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Cited by 216Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Effect of Vupanorsen on Non–High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70

Open access
Bergmark, Brian A., Marston, Nicholas A., Bramson, Candace R., Curto, Madelyn, Ramos, Vesper, Jevne, Alexandra, Kuder, Julia F., Park, Jeong-Gun +60 more·2022·Circulation
DOI 10.1161/circulationaha.122.059266PMC PMC9047643
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Abstract

Background: Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. Methods: Adults with non–high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non–HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3. Results: Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58–69) years, 44% were female, the median non–HDL-C was 132.4 (interquartile range, 118.0–154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4–270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non–HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all P <0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all P <0.001). The effects on LDL-C and ApoB were more modest (7.9%–16.0% and 6.0%–15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all P <0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%). Conclusions: Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non–HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic fat fraction. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT04516291.

AI snapshot

Written from the paper’s full text.

TL;DR

In statin-treated adults with elevated non-HDL-C and triglycerides, vupanorsen significantly reduced non-HDL-C at all studied doses over 24 weeks. Higher total monthly doses were associated with more injection site reactions, liver enzyme elevations, and dose-dependent increases in hepatic fat fraction.

Key findings

  • Vupanorsen produced placebo-adjusted reductions in non-HDL-C from 22.0% (60 mg every 2 weeks) to 27.7% (80 mg every 2 weeks) at 24 weeks (all P<0.001).
  • Triglycerides fell dose-dependently by 41.3% to 56.8% (all P<0.001), while ANGPTL3 decreased by 69.9% to 95.2% (all P<0.001).
  • LDL-C and ApoB effects were more modest (7.9%–16.0% and 6.0%–15.1%, respectively), without a clear dose-response, and only the higher reductions reached statistical significance.
  • Safety signals included injection site reactions in 49 (20.2%) vupanorsen-treated vs 2 (4.5%) placebo-treated patients, ALT/AST >3× ULN in up to 44.4% at the highest dose, and a dose-dependent hepatic fat fraction increase up to 76% relative at 160 mg every 2 weeks.

Methods

  • Phase 2b double-blind, randomized, placebo-controlled trial at 55 sites in 3 countries from October 2020 through April 2021; 286 subjects were randomized (44 placebo, 242 vupanorsen) to 7 vupanorsen dose regimens or placebo.
  • Eligible patients were statin-treated adults ≥40 years old with non-HDL-C ≥100 mg/dL and triglycerides 150–500 mg/dL; key exclusions included active liver disease other than steatosis, HbA1c ≥9.5%, eGFR <30 mL/min/1.73 m², ALT/AST >2× ULN, or low platelet count.
  • Primary end point was placebo-adjusted percentage change in non-HDL-C at 24 weeks; comparisons used a mixed model for repeated measures with placebo-adjusted least squares mean differences and 95% CIs, without adjustment for multiple testing.

Limitations

  • Stated: the trial population was intended to reflect a large cardiovascular outcomes trial, so findings may not generalize to patients with specific lipid disorders; genetic testing for lipid disorders was not performed.
  • Stated: although powered for the primary end point, a larger study would have allowed more precise assessment of the relationship between non-HDL-C and ANGPTL3 reductions across dose regimens; non-White subjects were underrepresented (13% vs approximately 23% in the weighted overall populations of participating countries).
  • Evident from the text: there was no adjustment for multiple testing, and premature study drug discontinuation was much more frequent with vupanorsen (24.0%) than placebo (4.5%), mostly due to adverse events (43/60, 71.7%), which may affect interpretation of tolerability and longer-term effects.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1161/circulationaha.122.059266

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingreasoning

    Reductions in triglycerides with vupanorsen showed a dose-response relationship.

    “Conversely, reductions in triglycerides with vupanorsen showed a dose-response relationship, mirroring the reduction in ANGPTL3 and consistent with the expected increases in lipoprotein lipase activity.”
    Quote in the paperNot a substantial claim
  • Findingown data

    A total of 19 (6.6%) subjects experienced a treatment-emergent serious adverse event.

    “A total of 19 (6.6%) subjects experienced a treatment-emergent serious adverse event.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Reduction in ANGPTL3 levels increased with total monthly vupanorsen dose.

    “whereas the reduction in ANGPTL3 levels increased with total monthly dose, there was no clear dose-response reduction in LDL-C or ApoB.”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was a dose-related increase in hepatic fat fraction with vupanorsen.

    “More frequent elevations of ALT or AST occurred at higher total monthly vupanorsen doses, and there was a dose-related increase in hepatic fat fraction.”
    • Also stated in: § Conclusions · plain
      “Key safety findings included more frequent liver enzyme elevations at higher total monthly doses and a dose-related increase in hepatic fat fraction.”
    Quote in the paperSubstantial claim
  • Findingown data

    Elevations of ALT or AST >3× ULN were more common at higher total monthly doses of vupanorsen, up to 44.4%.

