Antiplatelet Removal and Hemocompatibility Events With the HeartMate 3 Pump - ARIES-HM3

Nov 11, 2023
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Anthony A. Bavry, MD,MPH,FACC
Trial Sponsor:
Abbott Inc.
Date Presented:
11/11/2023
Date Published:
11/11/2023
Date Updated:
11/11/2023
Original Posted Date:
11/10/2023
References

Contribution To Literature:

The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 LVAD and were anticoagulated with a VKA, placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year.

Description:

The goal of the trial was to determine whether antithrombotic therapy with a vitamin K antagonist (VKA) alone was noninferior to combination treatment with VKA and aspirin in patients who underwent implantation with a HeartMate 3 (HM3) left ventricular assist device (LVAD) for advanced heart failure (HF).

Study Design

  • International
  • Randomized
  • Double-blind
  • Placebo-controlled

Patients with advanced HF with reduced ejection fraction (HFrEF) who underwent HM3 implantation were randomized to receive aspirin 100 mg daily (n = 314) or matching placebo (n = 314) in addition to a VKA (international normalized ratio [INR] goal 2.0-3.0).

  • Total number of enrollees: 628
  • Duration of follow-up: 24 months
  • Median patient age: 60 years
  • Percentage female: 23%

Inclusion criteria:

  • Age ≥18 years
  • First durable LVAD implantation with HM3 for an approved indication per local guidelines

Exclusion criteria:

  • Additional temporary or permanent mechanical circulatory support (MCS) in addition to HM3
  • Alternative indication or contraindication for antiplatelet therapy
  • Inability to take oral medications through day 7 postoperatively
  • Aspirin allergy

Other salient features/characteristics:

  • History of prior stroke: 13%
  • History of prior major bleeding: 5%
  • Implantation at US-based center: 85%
  • Median time in therapeutic INR range, placebo vs. aspirin: 55.1% vs. 58.9% (p = 0.93)

Principal Findings:

The primary outcome, survival free from nonsurgical hemocompatibility-related adverse event (i.e., stroke, pump thrombosis, major bleeding, or arterial thromboembolism >14 days post-implant), for placebo vs. aspirin at 1 year, was: 74.2 vs. 68.1 events per 100 patient-years (p for noninferiority < 0.0001).

Secondary outcomes for placebo vs. aspirin at 1 year, events per 100 patient-years:

  • Nonsurgical bleeding: 25.9 vs. 39.5 (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.51-0.85, p < 0.01)
  • Gastrointestinal bleeding: 13.1 vs. 21.6 (HR 0.61, 95% CI 0.42-0.87, p < 0.01)
  • Stroke: 1.9 vs. 3.7 (HR 0.52, 95% CI 0.21-1.30, p = 0.16)

Primary composite outcome among subgroups of interest, placebo vs. aspirin:

  • Prior stroke: 80.5 vs. 54.8 events per 100 patient-years (relative risk [RR] 25.6, 95% confidence interval [CI] 4.3-47.0, p for interaction = 0.055)
  • Prior bleeding: 71.0 vs. 30.4 events per 100 patient-years (RR 40.5, 95% CI 13.8-67.2, p for interaction = 0.008)

Interpretation:

The ARIES-HM3 trial demonstrated that a management strategy excluding aspirin in patients with an HM3 device was noninferior to combination therapy with a VKA and aspirin with respect to bleeding and thrombotic complications up to 1-year post-implantation. Although the study was not designed to test for superiority, survival free from bleeding, stroke, and the composite hemocompatibility endpoint seemed to favor the placebo arm. The authors also observed 47% and 41% decreases in cumulative hospitalization days and hospitalization costs, respectively, due to major bleeding events.

Antithrombotic therapy following LVAD implantation has conventionally included treatment with both a VKA and aspirin. The HM3 device is a fully magnetically levitated pump that has previously demonstrated improved hemocompatibility compared with the preceding HeartMate II. Moreover, prior small observational studies examining aspirin withdrawal in HM3 patients at increased bleeding risk have suggested outcomes comparable to controls at up to 2 years. ARIES-HM3 provides the first randomized data that may support an aspirin-sparing regimen in HM3 patients, particularly those at increased risk of major bleeding.

References:

Mehra MR, Netuka I, Uriel N, et al., on behalf of the ARIES-HM3 Investigators. Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial. JAMA 2023;Nov 11:[Epub ahead of print].

Presented by Dr. Mandeep Mehra at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Advanced Heart Failure, AHA23, Anticoagulation Therapy


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