PCSK9 Inhibitors Safely and Effectively Lower LDL After Heart Transplantation: A Systematic Review and Meta-Analysis

Abstract

<h3>Purpose</h3> Coronary allograft vasculopathy (CAV) continues to afflict a majority of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT, however data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. <h3>Methods</h3> We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15^th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. <h3>Results</h3> `A total of six studies including 97 patients were evaluated, most of which either had statin intolerance or refractory hyperlipidemia. Over a mean follow up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI -119.15 to -46.07; <i>I²</i>=82%) (<b>Figure 1</b>) from baseline. Serious adverse drug reactions were rarely reported, and none were attributable to the PCSK9i therapy. Three studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. No studies reported on immunologic safety (i.e. development of DSA), hence this endpoint cannot be assessed. <h3>Conclusion</h3> Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.