PCSK9 Inhibitors Found Safe, Effective in Solid Organ Transplant Recipients

A recent network meta-analysis (NMA) found that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were generally effective and well-tolerated in patients who have underwent a solid organ transplant (SOT), according to results published in Frontiers in Pharmacology Drug Outcomes Research and Policies.¹

The analysis showed that evolocumab (Repatha; Amgen) was optimal for low-density lipoprotein cholesterol (LDL-C) and cardiovascular event (CVE) reduction and ongericimab (Junshi Biosciences) and alirocumab (Praluent; Regeneron, Sanofi) offered more tolerable safety profiles for patients.¹

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PCSK9 Inhibitors: Generally Effective, Though Questions Remain for Transplant Recipients

PCSK9 inhibitors are novel treatment options for patients to manage their cholesterol. By inhibiting PCSK9, these medications allow for more LDL receptors in the liver to work properly, more effectively breaking down and removing LDL-C from the body. These medications provide patients struggling to lower their LDL-C with a new option that can be more easily adhered to than standard lipid-lowering therapies (LLTs). Evolocumab and alirocumab, along with the more recent ongericimab, are some of a series of monoclonal antibody forms of PCSK9 inhibitors that have been manufactured and widely used.^1,2

As the use of PCSK9 inhibitors broadens, concerns abound regarding the impacts these medications may have on population subgroups, including individuals who are recipients of a SOT. Research shows that, due to the long-term use of immunosuppresants to facilitate the transplant process, SOT recipients face a heightened risk of dyslipidemia, increased susceptibility to infections, tumor recurrence, and the development of novel malignancies.^1,3

It is critical to better elucidate the value of PCSK9 inhibitors in both the general population and SOT recipients. Accordingly, the current authors conducted a meta-analysis of randomized controlled trials to assess the differences in LDL-C reduction between PCSK9 inhibitors and other LLTs, in addition to a safety evaluation, with a particular focus on potential adverse reactions in either patient group. A total of 16 articles were ultimately included in the analysis following an identification and exclusion effort.¹

Network Meta-Analysis Reveals Evolocumab’s Effectiveness, Alirocumab’s Safety in SOT Recipients

For 9 studies, the impact of different treatment regimens (DTRs) on LDL-C were investigated, with 40,378 individuals analyzed across 5 intervention groups: evolocumab, alirocumab, inclisiran (Leqvio; Novartis), tafolecimab (Sintbilo; Innovent Biologics Co), and placebo. Evolocumab was found to have the highest likelihood of LDL-C reduction (67.2%), followed by alirocumab (66.6%) and tafolecimab (65.7%). For CVE reduction, which included 6 studies and 75,056 patients across 3 intervention groups, evolocumab (69.5%) had a significantly higher reduction in LDL-C levels compared with placebo (61.6%) and alirocumab (18.9%).¹

Specifically, evolocumab meaningfully reduced the risk of myocardial infarction (28%), stroke (19%), and coronary revascularization (32%). On the other hand, alirocumab demonstrated a significant protective effect on coronary revascularization (21%), but the authors observed a weaker impact on myocardial infarction and stroke, highlighting evolocumab’s superiority.¹

Regarding safety—which was investigated in 11 studies and 51,321 patients—ongericimab (91.3%), followed by tafolecimab (82.8%), alirocumab (59.0%), placebo (48.6%), and evolocumab (47.4%) reduced the incidence of total adverse events from highest to lowest. The effect of PCSK9’s on neurocognitive events was also investigated, with the cohort including 49,453 patients across 3 intervention groups. From highest to lowest reductions, alirocumab (89.5%), placebo (44.3%), and evolocumab reduced the incidence of neurocognitive events.¹

The authors also evaluated transplant-related outcomes. Importantly, a subgroup analysis indicated that PCSK9 inhibitors did not meaningfully increase the risk of acute rejection in transplant recipients (odds ratio [OR]: 1.05 [95% CI, 0.82–1.34]), though the investigators noted that the sample size was small (n = 127). In addition, there were no major differences in infection risk between the intervention and transplant groups (OR: 0.93 [95% CI, 0.75–1.16]). Interestingly, there was a significantly larger reduction in LDL-C in heart transplant recipients treated with evolocumab compared with liver transplant recipients, though there were no concurrent increases in infection risk.¹

This meta-analysis affirms the broad safety and effectiveness of PCSK9 inhibitors at reducing LDL-C and CVEs in both the general population and in patients with SOT. Given their unique immunocompromised status—which is likely chronic and requires consistent, stringent management—patients who have received SOT are at especially heightened risk of dyslipidemia.

Pharmacists play a significant role in counseling SOT recipients as to their increased risk of high cholesterol and in guiding them towards appropriate options to reduce their risk.¹

“PCSK9 inhibitors effectively reduced LDL-C in transplant recipients without increasing acute rejection or infection risks, supporting their use in this population,” the investigators concluded. “In clinical practice, PCSK9 inhibitor selection should be individualized, balancing evolocumab’s efficacy advantages with the safety benefits of ongericimab/alirocumab, while considering patient-specific risks and transplant status.”¹

REFERENCES

1. Luo B, Sun Z, Luo H. Efficacy and safety of different proprotein convertase subtilisin/kexin type 9 inhibitors in the general population and solid organ transplant recipients: a network meta-analysis. Front Pharmacol. 2025;16. doi:10.3389/fphar.2025.1584612

2. Halpern L. Novel PCSK9 Inhibitor Recaticimab Lowers LDL-C in Adult Heterozygous Familial Hypercholesterolemia. Pharmacy Times. Published September 12, 2025. Accessed September 15, 2025. https://www.pharmacytimes.com/view/novel-pcsk9-inhibitor-recaticimab-lowers-ldl-c-in-adult-heterozygous-familial-hypercholesterolemia

3. Jennings DL, Sultan L, Mingov J, et al. PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis. Heart Fail Rev. 2023;28(1):149-156. doi:10.1007/s10741-022-10255-5