Impact of evolocumab on coronary physiology and microstructure in de-novo heart transplant recipients

Cardiac allograft vasculopathy, characterized by arterial intima thickening and microvascular dysfunction, compromises survival after heart transplantation. We investigated the impact of evolocumab on invasive coronary physiology and microstructure after de-novo transplantation.

In the EVOLVD trial (NCT03734211), the effect of 12 months of evolocumab vs placebo on maximal coronary intimal thickness was assessed using intracoronary ultrasound. For this substudy, optical coherence tomography (OCT), fractional flow reserve (FFR), coronary flow reserve (CFR), microvascular resistance reserve (MRR), and index of microcirculatory resistance (IMR) were performed at baseline (4-8 weeks post-transplant) and at 12 months post-transplant.

Seventy-five de-novo heart transplant recipients were included, randomized to placebo (n = 36) or evolocumab (n = 39). Over 12 months, no between-group differences were observed in changes in coronary physiology (FFR: Δ 0.001 [IQR -0.03 to 0.02], p = 0.42; CFR: Δ 0.59 [IQR -1.33 to 1.90], p = 0.69; IMR: Δ 0.76 [IQR -6.86 to 8.32], p = 0.09; MRR: Δ 0.19 [IQR -1.85 to 2.60], p = 0.70) or coronary microstructure (lumen area: Δ -1.37 mm² [IQR -3.53 to 0.09], p = 0.38; intima area: Δ 0.05 mm² [IQR 0.02 to 0.17], p = 0.88. Among all patients, OCT showed a lumen area decrease of -1.37 [IQR -3.53 to -0.69] mm² (p < 0.01) and intima area increasse of 0.04 [IQR 0.01 to 0.17] mm² (p < 0.01) from baseline to follow-up.

Evolocumab did not affect coronary physiology or OCT measurements 12 months after de-novo heart transplantation. OCT revealed progressive intimal proliferation and luminal narrowing in both groups, while coronary physiology remained unchanged and did not differ between treatment arms.