Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-Novo Heart Transplant Recipients - EVOLVD

Jul 15, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Amgen
Date Published:
06/26/2024
Date Updated:
07/15/2024
Original Posted Date:
07/15/2024
References

Contribution To Literature:

The EVOLVD trial showed that, compared with placebo, administration of evolocumab 420 mg monthly resulted in a greater reduction in LDL-C but no change in maximal intimal thickness on IVUS among recent recipients of a cardiac allograft.

Description:

The goal of the trial was to demonstrate the efficacy of evolocumab on coronary intimal thickness in heart transplant recipients.

Study Design

Eligible patients were randomized in a 1:1 fashion to receive either 420 mg evolocumab (n = 56) or placebo (n = 54), administered monthly via subcutaneous injection for 12 months. Intravascular ultrasound (IVUS) was performed at baseline, 4-8 weeks after transplantation, and after 12 months of treatment, in conjunction with coronary angiography.

  • Total number of enrollees: 110
  • Duration of follow-up: 1 year
  • Mean patient age: 53 years
  • Percentage female: 26%
  • White race: 97%

Inclusion criteria:

  • Age ≥18 years
  • Received a cardiac allograft at one of the Nordic transplant centers within the prior 4-8 weeks

Exclusion criteria:

  • Estimated glomerular filtration rate <20 mL/min/1.73 m2
  • On renal replacement therapy
  • Intolerance to evolocumab
  • Treatment with a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor
  • Contraindications to coronary angiography with IVUS

Other salient features/characteristics:

  • Diabetes: 19%
  • Previous stroke or transient ischemic attack: 9%
  • Statin use: 98% (75% on pravastatin)
  • Immunosuppression: Tacrolimus: 89%, cyclosporine: 10%, everolimus: 21%, myophenolate: 95%, prednisolone: 98%
  • Angiotensin-converting enzyme inhibitor: 16%
  • Baseline low-density lipoprotein cholesterol (LDL-C): 99 mg/dL

Principal Findings:

The primary endpoint, change from baseline in maximal intimal thickness, for evolocumab vs. placebo, was: +0.036 vs. +0.046 mm; between-group difference in the baseline-adjusted coronary intimal thickness = -0.017 mm (p = 0.14).

Secondary outcomes for evolocumab vs. placebo:

  • Change in percent atheroma volume: 1.3% vs. 1.8%, baseline-adjusted between-group difference: -0.44% (p > 0.05)
  • Deaths: 3 vs. 1

Interpretation:

The results of this trial indicate that compared with placebo, administration of evolocumab 420 mg monthly resulted in a greater reduction in LDL-C but no change in maximal intimal thickness on IVUS among recent recipients of a cardiac allograft. Most patients were also on a statin, primarily pravastatin. A large number of patients were also on an mTOR inhibitor.

Cardiac allograft vasculopathy differs from ordinary atherosclerotic disease. It often manifests as a panarterial rather than patchy disease, and is associated with alloantibodies with a significant immunological component. Statins have been shown to lower the risk of cardiac allograft vasculopathy. The current trial suggests that evolocumab does not lower this risk, with the caveat that this was a small study with only 12 months of follow-up.

References:

Broch K, Lemström KB, Gustafsson F, et al. Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients. JACC Heart Fail 2024;Jun 26:[Epublished].

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Lipid Metabolism, Nonstatins, Heart Transplant, Prevention

Keywords: Cholesterol, LDL, Heart Transplantation


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