    “Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively)”
    • Also stated in: § Safety and Tolerability · hedged
      “Elevations in ALT or AST >3× the upper limit of normal were more common with vupanorsen than placebo and tended to be more common at higher total monthly doses, with 16 (44.4%)subjects in the 160 mg every 2 weeks arm having any instance of an ALT or AST value reaching this threshold, and 14 (38.9%)having an abnormal repeat value within 7 days.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Findingown data

    Reductions in non-HDL-C were evident within 4 weeks of treatment initiation and persisted through the study period.

    “Reductions in non-HDL-C were evident within 4 weeks of treatment initiation and persisted through the study period (Figure S3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No serious adverse event was deemed related to study medication by the investigator, and there were no suspected unexpected serious adverse reactions.

    “No serious adverse event was deemed related to study medication by the investigator, and there were no suspected unexpected serious adverse reactions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no elevations in bilirubin or Hy's law cases among vupanorsen-treated subjects.

    “There were no elevations in bilirubin or Hy's law cases among vupanorsen-treated subjects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen.

    “There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen.”
    • Also stated in: § Safety and Tolerability · plain
      “There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Vupanorsen reduced ApoB placebo-adjusted at 24 weeks by 6.0% to 15.1%, with only the higher reductions achieving statistical significance and no clear dose-response relationship.

    “The effects on LDL-C and ApoB were more modest (7.9%-16.0%and 6.0%-15.1%,respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance.”
    • Also stated in: § Effect of Vupanorsen · plain
      “The effects of vupanorsen on LDL-C and ApoB were more modest and without a clear dose-response (Figure 2 and Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Antidrug antibodies were observed in 73 (30.2%) vupanorsen-treated patients, with no apparent difference in treatment effect in those with versus without antidrug antibodies.

    “Antidrug antibodies were observed in 73 (30.2%) vupanorsen-treated patients, with no apparent difference in treatment effect in those with versus without antidrug antibodies (Table S3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Vupanorsen reduced LDL-C placebo-adjusted at 24 weeks by 7.9% to 16.0%, with only the higher reductions achieving statistical significance and no clear dose-response relationship.

    “The effects on LDL-C and ApoB were more modest (7.9%-16.0%and 6.0%-15.1%,respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance.”
    • Also stated in: § Effect of Vupanorsen · plain
      “The effects of vupanorsen on LDL-C and ApoB were more modest and without a clear dose-response (Figure 2 and Table 2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    No consistent associations have been observed between circulating ANGPTL3 levels and hepatic steatosis.

    “Nonetheless, ANGPTL3 inhibition in mice with an antisense oligonucleotide led to a reduction in liver triglyceride content, 8 and no consistent associations have been observed between ANGPTL3 loss-of-function mutations and liver disease 8,13 or between circulating ANG-PTL3 levels and hepatic steatosis.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The trial aimed to enroll 260 subjects to account for potential dropout.

    “To account for potential dropout, we aimed to enroll 260 subjects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Among subjects assigned to vupanorsen, 58 (24.0%) permanently stopped study drug prematurely, compared with 2 (4.5%) among placebo.

    “Among subjects assigned to placebo, 2 (4.5%) permanently stopped study drug prematurely, and among subjects assigned to vupanorsen, 58 (24.0%) permanently stopped study drug prematurely (Figure S1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    All patients received at least 1 dose of study drug, 2 (0.7%) withdrew consent, and 1 (0.3%) was lost to follow-up.

    “All patients received at least 1 dose of study drug, 2 (0.7%) withdrew consent, and 1 (0.3%) was lost to follow-up (Figure S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Substantial residual cardiovascular risk remains despite lipid-lowering therapies, for which numerous promising therapeutic targets are under investigation.

    “However, substantial residual risk remains, for which numerous promising therapeutic targets are under investigation.11”
    • Also stated in: § What Are the Clinical Implications? · plain
      “Despite recent advances in lipid-modifying therapy, residual cardiovascular risk remains in many patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits ANGPTL3 protein synthesis.

    “Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The observed interaction between vupanorsen effect and patient sex cannot be determined to reflect a true biological difference rather than chance.

    “The effect of vupanorsen on non-HDL-C was generally consistent across key clinical subgroups, and it is not clear if the observed interaction between vupanorsen effect and patient sex reflects a true biological difference or is simply a result of chance.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All analyses were performed by the TIMI Study Group on a complete, independently held database using SAS version 9.4.

