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Efficacy and safety of more potent antiplatelet therapy with vorapaxar in patients with impaired renal function

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Abstract

Patients with renal disease are often undertreated with antiplatelet therapy due to concerns about bleeding. Vorapaxar blocks platelet activation via the PAR-1 receptor and reduces cardiovascular events in patients with stable atherosclerosis, but with increased bleeding. We examined the efficacy and safety of vorapaxar in patients with impaired renal function. TRA2°P-TIMI 50 randomized patients with stable atherosclerosis to vorapaxar or. We analyzed patients with eGFR assessed who qualified with a history of MI or PAD (without stroke or TIA) (n = 19,932). Cox models assessed the risk of CV events and bleeding by quartile of baseline eGFR in the placebo arm and then by randomized assignment. Net clinical outcome (NCO) was predefined as CV death, MI, stroke, or GUSTO severe bleeding. Patients with lower eGFR tended to be older, female, have hypertension, hyperlipidemia or prior PAD. In the placebo arm, baseline eGFR in the lowest quartile was associated with a 26% higher risk of CV death, MI or stroke (Q1:Q4 HRadj 1.26, 1.03–1.55) and 73% higher risk of GUSTO moderate or severe bleeding (HRadj 1.73, 1.12–2.65). Vorapaxar reduced the risk of MACE to a similar extent (14–26%) across quartiles of baseline eGFR (P interaction = 0.70) and increased the relative risk of GUSTO moderate or severe bleeding (P interaction = 0.54). NCO was similar across quartiles of eGFR (P interaction = 0.65). Intensification of antiplatelet therapy with vorapaxar offers comparable net clinical benefit regardless of baseline renal function. These data support the use of more potent antiplatelet regimens in patients with renal dysfunction.

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Authors and Affiliations

  1. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, 60 Fenwood Rd., Suite 7022, Boston, MA, 02115, USA

    Simon Correa, Marc P. Bonaca, Benjamin M. Scirica, Sabina A. Murphy, Erica L. Goodrich, David A. Morrow & Michelle L. O’Donoghue

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  1. Simon Correa
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  2. Marc P. Bonaca
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Correspondence to Simon Correa.

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Conflict of interest

Dr. Bonaca reports grant support from Amgen, AstraZeneca, Merck, MedImmune and Pfizer; and receipt of consulting fees from Amgen, Aralez, AstraZeneca, Bayer, Janssen, Merck and Sanofi. Dr. Scirica reports research grants via Brigham and Women’s Hospital from AstraZeneca, Eisai, Novartis, and Merck; consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr. Reddy’s Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Merck, NovoNordisk, Sanofi, St. Jude’s Medical; and equity in Health [at] Scale. Dr. Morrow reports receipt of consulting fees from Abbott Laboratories, Aralez, AstraZeneca, DiaDexus, GlaxoSmithKline, Merck and Company, Peloton, Roche Diagnostics, Verseon; and research grants from Abbott, Amgen, AstraZeneca, Daichii Sankyo Ltd, GlaxoSmithKline, Merck and Company, Pfizer, Novartis Pharmaceuticals, Roche Diagnostics. Dr. O’Donoghue reports research grants from GlaxoSmithKline, Eisai, AstraZeneca, Merck, Janssen, The Medicines Company. Dr Simon Correa, Erica Goodrich and Sabina Murphy have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Research involving human participants and/or animals and Informed consent

In the TRA2°P-TIMI 50 trial, informed consent was obtained from all individual participants included in the study.

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Correa, S., Bonaca, M.P., Scirica, B.M. et al. Efficacy and safety of more potent antiplatelet therapy with vorapaxar in patients with impaired renal function. J Thromb Thrombolysis 47, 353–360 (2019). https://doi.org/10.1007/s11239-018-1779-y

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