{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:59:58Z","timestamp":1790740798037,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,8,27]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular disease. Currently, there are few available therapies to lower Lp(a). We sought to evaluate the impact of AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), on Lp(a).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              As part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)\u2013Thrombolysis in Myocardial Infarction (TIMI) 57 trial, 631 patients with hypercholesterolemia receiving statin therapy were randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters were measured at baseline and at week 12. Compared with placebo, AMG145\u200970 mg, 105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%, respectively (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 for each dose versus placebo). Likewise, AMG145\u2009280 mg, 350 mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 for each dose versus placebo). The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol (\u03c1=0.33,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen. Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with AMG145 compared with those with lower baseline Lp(a) values.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>AMG145 significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolemia receiving statin therapy, offering an additional, complementary benefit beyond robust low-density lipoprotein cholesterol reduction with regard to a patient\u2019s atherogenic lipid profile.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT01380730.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.113.001969","type":"journal-article","created":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T01:23:25Z","timestamp":1374715405000},"page":"962-969","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":158,"title":["AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy"],"prefix":"10.1161","volume":"128","author":[{"given":"Nihar R.","family":"Desai","sequence":"first","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Kohli","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ransi","family":"Somaratne","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine B.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fannie","family":"Huang","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Rogers","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Scott","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. Scott); and University of Alabama at Birmingham (W.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (N.R.D., P.K., R.P.G., M.L.O\u2019D., J.Z., E.B.H., M.S.S.); Amgen, Inc, Thousand Oaks, CA (R. Somaratne, F.H., S.M.W., R. 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