Praluent (Alirocumab)
Indications
Alirocumab is a PCSK9-inhibiting monoclonal antibody marketed in the United States since 2015. The current FDA prescribing information (revised October 2025) lists the following approved indications. Among PCSK9 inhibitors, alirocumab is distinguished by an FDA-approved paediatric indication beginning at age 8 years for HeFH and by its evidence base in the post–acute coronary syndrome population from ODYSSEY OUTCOMES.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| MACE risk reduction — reducing risk of CHD death, MI, stroke, and unstable angina requiring hospitalisation | Adults at increased risk for these events | Used in conjunction with diet and exercise; outcomes evidence is in patients with recent ACS on statin therapy | FDA Approved |
| Hypercholesterolaemia (incl. HeFH) — to reduce LDL-C | Adults | Adjunct to diet and exercise | FDA Approved |
| Heterozygous familial hypercholesterolaemia (HeFH) — paediatric | Paediatric patients aged 8 years and older | Adjunct to diet and other LDL-C–lowering therapies | FDA Approved (March 2024) |
| Homozygous familial hypercholesterolaemia (HoFH) — to reduce LDL-C | Adults | Adjunct to diet and other LDL-C–lowering therapies | FDA Approved |
The MACE-reduction indication is supported by the ODYSSEY OUTCOMES trial: 18,924 adults with an acute coronary syndrome event 4–52 weeks before randomisation, on statin-intensive or maximally tolerated statin therapy, randomised 1:1 to alirocumab or placebo and followed for a median of 33 months. The primary composite endpoint occurred in 9.5% of alirocumab-treated patients versus 11.1% on placebo (hazard ratio 0.85, 95% CI 0.78–0.93, p=0.0003). All-cause mortality occurred in 3.5% versus 4.1% (HR 0.85, 95% CI 0.73–0.98); the prescribing information explicitly notes that this mortality finding was not statistically significant per the pre-specified method to control for type I error.
Statin intolerance with high cardiovascular risk — alirocumab has been studied in patients with confirmed statin-associated muscle symptoms (ODYSSEY ALTERNATIVE). The label’s broad MACE-risk wording (“adults at increased risk”) covers most such patients within label. Evidence quality: moderate.
Lipoprotein(a) reduction — alirocumab lowers Lp(a); whether this contributes independently to outcome benefit is unproven. Evidence quality: low.
Paediatric HoFH — alirocumab is not FDA-approved for HoFH in children; evolocumab carries this indication for patients ≥10 years. Evidence quality: insufficient for alirocumab.
Paediatric use under age 8 — safety and efficacy not established. Evidence quality: insufficient.
Dosing
| Clinical Scenario | Starting Dose | Up-Titration | Maximum Dose | Notes |
|---|---|---|---|---|
| Adults — hypercholesterolaemia (incl. HeFH); MACE risk reduction | 75 mg SC every 2 weeks or 300 mg SC every 4 weeks | If LDL-C response inadequate: 150 mg SC every 2 weeks | 150 mg every 2 weeks | Per the 2025 PI, both starting regimens are equally recommended. Reassess LDL-C 4–8 weeks after initiation or up-titration For 300 mg every 4 weeks, measure LDL-C just before next dose to capture trough |
| Adults — HeFH undergoing LDL apheresis or HoFH | 150 mg SC every 2 weeks | — | 150 mg every 2 weeks | The PI groups these scenarios together at this dose. Alirocumab can be given without regard to apheresis timing — a practical advantage over evolocumab |
| Paediatric HeFH (≥8 years), <50 kg | 150 mg SC every 4 weeks | If LDL-C response inadequate: 75 mg SC every 2 weeks | 75 mg every 2 weeks (in this weight band) | Children 8–11 years: caregiver administration after training. Adolescents 12–17 years: by or under adult supervision Reassess LDL-C 4–8 weeks after dose change |
| Paediatric HeFH (≥8 years), ≥50 kg | 300 mg SC every 4 weeks | If LDL-C response inadequate: 150 mg SC every 2 weeks | 150 mg every 2 weeks | Administer the 300 mg dose as two 150 mg pen injections at two different sites |
| Missed dose — every-2-week regimen | If within 7 days of the missed dose, administer and resume the original schedule. If >7 days late, skip and give the next dose at the regularly scheduled time | Do not double-dose to compensate | ||
| Missed dose — every-4-week regimen | If within 7 days of the missed dose, administer and resume the original schedule. If >7 days late, give the dose now and start a new monthly schedule from that date | Do not double-dose to compensate | ||
Population-Specific Considerations
| Population | Adjustment | Rationale |
|---|---|---|
| Renal impairment — mild to moderate | No adjustment | Cleared by reticuloendothelial protein catabolism; not renally excreted |
| Renal impairment — severe | No data; use with caution | Pharmacokinetics not formally characterised; mechanistic concern minimal for an IgG antibody |
| Hepatic impairment — Child-Pugh A or B | No adjustment | Single-dose PK profile similar to patients with normal hepatic function |
| Hepatic impairment — Child-Pugh C (severe) | No data available | Not formally characterised; use with caution |
| Elderly (≥65 years) | No adjustment | 3,663 patients ≥65 years (and 734 patients ≥75 years) included in controlled trials with no overall difference in safety or efficacy |
| Paediatric <8 years | Not recommended | Safety and efficacy not established |
| Pregnancy | Use only if benefit clearly outweighs risk | IgG crosses the placenta in increasing amounts in 2nd and 3rd trimester; pregnancy registry available (1-844-734-6643) |
For adults with hypercholesterolaemia, the current PI presents 75 mg every 2 weeks and 300 mg every 4 weeks as co-equal starting options. The every-2-week regimen offers more granular up-titration to 150 mg q2wk based on LDL-C response and aligns with the regimen used in ODYSSEY OUTCOMES. The every-4-week regimen reduces injection days but requires two separate 150 mg injections at each visit and produces somewhat more LDL-C variability across the dosing interval. For adults with HoFH or HeFH undergoing LDL apheresis, start at 150 mg every 2 weeks — the higher dose is the recommended starting (and only) regimen for these scenarios.
