Trial reportCirculation. Genomic and precision medicine2018
Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study.
Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph
Trial report in Circulation. Genomic and precision medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00461630. Cited by 37 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
9.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Trial of the Long-term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant
Open the trial in the graphWho cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk.International journal of molecular sciences · 2022Pooled it
- Existing and Potential Therapeutic Strategies for Lowering Lipoprotein(a) Levels: An Update.Journal of clinical medicine · 2026Review
- Lipoprotein(a): structural basis, bidirectional risk, and therapeutic frontiers.Journal of clinical biochemistry and nutrition · 2026Article
- Lipoprotein(a) in Vietnamese Cardiologists: Findings From a Pilot Study at the Vietnam Atherosclerosis Society Congress.Health science reports · 2025Article
- Interaction Between Lipoprotein(a) and Other Lipid Molecules: A Review of the Current Literature.Biomolecules · 2025Review
- Lipoprotein(a) as a Causal Risk Factor for Cardiovascular Disease.Current cardiovascular risk reports · 2025Review
- Role of Lipoprotein(a) Reduction in Cardiovascular Disease.Journal of clinical medicine · 2024Review
- Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024Review
- Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk.Journal of the American Heart Association · 2024Review
- Novel Therapeutic Approaches for the Management of Elevated Lipoprotein(a): From Traditional Agents to Future Treatment Options.Life (Basel, Switzerland) · 2024Review
- Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.Archives of medical science : AMS · 2024Article
- Lipoprotein(a)-60 Years Later-What Do We Know?Cells · 2023Review
- Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods.International journal of molecular sciences · 2023Review
- Novel Pharmacological Therapies for the Management of Hyperlipoproteinemia(a).International journal of molecular sciences · 2023Review
- Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels-Potent Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment.Molecules (Basel, Switzerland) · 2023Review
- Associations of lipid measures with total occlusion in patients with established coronary artery disease: a cross-sectional study.Lipids in health and disease · 2022Article
- Article
- Approach to risk stratification of atherosclerotic cardiovascular disease: Use of biomarkers and imaging in a Canadian context.Canadian family physician Medecin de famille canadien · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Sarah ParishFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13. sarah.parish@ndph.ox.ac.uk.
Jemma C HopewellFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Michael R HillFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Santica MarcovinaFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Elsa Valdes-MarquezFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Richard HaynesFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Alison OfferFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Terje R PedersenFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Colin BaigentFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Rory CollinsFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Martin LandrayFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
Jane ArmitageFrom the Medical Research Council Population Health Research Unit (S.P., M.R.H., R.H., C.B., J.A.); and the Clinical Trial Service Unit and Epidemiological Studies Unit (S.P., J.C.H., M.R.H., E.V.-M., R.H., A.O., C.B., R.C., M.L., J.A.), Nuffield Department of Population Health, University of Oxford, United Kingdom; Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.); and Center for Preventive Medicine, University of Oslo, Norway (T.R.P.). A complete list of collaborators in HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is given in reference 13.
HPS2-THRIVE Collaborative Group
University of Washington · USMedical Research Council · GB
Funding
British Heart Foundation CH/1996001/9454British Heart Foundation FS/14/55/30806British Heart Foundation SP/14/3/31114Cancer Research UKMedical Research Council MC_U137686853Medical Research Council MC_U137686855Medical Research Council MC_UU_12026/5
Abstract
backgroundGenetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear.
methodsHPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin-laropiprant versus placebo on a background of simvastatin therapy. Plasma Lp(a) levels at baseline and 1 year post-randomization were measured in 3978 participants from the United Kingdom and China. Apolipoprotein(a) isoform size, estimated by the number of kringle IV domains, was measured by agarose gel electrophoresis and the predominantly expressed isoform identified.
resultsAllocation to niacin-laropiprant reduced mean Lp(a) by 12 (SE, 1) nmol/L overall and 34 (6) nmol/L in the top quintile by baseline Lp(a) level (Lp[a] ≥128 nmol/L). The mean proportional reduction in Lp(a) with niacin-laropiprant was 31% but varied strongly with predominant apolipoprotein(a) isoform size (
conclusionsProportional reductions in Lp(a) were dependent on apolipoprotein(a) isoform size. Taking this into account, the likely benefits of niacin-laropiprant on coronary risk through Lp(a) lowering are small. Novel therapies that reduce high Lp(a) levels by at least 80 nmol/L (≈40%) may be needed to produce worthwhile benefits in people at the highest risk because of Lp(a). CLINICAL
trial registrationURL: https://clinicaltrials.gov. Unique identifier: NCT00461630.
Indexed as
Hypolipidemic AgentsIndolesLipoprotein(a)NiacinProtein IsoformsSimvastatinAgedCoronary DiseaseFemaleHumansMaleMiddle AgedRisk FactorsHypolipidemic AgentsIndolesLipoprotein(a)MK-0524NiacinProtein IsoformsSimvastatinapolipoprotein(a)clinical trialcoronary diseaseisoform sizelipoprotein(a)therapeutics
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Registered trials
NCT00461630ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.