Evidence mapPaperPMID 42395082Full record

ArticleAmerican journal of preventive cardiology2026

Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials.

Aditya Karthikeyan, Avrohom Karp, Maisha Maliha, Amrin Kharawala, Sridhar Mangalesh, Priyansh Shah, Vishakha Modak, Adir Alper, Apoorva Doshi, Hamsa Murli and 3 more

Abstract read
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Article in American journal of preventive cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Aditya KarthikeyanDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Avrohom KarpDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Maisha MalihaDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Amrin KharawalaDivision of Cardiology, Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Sridhar MangaleshDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Priyansh ShahDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Vishakha ModakDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Adir AlperDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Apoorva DoshiDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Hamsa MurliDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Vikyath SatishDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Kuan-Yu ChiDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.
Robert T FaillaceDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an established strategy to lower low-density lipoprotein cholesterol (LDL-C) and reduce atherosclerotic cardiovascular disease risk. Recently developed oral PCSK9 inhibitors may be a user-friendly alternative. Methods: A systematic search from inception through March 6, 2026, identified randomized controlled trials comparing oral PCSK9 inhibitors with placebo in adults with established atherosclerotic cardiovascular disease or at high risk of atherosclerotic cardiovascular disease, receiving background lipid-lowering therapy, or with statin intolerance. The efficacy endpoint was percentage change in lipid levels including LDL-C, apolipoprotein-B, lipoprotein(a), triglycerides, and non-HDL-C. Safety outcomes included any adverse event, serious adverse events, discontinuation due to adverse events, and new-onset or worsening of diabetes attributed to intervention. Random-effects meta-analysis was performed using restricted-maximum-likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment. Heterogeneity was assessed using I² statistic. Results: Across five randomized phase 2 and 3 trials (n = 4226), oral PCSK9 inhibitors were associated with a significant reduction in LDL-C versus placebo (mean difference -49.92%; 95% CI -56.41 to -43.43; I² = 86%; PI, -72.30 to -27.54). Significant reductions were also observed in ApoB, Lp(a), triglycerides, and non-HDL-C. Safety outcomes were similar between both groups. In dose-matched analyses of MK-0616 at comparable dosing across trials, reductions in lipid markers remained significant with minimal heterogeneity. Conclusions: Oral PCSK9 inhibitors were associated with reductions in LDL-C, ApoB, non-HDL-C, and lipoprotein(a), with safety profile comparable to placebo. Longer-term studies evaluating cardiovascular outcomes and comparisons with injectable PCSK9 inhibitors are required to define their clinical role.

Indexed as

LDL-COral PCSK9 inhibitorPlacebo

Identifiers

PMID42395082
PMCPMC13326082

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.