Living Knowledge · Confidence Timeline

alirocumab lowers LDL cholesterol in hyperlipidaemia

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

Confidence
82%
Uncertainty 74%–91% (±8%)
Evidence coverage
Broad91%
22 evidence families3 independent 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
    ±8% → ±8%
    Coverage
    91% → 91%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 91%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±8% → ±8%
    Coverage
    91% → 91%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 91%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±8% → ±8%
    Coverage
    90% → 91%

    Confidence increased by 1 point to 82% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 91%.

  • Quiet period7 Nov 2018 – 1 Nov 2019
    No confidence movement
    Coverage 95% → 90%

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

  • New supporting evidence

    Major change
    Confidence
    79% → 82%
    Uncertainty
    ±9% → ±8%
    Coverage
    95% → 95%

    Confidence increased by 2 points to 82% after 1 independent supporting evidence family was incorporated. Evidence coverage was unchanged at 95%.

    • 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
    ±9% → ±9%
    Coverage
    94% → 95%

    Confidence was unchanged at 79%. Evidence coverage was unchanged at 95%.

  • 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
    ±8% → ±9%
    Coverage
    94% → 94%

    Confidence decreased by 3 points to 79% after 1 independent supporting evidence family were incorporated. Uncertainty widened from ±8% to ±9%. Evidence coverage was unchanged at 94%.

    • 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
    ±8% → ±8%
    Coverage
    94% → 94%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 94%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±8% → ±8%
    Coverage
    94% → 94%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 94%.

  • New supporting evidence

    Confidence
    82% → 82%
    Uncertainty
    ±8% → ±8%
    Coverage
    94% → 94%

    Confidence was unchanged at 82%. Evidence coverage was unchanged at 94%.

  • Quiet period1 Oct 2016 – 1 Oct 2016
    No confidence movement
    Coverage 93% → 94%

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

  • New supporting evidence

    Major change
    Confidence
    79% → 82%
    Uncertainty
    ±9% → ±8%
    Coverage
    93% → 93%

    Confidence increased by 3 points to 82% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±9% to ±8%. Evidence coverage was unchanged at 93%.

    • Confidence increased
    • Uncertainty narrowed
  • Quiet period22 Jul 2016 – 22 Jul 2016
    No confidence movement
    Coverage 100% → 93%

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

  • New supporting evidence

    Major change
    Confidence
    78% → 79%
    Uncertainty
    ±10% → ±9%
    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
    ±10% → ±10%
    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
    ±10% → ±10%
    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
    ±12% → ±10%
    Coverage
    100% → 100%

    Confidence increased by 3 points to 78% after 2 independent supporting evidence families were incorporated. Uncertainty narrowed from ±12% to ±10%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Confidence
    74% → 74%
    Uncertainty
    ±12% → ±12%
    Coverage
    100% → 100%

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

  • New supporting evidence

    Confidence
    73% → 74%
    Uncertainty
    ±12% → ±12%
    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
    ±13% → ±12%
    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
    ±14% → ±13%
    Coverage
    100% → 100%

    Confidence increased by 2 points to 72% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±14% to ±13%. 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
    ±16% → ±14%
    Coverage
    100% → 100%

    Confidence increased by 6 points to 70% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±16% to ±14%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Major change
    Confidence
    49% → 64%
    Uncertainty
    ±31% → ±16%
    Coverage
    100% → 100%

    Confidence increased by 15 points to 64% after 1 independent supporting evidence family was incorporated. Uncertainty narrowed from ±31% to ±16%. Evidence coverage was unchanged at 100%.

    • Confidence increased
    • Uncertainty narrowed

  • New supporting evidence

    Major change
    Confidence
    0% → 49%
    Uncertainty
    ±31% → ±31%
    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
Engine methodology v1.7.0. 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.
Computed 2026-08-05 · not medical advice.