Pharmacology
Mechanism of Action
Alirocumab is a human IgG1 monoclonal antibody, produced by recombinant DNA technology in Chinese hamster ovary cells, that binds with high affinity to circulating proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 normally tags hepatic LDL receptors for lysosomal degradation; by neutralising free plasma PCSK9, alirocumab allows more LDL receptors to recycle to the hepatocyte surface, increasing clearance of LDL-cholesterol from the bloodstream.
Following a single subcutaneous dose of 75 mg or 150 mg, maximal suppression of free plasma PCSK9 occurs within 4–8 hours. In adults with hypercholesterolaemia receiving maximally tolerated statin therapy, alirocumab 150 mg every 2 weeks reduced LDL-C by approximately 58% versus placebo at 24 weeks (ODYSSEY LONG TERM); 75 mg every 2 weeks with optional up-titration to 150 mg q2wk reduced LDL-C by approximately 54% in HeFH patients (ODYSSEY FH I/FH II pooled). Modest reductions in apolipoprotein B (~50%), non-HDL cholesterol (~50%), and lipoprotein(a) are also observed.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Subcutaneous bioavailability ~85% (population PK); Tmax 3–7 days; steady state reached after 2–3 doses with accumulation ratio up to ~2-fold | Onset of LDL-C lowering measurable as early as 4 weeks; full effect within ~8 weeks |
| Distribution | Volume of distribution approximately 0.04–0.05 L/kg following IV administration — primarily intravascular | Limited tissue penetration; effects restricted to extracellular PCSK9 in plasma |
| Metabolism | Two-phase elimination: saturable target-mediated binding to PCSK9 at low concentrations; non-saturable proteolytic catabolism at higher concentrations. No CYP involvement; alirocumab does not affect statin pharmacokinetics | Drug-drug interactions via cytochrome enzymes, P-glycoprotein, or OATP transporters are not expected |
| Elimination | Median apparent half-life at steady state of 17–20 days; reduced to ~12 days when co-administered with a statin | Half-life supports every-2-week or every-4-week dosing. Population PK shows no significant influence of age, weight, sex, race, or creatinine clearance |
As with other PCSK9 antibodies, statins increase circulating PCSK9 and shorten alirocumab’s apparent half-life through enhanced target-mediated clearance. The reduction from approximately 17–20 days to about 12 days is not clinically meaningful per the FDA PI — patients on statins still achieve substantial additional LDL-C reduction with alirocumab and reach lower absolute LDL-C levels than either drug alone. No dose adjustment is required when adding alirocumab to background statin therapy.
Side Effects
Alirocumab is generally well tolerated. The most distinctive safety considerations are local injection-site reactions, hypersensitivity-type reactions (which uncommonly include serious manifestations such as hypersensitivity vasculitis), a small excess of liver-enzyme abnormalities, and a measurable rate of anti-drug antibody formation. The figures below are drawn directly from the FDA prescribing information (s047, October 2025).
