Living Knowledge · Confidence Timeline

alirocumab lowers LDL cholesterol in hyperlipidaemia

Scientific confidence changes as new graded evidence accumulates and corroboration from distinct sources is detected. This timeline shows how the evidence for this claim has evolved — what changed, why it changed, and which scientific dimension moved.

Confidence
82%
Uncertainty 73%–92% (±9%)
Evidence coverage
Broad93%
22 evidence families3 source groupsRegulatory standing: approvedLast meaningful update: 8 Apr 2020
0%50%100%
supporting no-effect contradicting coverage-only— confidence┄ evidence coverage

What changed, and why

  • Quiet period8 Oct 2021 – 24 Sep 2025
    No confidence movement

    5 evidence events retrieved. 5 were coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±9% → ±9%
    Coverage
    93% → 93%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 93%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±10% → ±9%
    Coverage
    93% → 93%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 93%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±10% → ±10%
    Coverage
    92% → 93%

    Confidence increased by 1 point to 82% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 93%.

  • Quiet period7 Nov 2018 – 1 Nov 2019
    No confidence movement
    Coverage 96% → 92%

    2 evidence events retrieved. 2 were coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Major change
    Confidence
    79% → 82%
    Uncertainty
    ±11% → ±10%
    Coverage
    96% → 96%

    Confidence increased by 2 points to 82% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 96%.

    • Confidence increased
  • Quiet period6 Aug 2018 – 6 Aug 2018
    No confidence movement

    1 evidence event retrieved. 1 was coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Confidence
    79% → 79%
    Uncertainty
    ±11% → ±11%
    Coverage
    96% → 96%

    Confidence was unchanged at 79%. Evidence coverage was unchanged at 96%.

  • Quiet period28 Jul 2017 – 28 Jul 2017
    No confidence movement

    1 evidence event retrieved. 1 was coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Major change
    Confidence
    82% → 79%
    Uncertainty
    ±9% → ±11%
    Coverage
    95% → 96%

    Confidence decreased by 3 points to 79% after 1 independent supporting evidence family were incorporated. Uncertainty widened from ±9% to ±11%. Evidence coverage was unchanged at 96%.

    • Confidence decreased
    • Uncertainty widened
  • Quiet period31 May 2017 – 31 May 2017
    No confidence movement

    1 evidence event retrieved. 1 was coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±10% → ±9%
    Coverage
    95% → 95%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 95%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±10% → ±10%
    Coverage
    95% → 95%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 95%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±10% → ±10%
    Coverage
    94% → 95%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 95%.

  • Quiet period1 Oct 2016 – 1 Oct 2016
    No confidence movement
    Coverage 94% → 94%

    1 evidence event retrieved. 1 duplicated or fell outside the claim scope.

  • New supporting evidence

    Major change
    Confidence
    79% → 82%
    Uncertainty
    ±11% → ±10%
    Coverage
    94% → 94%

    Confidence increased by 3 points to 82% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±11% to ±10%. Evidence coverage was unchanged at 94%.

    • Confidence increased
    • Uncertainty narrowed
  • Quiet period22 Jul 2016 – 22 Jul 2016
    No confidence movement
    Coverage 100% → 94%

    1 evidence event retrieved. 1 was coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Major change
    Confidence
    78% → 79%
    Uncertainty
    ±12% → ±11%
    Coverage
    100% → 100%

    Confidence increased by 1 point to 79% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 100%.

    • Confidence increased

  • New supporting evidence

    Confidence
    78% → 78%
    Uncertainty
    ±12% → ±12%
    Coverage
    100% → 100%

    Confidence was unchanged at 78%. Evidence coverage was unchanged at 100%.

  • Regulatory eventSeparate axis

    Confidence was unchanged at 78%. Evidence coverage was unchanged at 100%. 1 regulatory event was recorded on the separate regulatory-standing axis and did not change efficacy confidence.