    “All analyses were performed by the TIMI Study Group on a complete, independently held database using commercially available software (SAS, version 9.4, Cary, NC).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters.

    “Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ANGPTL3 inhibition in mice with an antisense oligonucleotide led to a reduction in liver triglyceride content.

    “Nonetheless, ANGPTL3 inhibition in mice with an antisense oligonucleotide led to a reduction in liver triglyceride content, 8 and no consistent associations have been observed between ANGPTL3 loss-of-function mutations and liver disease 8,13 or between circulating ANG-PTL3 levels and hepatic steatosis.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids, including lower triglycerides and LDL-C, and with lower rates of coronary artery disease.

    “Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids.”
    • Also stated in: § DISCUSSION · plain
      “In genetic studies, loss-of-function variants in ANGPTL3 have been associated with lower levels of triglycerides and LDL-C and with lower rates of coronary artery disease.7,9,12”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] source

      Not checked in the free run.

    • cites [9] source

      Not checked in the free run.

    • cites [12] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The study population reflects a typical cohort intended for cardiovascular risk reduction, with type 2 diabetes in approximately one-half of patients and prevalent atherosclerotic cardiovascular disease in a substantial portion.

    “This effect of vupanorsen was observed on a background of statin therapy, including in those on a high-intensity statin regimen, and the study population reflects a typical cohort intended for cardiovascular risk reduction, with type 2 diabetes in approximately one-half of patients and prevalent atherosclerotic cardiovascular disease in a substantial portion.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    There was no adjustment for multiple testing.

    “There was no adjustment for multiple testing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    A total of 286 subjects were randomized at 55 sites in 3 countries from October 2020 through April 2021.

    “A total of 286 subjects were randomized at 55 sites in 3 countries (Supplemental Material) from October 2020 through April 2021.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    It is unclear whether the increases in hepatic fat fraction and liver enzymes reflect a metabolic effect of vupanorsen specifically or an off-target effect as a result of hepatic targeting of ANGPTL3.

    “Ultimately, it is unclear whether the increases in hepatic fat fraction and liver enzymes reflect a metabolic effect of vupanorsen specifically or an off-target effect as a result of hepatic targeting of ANGPTL3.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    An antisense oligonucleotide targeting apolipoprotein C3 has shown reductions in triglycerides up to 77% and in ApoB up to 30% in healthy volunteers without major safety concerns.

    “An antisense oligonucleotide targeting apolipoprotein C3, for example, has shown reductions in triglycerides up to 77% and in ApoB up to 30% in healthy volunteers without major safety concerns, 22 although the reductions in ApoB seen in patients with hypertriglyceridemia have been of lower magnitude.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reduced renal function and platelet count have been observed with some first-generation antisense oligonucleotides.

    “With regard to safety, there were no confirmed instances of reduced renal function or platelet count with vupanorsen, 2 issues that have been observed with some first-generation antisense oligonucleotides.16,17”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] source

      Not checked in the free run.

    • cites [17] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous genetic studies have suggested that reductions in LDL-C and ApoB require near-complete suppression of ANGPTL3 activity.

    “Although previous genetic studies have suggested that reductions in LDL-C and ApoB require near-complete suppression of ANGPTL3 activity, 7,13 we did not observe a consistent dose-response relationship for these measures.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] source

      Not checked in the free run.

    • cites [13] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recall injection site reactions have been reported with mipomersen, an antisense oligonucleotide targeting ApoB.

    “Injection site reactions were more common at higher total monthly doses, as were recall injection site reactions, which have not previously been seen with vupanorsen, but have been reported with mipomersen, an antisense oligonucleotide targeting ApoB.18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Of the 60 premature study drug discontinuations, 43 (71.7%) were a result of an adverse event.

    “Of the 60 premature study drug discontinuations, 43 (71.7%) were a result of an adverse event, and the remainder for other reasons.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study protocol was approved by all relevant ethical oversight committees, and all subjects provided written, informed consent.

    “The study protocol was approved by all relevant ethical oversight committees, and all subjects provided written, informed consent.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Reductions in ApoB seen in patients with hypertriglyceridemia have been of lower magnitude.

    “An antisense oligonucleotide targeting apolipoprotein C3, for example, has shown reductions in triglycerides up to 77% and in ApoB up to 30% in healthy volunteers without major safety concerns, 22 although the reductions in ApoB seen in patients with hypertriglyceridemia have been of lower magnitude.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    A larger study would have allowed for a more precise assessment of the relationship between non-HDL-C and ANGPTL3 reductions across dose regimens.

