Abstract
Background
Lipoprotein(a) is simply a presumed hazard origin for atherosclerotic cardiovascular disease. Olpasiran is simply a tiny interfering RNA that reduces lipoprotein(a) synthesis successful the liver.
Methods
We conducted a randomized, double-blind, placebo-controlled, dose-finding proceedings involving patients with established atherosclerotic cardiovascular illness and a lipoprotein(a) attraction of much than 150 nmol per liter. Patients were randomly assigned to person 1 of 4 doses of olpasiran (10 mg each 12 weeks, 75 mg each 12 weeks, 225 mg each 12 weeks, oregon 225 mg each 24 weeks) oregon matching placebo, administered subcutaneously. The superior extremity constituent was the percent alteration successful the lipoprotein(a) attraction from baseline to week 36 (reported arsenic the placebo-adjusted mean percent change). Safety was besides assessed.
Results
Among the 281 enrolled patients, the median attraction of lipoprotein(a) astatine baseline was 260.3 nmol per liter, and the median attraction of low-density lipoprotein cholesterin was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin–kexin benignant 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) attraction had accrued by a mean of 3.6% successful the placebo group, whereas olpasiran therapy had importantly and substantially reduced the lipoprotein(a) attraction successful a dose-dependent manner, resulting successful placebo-adjusted mean percent changes of −70.5% with the 10-mg dose, −97.4% with the 75-mg dose, −101.1% with the 225-mg dose administered each 12 weeks, and −100.5% with the 225-mg dose administered each 24 weeks (P<0.001 for each comparisons with baseline). The wide incidence of adverse events was akin crossed the proceedings groups. The astir communal olpasiran-related adverse events were injection-site reactions, chiefly pain.
Conclusions
Olpasiran therapy importantly reduced lipoprotein(a) concentrations successful patients with established atherosclerotic cardiovascular disease. Longer and larger trials volition beryllium indispensable to find the effect of olpasiran therapy connected cardiovascular disease. (Funded by Amgen; OCEAN[a]-DOSE ClinicalTrials.gov number, NCT04270760.)
Continue speechmaking this article
Select an enactment below:
This contented requires an account.
Create AccountAlready person an account?
Sign InFunding and Disclosures
Supported by Amgen.
Disclosure forms provided by the authors are disposable with the afloat substance of this nonfiction astatine NEJM.org.
This nonfiction was published connected November 6, 2022, astatine NEJM.org.
A data sharing statement provided by the authors is disposable with the afloat substance of this nonfiction astatine NEJM.org.
We convey the patients who participated successful this trial.
Author Affiliations
From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston (M.L.O., J.F.K., X.R., S.A.M., M.S.S.); the Icahn School of Medicine, Mount Sinai Hospital, New York (R.S.R.); the Division of Cardiology, Geneva University Hospitals, Geneva, and the Institute of Primary Health Care, University of Bern, Bern — some successful Switzerland (B.G.); Global Development, Amgen, Thousand Oaks (J.A.G.L., B.K., H.W., Y.W., H.K.), and the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (N.E.L.) — some successful California; Flourish Research and the Charles E. Schmidt College of Medicine, Florida Atlantic University — some successful Boca Raton (S.J.B.); Crossroads Clinical Research, Mooresville, NC (E.S.); and the Department of Medicine, Université de Montréal, Montreal, and ECOGENE-21, Chicoutimi, QC — some successful Canada (D.G.).
Dr. O’Donoghue tin beryllium contacted astatine [email protected] oregon astatine the TIMI Study Group, Brigham and Women’s Hospital, 60 Fenwood Rd., 7th Fl., Boston, MA 02115.
A database of the OCEAN(a)-DOSE proceedings investigators is provided successful the Supplementary Appendix, disposable astatine NEJM.org.
English (US)