  • New supporting evidence

    Confidence
    78% → 78%
    Uncertainty
    ±12% → ±12%
    Coverage
    100% → 100%

    Confidence was unchanged at 78%. Evidence coverage was unchanged at 100%.

  • Quiet period13 Mar 2015 – 1 Jul 2015
    No confidence movement

    5 evidence events retrieved. 3 were coverage-only (on-topic, no readable direction) and 2 duplicated or fell outside the claim scope.

  • New supporting evidence

    Major change
    Confidence
    74% → 78%
    Uncertainty
    ±13% → ±12%
    Coverage
    100% → 100%

    Confidence increased by 3 points to 78% after 2 independent supporting evidence families were incorporated. Uncertainty narrowed from ±13% to ±12%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Confidence
    74% → 74%
    Uncertainty
    ±13% → ±13%
    Coverage
    100% → 100%

    Confidence was unchanged at 74%. Evidence coverage was unchanged at 100%.

  • New supporting evidence

    Confidence
    73% → 74%
    Uncertainty
    ±14% → ±13%
    Coverage
    100% → 100%

    Confidence increased by 1 point to 74% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 100%.

  • Quiet period1 May 2014 – 31 May 2014
    No confidence movement

    2 evidence events retrieved. 2 were coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Major change
    Confidence
    72% → 73%
    Uncertainty
    ±15% → ±14%
    Coverage
    100% → 100%

    Confidence increased by 1 point to 73% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 100%.

    • Confidence increased

  • New supporting evidence

    Major change
    Confidence
    70% → 72%
    Uncertainty
    ±16% → ±15%
    Coverage
    100% → 100%

    Confidence increased by 2 points to 72% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±16% to ±15%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed
  • Quiet period1 Jan 2012 – 1 Jul 2013
    No confidence movement

    3 evidence events retrieved. 3 were coverage-only (on-topic, no readable direction).

  • New supporting evidence

    Major change
    Confidence
    64% → 70%
    Uncertainty
    ±19% → ±16%
    Coverage
    100% → 100%

    Confidence increased by 6 points to 70% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±19% to ±16%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Major change
    Confidence
    49% → 64%
    Uncertainty
    ±34% → ±19%
    Coverage
    100% → 100%

    Confidence increased by 15 points to 64% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±34% to ±19%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Major change
    Confidence
    0% → 49%
    Uncertainty
    ±34% → ±34%
    Coverage
    100%

    Confidence for this claim was first established at 49% from 1 independent supporting evidence family.

