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On-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways is not affected by pelacarsen

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Abstract

Background

Pelacarsen decreases plasma levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPL). It was previously reported that pelacarsen does not affect the platelet count. We now report the effect of pelacarsen on on-treatment platelet reactivity.

Methods

Subjects with established cardiovascular disease and screening Lp(a) levels ≥60 mg per deciliter (~ ≥150 nmol/L) were randomized to receive pelacarsen (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or placebo for 6–12 months. Aspirin Reaction Units (ARU) and P2Y12 Reaction Units (PRU) were measured at baseline and the primary analysis timepoint (PAT) at 6 months.

Results

Of the 286 subjects randomized, 275 had either an ARU or PRU test, 159 (57.8%) were on aspirin alone and 94 (34.2%) subjects were on dual anti-platelet therapy. As expected, the baseline ARU and PRU were suppressed in subjects on aspirin or on dual anti-platelet therapy, respectively. There were no significant differences in baseline ARU in the aspirin groups or in PRU in the dual anti-platelet groups. At the PAT there were no statistically significant differences in ARU in subjects on aspirin or PRU in subjects on dual anti-platelet therapy among any of the pelacarsen groups compared to the pooled placebo group (p > 0.05 for all comparisons).

Conclusion

Pelacarsen does not modify on-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways.

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Authors and Affiliations

  1. Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA

    Ewa Karwatowska-Prokopczuk, Lu Li, Jun Yang, Joseph L. Witztum & Sotirios Tsimikas

  2. Vascular Medicine Program, Sulpizio Cardiovascular Center, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, CA, 92093-0682, USA

    Sotirios Tsimikas

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  1. Ewa Karwatowska-Prokopczuk
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  2. Lu Li
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  3. Jun Yang
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  4. Joseph L. Witztum
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  5. Sotirios Tsimikas
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Correspondence to Sotirios Tsimikas.

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Disclosures

EKP, SX, and LL are employees of Ionis Pharmaceuticals and ST is an employee of Ionis Pharmaceuticals and UCSD. JLW is a consultant to Ionis Pharmaceuticals. JLW and ST are co-inventors and receive royalties from patents owned by UCSD on oxidation-specific antibodies and of biomarkers related to oxidized lipoproteins and are co-founders and have an equity interest in Oxitope, Inc and Kleanthi Diagnostics, LLC (“Kleanthi”). JY has no relevant conflicts.

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Karwatowska-Prokopczuk, E., Li, L., Yang, J. et al. On-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways is not affected by pelacarsen. J Thromb Thrombolysis 56, 226–232 (2023). https://doi.org/10.1007/s11239-023-02818-6

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