12 months
  • Patients in whom OAC is scheduled to be discontinued during the follow-up period
  • Patients with a past history of stent thrombosis
  • Patients with a planned coronary revascularization
  • Patients with a planned cardiovascular or noncardiovascular surgery
  • Patients with expectation of survival <1 year

Other salient features/characteristics:

  • CHA2DS2-VASc score: 4.6
  • HAS-BLED score ≥3: 44%
  • AF: Paroxysmal: 43%, permanent: 49%
  • Number of stents: 2; type of stent: first-generation drug-eluting stent (DES): 23%, second-generation DES: 48%, bare-metal stent: 29%
  • Left main PCI: 6.5%, multivessel PCI: 35%
  • Years from last PCI: mean 4.6 years

Principal Findings:

The primary endpoint, all-cause mortality, myocardial infarction (MI), stroke, systemic embolism, for OAC + SAPT vs. OAC, was 13.6% vs. 15.7%, p for noninferiority = 0.20, p for superiority = 0.45.

Secondary outcomes for active assessment vs. control:

The composite of all-cause mortality, MI, stroke, systemic embolism, International Society on Thrombosis and Hemostasis (ISTH) major bleeding, was 19.4% vs. 19.5%, p for noninferiority: 0.016, p for superiority: 0.96.

  • All-cause mortality: 9.0% vs. 11.6%, p = 0.27
  • MI: 1.2% vs. 2.3%, p = 0.23
  • Stent thrombosis: 0% vs. 0.6%, p = 0.15
  • Stroke or systemic embolism: 5.5% vs. 3.8%, p = 0.29
  • ISTH major bleeding: 10.4% vs. 7.8%, p = 0.22
  • TIMI major bleeding: 8.4% vs. 4.9%, p = 0.07
  • Warfarin: 75%, aspirin: 86%, clopidogrel: 15%, statins: 79%

Interpretation:

Due to premature cessation of the trial, noninferiority of OAC alone could not be established compared with OAC + SAPT among patients with AF and stable CAD with remote PCI. MI rates were extremely low overall (1-2% over 2.5 years). Not surprisingly, bleeding tended to be lower in the OAC alone arm.

This is a common problem among patients with AF. Trials such as WOEST, PIONEER AF-PCI, and RE-DUAL PCI have demonstrated the safety of dual therapy over triple therapy for patients needing both DAPT post-PCI and OAC. This trial addresses a more downstream question – PCI was performed >1 year ago, when guidelines recommend switching to SAPT over DAPT unless thrombotic risk is high. Both the European Society of Cardiology guidelines and the North American expert consensus document recommend lifelong OAC alone without APT in patients with low thrombotic risk, particularly if also high bleeding risk, beyond 1 year after PCI. Thus, although this is a very important topic to study, this trial was unfortunately terminated early due to slow enrollment, partly because enrolling physicians did not feel comfortable stopping APT in stented patients. Only 25% of patients in this trial were on a DOAC – unclear if this would have been a better group to study.

References:

Matsumura-Nakano Y, Shizuta S, Komasa A, et al., on behalf of the OAC-ALONE Study Investigators. An Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond One Year After Coronary Stent Implantation: The OAC-ALONE Study. Circulation 2018;Sep 24:[Epub ahead of print].

Editorial Comment: Lemesle G. Aspirin on Top of Anticoagulation in Patients With Concomitant Stable Coronary Artery Disease and Atrial Fibrillation: No Clear Answer Yet. Circulation 2018;Sep 24:[Epub ahead of print].

Presented by Dr. Yukiko Matsumura-Nakano at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2018), San Diego, CA, September 24, 2018.

Keywords: TCT18, Transcatheter Cardiovascular Therapeutics, Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Coronary Artery Disease, Drug-Eluting Stents, Embolism, Geriatrics, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Stents, Stroke, Thrombosis, Vascular Diseases, Warfarin


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