    • Confidence increased
View all evidence · 47 items in the ledger
  • trialNCT01288469 — A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed supportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis' (From Baseline to Week 8 (LOCF)): drug -66.2% vs placebo -17.3% (Δ -55.82%, p<0.0001).
  • trialNCT01266876 — A Randomized, Double-Blind, Placebo-Controlled, 12-Week Study of the SsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis' (From Baseline to Week 12 (LOCF)): drug -28.9% vs placebo -10.7% (Δ -18.2%, p=0.0113).
  • trialNCT01288443 — A Randomized, Double-blind, Parallel-group, Placebo-controlled, MulticsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis' (Baseline to Week 12 (LOCF)): drug -39.6% vs placebo -5.1% (Δ -34.5%, p<0.0001).
  • trialNCT01448317 — A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose neutralNo posted results — existence/phase are not direction.
  • trialNCT01644474 — A Randomized, Double-Blind, Active-Controlled, Parallel-Group Study toneutralResults posted but no readable target outcome — coverage only.
  • trialNCT01723735 — A Randomized, Partial Blind, 3 Parallel Groups Study of the PharmacodyneutralNo posted results — existence/phase are not direction.
  • trialNCT01812707 — A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-contrsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis' (Baseline to Week 12 (LOCF)): drug -54.8% vs placebo -2.7% (Δ -52.099999999999994%, p<0.0001).
  • trialNCT01644175 — A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis' (From Baseline to Week 52): drug -48.2% vs placebo -2.3% (Δ -45.9%, p<0.0001).
  • trialNCT01730040 — A Randomized, Double-Blind Study of the Efficacy and Safety of AlirocuneutralResults posted but no readable target outcome — coverage only.
  • trialNCT01730053 — A Randomized, Double-Blind Study of the Efficacy and Safety of REGN727neutralResults posted but no readable target outcome — coverage only.
  • trialNCT01507831 — Long-term Safety and Tolerability of SAR236553 (REGN727) in High CardisupportsStructured CT.gov secondary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis' (From Baseline to Week 52): drug -61% vs placebo +0.8% (Δ -61.9%, p<0.0001).
  • trialNCT01623115 — A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis' (From Baseline to Week 52): drug -48.8% vs placebo +9.1% (Δ -57.9%, p<0.0001).
  • trialNCT01617655 — A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis' (From Baseline to Week 52): drug -45.7% vs placebo -6.6% (Δ -39.1%, p<0.0001).
  • trialNCT01709500 — A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent--to--Treat (ITT) Analysis' (From Baseline to Week 52): drug -48.7% vs placebo +2.8% (Δ -51.4%, p<0.0001).
  • paperEfficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among supportsEffect reported but bounded (subgroup / regain / caveat) in the conclusion.
  • paperEfficacy and safety of alirocumab in reducing lipids and cardiovascular events.supportsEfficacy on the claim outcome reported in the results.
  • trialNCT01926782 — A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the EneutralResults posted but no readable target outcome — coverage only.
  • trialNCT01959971 — A Phase 1 Study of the Effects of Subcutaneous Doses of Alirocumab on neutralNo posted results — existence/phase are not direction.
  • trialNCT01644188 — A Randomized, Double-Blind, Parallel Group Study to Evaluate the EfficneutralResults posted but no readable target outcome — coverage only.
  • paperODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous supportsEfficacy on the claim outcome reported in the conclusion.
  • trialNCT02107898 — A Randomized, Double-blind, Placebo-controlled, Parallel Group, MulticsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)' (From Baseline to Week 24): drug -62.5% vs placebo +1.6% (Δ -64.1%, p<0.0001).
  • regulatoryEMA — approved—Regulatory standing (separate axis) — never inflates evidential confidence.
  • trialNCT02289963 — A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis' (From Baseline to Week 24): drug -57.1% vs placebo +6.3% (Δ -63.4%, p<0.0001).
  • trialNCT02326220 — A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study tsupportsStructured CT.gov secondary outcome 'Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6' (Baseline and at Week 6): drug -53.7% vs placebo +1.6% (Δ -55.3%, p< 0.0001).
  • paperEfficacy and Safety of Alirocumab in Japanese Patients With Heterozygous Familial HypercholesterolemneutralOn-topic, but the abstract's conclusion/results state no clear weight-loss outcome (aim, adjacent outcome, or mechanism only).
  • paperEfficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on supportsEfficacy on the claim outcome reported in the conclusion.
  • paperEfficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDsupportsEffect reported but bounded (subgroup / regain / caveat) in the conclusion.