    “Second, although the trial did have adequate power for its primary end point, a larger study would have allowed for a more precise assessment of the relationship between non-HDL-C and ANGPTL3 reductions across dose regimens.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Testing for genetic disorders of lipid metabolism was not performed.

    “Testing for genetic disorders of lipid metabolism was not performed.”
    Quote in the paperNot a substantial claim
31 of 31

  • The paper relies on this without support.

    ANGPTL3 inhibits lipases, including lipoprotein lipase, and impairs metabolism of triglyceride-rich lipoproteins.

    “Among these is ANGPTL3, a hepatically produced protein that inhibits lipases, including lipoprotein lipase, and impairs metabolism of triglyceride-rich lipoproteins.”

  • The paper relies on this without support.

    A potential cardiovascular benefit of vupanorsen would best be reflected by its effects on non-HDL-C and ApoB.

    “Given that a potential cardiovascular benefit of vupanorsen would best be reflected by its effects on non-HDL-C and ApoB, we designed the TRANSLATE-TIMI 70 trial to assess these parameters at higher doses than had been evaluated in the phase 2a study.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Hypertriglyceridemia is common and is associated with an increased risk of atherosclerosis.

    “H ypertriglyceridemia is common and is associated with an increased risk of atherosclerosis, 1-4”

    From Targeting <i>APOC3</i> with Olezarsen in Moderate Hypertriglyceridemia (2025) · cites this paper as [3]

    The Discussion reports that ANGPTL3 loss-of-function variants are associated with both lower triglycerides and lower coronary artery disease rates, but it does not establish an association between hypertriglyceridemia and atherosclerosis. The passages searched for prevalence, elevated triglycerides, and atherosclerotic risk also do not say that hypertriglyceridemia is common. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

The citation lists haven’t been fetched yet

References 22 · Cited by 216

Research works printed but not linked: 1

  1. Marston, NA, Giugliano, RP, Melloni, GEM, Park, JG, Morrill, V, Blazing, MA, Ference, B, Stein, E, Stroes, ES, Braunwald, E, et al. Association of apolipoprotein B-containing lipoproteins and risk of myocardial infarction in individuals with and without atherosclerosis: distinguishing between particle concentration, type, and content. JAMA Cardiol. 2022;7:250–256.

Authors
Bergmark, B. A., Marston, N. A., Bramson, C. R., Curto, M., Ramos, V., Jevne, A., Kuder, J. F., Park, J.-G., Murphy, S. A., Verma, S., Wojakowski, W., Terra, S. G., Sabatine, M. S., Wiviott, S. D., Carbonneau, D., Poulin-Robitaille, R., Wayne, J., Lee, K., Mujica Trenche, S., Dzongowski, P., Gaudet, D., Van, J., Ajani, D., Bays, H., O’Mahony, J., Janas, A., Scott, J., Moustafa, M. A., Ransom, T., Benjamin, S., Aggarwal, N., Bogdanski, P., Friars, D., Schlosser, R., Okopien, B., Budhraja, M., Feld, L., Klaff, L., Tellier, G., Mazza, G., Wierzbicka, I., Jazwinska-Tarnawska, E., Boccalandro, F., Rosenstock, J., Marquez, E., Barbel-Johnson, K., Madziarska, K., Heaton, K., Tardif, J.-C., Rubino, J., Trevino, M., Moriarty, K., Gupta, A., Wojakowski, W., Fidelholtz, J., Gupta, D., Alasaad, H., Christensen, S., Shah, P., Li, S., Sherman, M., Frechette, A., Arango, C., Egan, A., Srivastava, S., Bajaj, A., Ince Jr, C., & Zurakowski, A.
Affiliations
  • Brigham and Women's Hospital (US)
  • Pfizer (United States) (US)
  • University of Toronto (CA)
  • Medical University of Silesia (PL)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-05-03
Volume
145
Issue
18
Pages
1377-1386
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.122.059266
PMC
PMC9047643
OpenAlex
W4225261270
Semantic Scholar
467456b4310872c59409a378e93b4fd2074cb564
Cited by
216
References
22
Citations by year
2026: 44 · 2025: 41 · 2024: 56 · 2023: 51 · 2022: 24
FWCI
41.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Circulation (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (K08HL153950)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
ANGPTL3, antisense oligonucleotides, non-HDL cholesterol, triglycerides, hypertriglyceridemia, LDL cholesterol, apolipoprotein B, dose-response relationship, lipoprotein metabolism
MeSH terms
Injection Site Reaction, Angiopoietin-like Proteins, Angiopoietin-Like Protein 3, Adult, Apolipoproteins B, Cholesterol, Double-Blind Method, Female, Humans, Hypercholesterolemia, Lipoproteins, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Triglycerides, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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