Lipoprotein(a) Reduction in Persons with Cardiovascular Disease
Elevated levels of lipoprotein(a) in the plasma are a risk factor for cardiovascular disease, and lowering levels can be achieved with antisense oligonucleotide targeting LPA messenger RNA, which encodes lipoprotein(a). This trial tested whether the same effect can be achieved in persons with establ...
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| Published in | The New England journal of medicine Vol. 382; no. 3; pp. 244 - 255 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Massachusetts Medical Society
16.01.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0028-4793 1533-4406 1533-4406 |
| DOI | 10.1056/NEJMoa1905239 |
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| Abstract | Elevated levels of lipoprotein(a) in the plasma are a risk factor for cardiovascular disease, and lowering levels can be achieved with antisense oligonucleotide targeting
LPA
messenger RNA, which encodes lipoprotein(a). This trial tested whether the same effect can be achieved in persons with established cardiovascular disease. |
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| AbstractList | Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.BACKGROUNDLipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).METHODSWe conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.RESULTSThe median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).CONCLUSIONSAPO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.). Elevated levels of lipoprotein(a) in the plasma are a risk factor for cardiovascular disease, and lowering levels can be achieved with antisense oligonucleotide targeting LPA messenger RNA, which encodes lipoprotein(a). This trial tested whether the same effect can be achieved in persons with established cardiovascular disease. BackgroundLipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.MethodsWe conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses).ResultsThe median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions.ConclusionsAPO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.) Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-L , referred to here as APO(a)-L (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-L resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-L dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions. APO(a)-L reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.). |
| Author | Steinhagen-Thiessen, Elizabeth Tardif, Jean-Claude Shapiro, Michael D Viney, Nicholas J Baum, Seth J Tsimikas, Sotirios O’Dea, Louis Xia, Shuting Moriarty, Patrick M Witztum, Joseph L Stroes, Erik S Nordestgaard, Børge G Guerriero, Jonathan Gouni-Berthold, Ioanna Karwatowska-Prokopczuk, Ewa |
| Author_xml | – sequence: 1 givenname: Sotirios surname: Tsimikas fullname: Tsimikas, Sotirios organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 2 givenname: Ewa surname: Karwatowska-Prokopczuk fullname: Karwatowska-Prokopczuk, Ewa organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 3 givenname: Ioanna surname: Gouni-Berthold fullname: Gouni-Berthold, Ioanna organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 4 givenname: Jean-Claude surname: Tardif fullname: Tardif, Jean-Claude organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 5 givenname: Seth J surname: Baum fullname: Baum, Seth J organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 6 givenname: Elizabeth surname: Steinhagen-Thiessen fullname: Steinhagen-Thiessen, Elizabeth organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 7 givenname: Michael D surname: Shapiro fullname: Shapiro, Michael D organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 8 givenname: Erik S surname: Stroes fullname: Stroes, Erik S organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 9 givenname: Patrick M surname: Moriarty fullname: Moriarty, Patrick M organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 10 givenname: Børge G surname: Nordestgaard fullname: Nordestgaard, Børge G organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 11 givenname: Shuting surname: Xia fullname: Xia, Shuting organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 12 givenname: Jonathan surname: Guerriero fullname: Guerriero, Jonathan organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 13 givenname: Nicholas J surname: Viney fullname: Viney, Nicholas J organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 14 givenname: Louis surname: O’Dea fullname: O’Dea, Louis organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark – sequence: 15 givenname: Joseph L surname: Witztum fullname: Witztum, Joseph L organization: From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL (S.J.B.); the Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, Berlin Institute of Health, Berlin (E.S.-T.), and the Division of Geriatrics, University Medicine Greifswald, Greifswald (E.S.-T.) — both in Germany; the Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland (M.D.S.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S.); the Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City (P.M.M.); and the Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev (B.G.N.), and the Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (B.G.N.) — all in Denmark |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31893580$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Contributor | Nordestgaard, Bǿrge Shapiro, Michael Strader, Russell Ballantyne, Christie Tardif, Jean-Claude Khandelwal, Abha Moriarty, Patrick Thanassoulis, George Ahmed, Haitham Gaudet, Daniel Klausen, Ib Christian Butman, Samuel Stroes, Erik Rosenson, Robert Baum, Seth Bergeron, Jean Miller, Michael McPherson, Ruth Steinhagen-Thiessen, Elizabeth DeFranco, Anthony Shah, Prediman Krishan Aspry, Karen Myerson, Merle Maron, David Andersen, Rolf Hemphill, Linda Weintraub, Howard Gouni-Berthold, Ioanna Koren, Michael Cuchel, Marina DeMaria, Anthony |
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| Copyright | Copyright © 2020 Massachusetts Medical Society. All rights reserved. Copyright © 2020 Massachusetts Medical Society. |
| Copyright_xml | – notice: Copyright © 2020 Massachusetts Medical Society. All rights reserved. – notice: Copyright © 2020 Massachusetts Medical Society. |
| CorporateAuthor | AKCEA-APO(a)-LRx Study Investigators |
| CorporateAuthor_xml | – name: AKCEA-APO(a)-LRx Study Investigators |
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| DOI | 10.1056/NEJMoa1905239 |
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| Snippet | Elevated levels of lipoprotein(a) in the plasma are a risk factor for cardiovascular disease, and lowering levels can be achieved with antisense... Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved... BackgroundLipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no... |
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| SubjectTerms | Adult Aged Antisense oligonucleotides Aortic stenosis Apolipoproteins Blood platelets Blood pressure Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - blood Cardiovascular Diseases - drug therapy Cholesterol - blood Dose-Response Relationship, Drug Double-Blind Method Drug dosages Female Health risk assessment Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Hypolipidemic Agents - administration & dosage Hypolipidemic Agents - adverse effects Hypolipidemic Agents - therapeutic use Influenza Laboratories Least-Squares Analysis Lipoprotein(a) - blood Low density lipoprotein Male Middle Aged Oligonucleotides - administration & dosage Oligonucleotides - adverse effects Patients Risk Factors Stenosis Urine |
| Title | Lipoprotein(a) Reduction in Persons with Cardiovascular Disease |
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