  • trialNCT01576484 — A Phase 2, Open-Label Extension of Study R727-CL-1003 to Evaluate the supportsStructured CT.gov outcome: drug -63.4% vs placebo -73.15% — LDL cholesterol moved the right way but not clearly beyond placebo (Δ +9.750000000000007%).
  • trialNCT02585778 — A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis' (From Baseline to Week 24): drug -51.8% vs placebo -3.9% (Δ -47.8%, p<0.0001).
  • trialNCT02642159 — A Randomized, Open-Label, Parallel Group Study to Evaluate the EfficacsupportsStructured CT.gov secondary outcome 'Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis': drug arm -43.3% (vs an active comparator, not placebo).
  • trialNCT01709513 — A Randomized, Double-Blind, Double-Dummy, Active-Controlled Study to EneutralResults posted but no readable target outcome — coverage only.
  • trialNCT01954394 — Open-Label Extension Study of EFC12492, R727-CL-1112, EFC12732 and LTSsupportsStructured CT.gov outcome: drug -43.8% vs placebo -44.9% — LDL cholesterol moved the right way but not clearly beyond placebo (Δ +1.1000000000000014%).
  • trialNCT02023879 — A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study EsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)' (From Baseline to Week 24): drug -53.5% vs placebo +4.7% (Δ -56.4%, p<0.0001).
  • trialNCT01604824 — A Phase 2 Pilot Study With a Randomized Double-Blind Treatment Phase tneutralResults posted but no readable target outcome — coverage only.
  • trialNCT02584504 — A Randomized, Double-blind, Placebo-controlled, Parallel Group Study tsupportsStructured CT.gov primary outcome 'Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis' (From Baseline to Week 12): drug -70.1% vs placebo -43.8% (Δ -26.3%).
  • trialNCT02715726 — A Randomized, Double-blind, Parallel Group Study to Evaluate the EfficneutralResults posted but no readable target outcome — coverage only.
  • trialNCT02938949 — Alirocumab in Patients With Acute Myocardial Infarction: A Randomized supportsStructured CT.gov primary outcome 'Changes in Low-density Lipoprotein (LDL) Cholesterol' (baseline and 14 days): drug -73% vs placebo +2% (Δ -75%, p<0.01) — only N=20, down-weighted.
  • paperAlirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome.neutralOn-topic, but the abstract's conclusion/results state no clear weight-loss outcome (aim, adjacent outcome, or mechanism only).
  • trialNCT02992301 — Assessment of Atherosclerotic Plaque Characteristics Change by DCE-MRIneutralNo posted results — existence/phase are not direction.
  • trialNCT03156621 — A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study tsupportsStructured CT.gov primary outcome 'Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 (Intent-to-Treat [ITT] Estimand)' (Baseline to Week 12): drug -26.9% vs placebo +8.6% (Δ -35.6%, p<0.0001).
  • trialNCT02957682 — A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the EsupportsStructured CT.gov secondary outcome 'Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) at Week 12, 24, 48, 72, and 96' (Week 12, 24, 48, 72, and 96): drug -49.6% vs placebo +0.6% (Δ -50.2%).
  • trialNCT03694197 — Long Term Safety Study of PRALUENT in Patients With Heterozygous FamilsupportsStructured CT.gov secondary outcome 'Percent Change in LDL-C From Baseline Over Time': drug arm -48.74% (single-arm, no control).
  • trialNCT03718286 — Effects of Acute, Rapid Lowering of Low Density Lipoprotein CholesteroneutralNo posted results — existence/phase are not direction.
  • trialNCT03750760 — Early Alirocumab to Reduce LDL-C in Myocardial InfarctionneutralNo posted results — existence/phase are not direction.
  • trialNCT05465278 — Clinical Trial to Evaluate the Effect of Alirocumab on the Volume, ArcneutralNo posted results — existence/phase are not direction.
  • trialNCT04790513 — Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and SafneutralNo posted results — existence/phase are not direction.
  • trialNCT03207945 — Effect of PCSK9 Inhibition on Cardiovascular Risk in Treated HIV InfecneutralNo posted results — existence/phase are not direction.
View methodology and known limitations
Scored by Confidence Engine methodology v1.11.0 (snapshot build 10 — a cache generation, not a methodology version). Methodology-version changes are recorded separately from new evidence; a change in engine version reinterprets existing evidence and is not a new scientific discovery.
  • Engine constants are calibrated against a small anchor set — coarse, not authoritative.
  • Evidence is skewed toward the drug's sponsor; genuinely independent replication is the honest ceiling.
  • Paper direction is extracted from abstracts; the hedged tail stays neutral (coverage, not confidence).
  • Regulatory approval is tracked on a separate axis and never inflates evidential confidence.
Full methodology & known limitations →
Computed 2026-09-20 · not medical advice.