| Adverse Effect | Incidence (Alirocumab vs Placebo) | Clinical Note |
|---|---|---|
| Local injection-site reaction (erythema, itching, swelling, pain/tenderness) | 7% vs 5% | Most common in the first 1–2 doses. Higher rate in patients who develop anti-drug antibodies (7.5% vs 3.6% without ADA). In the 48-week trial of 300 mg q4wk versus 75 mg q2wk, ISR rates were 16.6% (300 mg q4wk), 9.6% (75 mg q2wk), and 7.9% (placebo). |
| Influenza | 6% vs 5% | Distinguish from injection-site reaction by absence of local findings; manage with usual supportive care. |
| Diarrhoea | 5% vs 4% | Usually mild and self-limited. |
| Myalgia | 4% vs 3% | Distinguish from concomitant statin-related myalgia by trial of holding the suspected drug. |
| Muscle spasms | 3% vs 2% | Generally mild and not dose-limiting. |
| Contusion | 2% vs 1% | Particularly at injection sites; rotate sites and avoid bruised areas. |
| Adverse Effect | Incidence (Alirocumab vs Placebo) | Clinical Note |
|---|---|---|
| Myalgia | 6% vs 5% | The only adverse reaction the PI identifies as occurring in >5% of alirocumab-treated patients and more frequently than placebo in this trial. |
| Local injection-site reaction | 3.8% vs 2.1% | Led to permanent discontinuation in 26 patients (0.3%) on alirocumab versus 3 (<0.1%) on placebo. |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Hypersensitivity reactions overall (adults) | 8.6% vs 7.8% placebo | Variable | Most are mild; pruritus most common (1.1% vs 0.4%). Discontinue if severe |
| Hypersensitivity vasculitis | Reported in clinical trials (PI-listed serious allergic reaction) | Variable | Permanent discontinuation; histopathologic confirmation may be appropriate |
| Nummular eczema | Reported in clinical trials (PI-listed serious allergic reaction) | Variable | Discontinue if severe; dermatology referral for confirmation |
| Angioedema | Identified in post-marketing reports | Minutes to hours of injection | Permanent discontinuation; emergency assessment |
| Influenza-like illness | Identified in post-marketing reports | Variable | Supportive care; reassessment if persistent or severe |
| Liver-related disorders (primarily transaminase elevations) | 2.5% vs 1.8% placebo; ALT/AST >3× ULN in 1.7% vs 1.4% | Within first months | Led to discontinuation in 0.4% vs 0.2%. Routine LFT monitoring not mandated by the PI but may be appropriate when other hepatotoxic agents are co-administered |
| Anti-drug antibodies (adults, ODYSSEY OUTCOMES) | 5.5% (504/9,091) | Within first months | Some patients with persistent or neutralising antibodies showed attenuated LDL-C response. Routine ADA testing not recommended |
| Neutralising antibodies (adults, ODYSSEY OUTCOMES) | 0.5% (43/9,091); 8.5% of ADA-positive patients | Variable | Consider when LDL-C response unexpectedly attenuates despite confirmed adherence |
| Anti-drug antibodies (paediatric HeFH trial) | 3% (3/98); no neutralising antibodies detected | Within first 24 weeks | Insufficient data to define long-term consequences in paediatric patients |
| Local injection-site reaction (paediatric) | 5% vs 0% placebo | Within first doses | No paediatric patient discontinued treatment due to ISR in the pivotal trial |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Allergic reactions | 0.6% vs 0.2% placebo (pooled trials) | Most common pharmacology-specific reason. Severe reactions mandate permanent discontinuation. |
| Elevated liver enzymes | 0.3% vs <0.1% placebo (pooled trials) | Small absolute excess; mechanism not established for IgG antibodies. |
| Local injection-site reaction (CV outcomes trial) | 0.3% (26/9,451) vs <0.1% (3/9,443) | Often resolves with site rotation, allowing the pen to reach room temperature, and topical care. |
| Loss of efficacy attributed to anti-drug antibodies | Uncommon | Some adult patients with persistent or neutralising ADA experienced attenuated LDL-C response. |
Most local injection-site reactions resolve within 24–48 hours. Standard mitigation: bring the pre-filled pen to room temperature for 30–40 minutes before injection, rotate sites between abdomen, thigh, and upper arm, and avoid injecting into bruised, red, tender, or indurated tissue. Topical hydrocortisone or oral antihistamine helps for persistent erythema. Importantly — and unlike most lipid-lowering agents — alirocumab carries specific FDA labelling for hypersensitivity reactions including hypersensitivity vasculitis and angioedema, requiring permanent discontinuation if severe. Counsel patients to recognise warning symptoms (palpable purpura, facial swelling, generalised urticaria, breathing difficulty) and seek urgent assessment.
Drug Interactions
Because alirocumab is cleared by general protein catabolism rather than CYP-mediated metabolism, classical drug-drug interactions involving cytochrome enzymes, P-glycoprotein, or hepatic transporters do not apply. In clinical studies of alirocumab co-administered with atorvastatin or rosuvastatin, no clinically relevant changes in statin concentrations were observed. The clinically meaningful interactions are pharmacodynamic — additive effects when combined with other LDL-lowering agents — plus interactions specific to other PCSK9-targeted therapies and a few practical considerations.
Alirocumab has a clean systemic interaction profile with no clinically relevant CYP-mediated interactions. The single operational point worth remembering: in apheresis patients, alirocumab can be timed flexibly relative to the apheresis session — a practical advantage over evolocumab.
Monitoring
-
Lipid Panel (LDL-C, total cholesterol, HDL-C, triglycerides, non-HDL-C)
Baseline, then 4–8 weeks after initiation or dose change, then annually
Routine Confirm on-treatment LDL-C reduction. The PI states LDL-lowering effect can be measured as early as 4 weeks after initiation. For every-4-week dosing, schedule the follow-up draw close to the next dose to capture the trough, since LDL-C can vary across the dosing interval. -
Apolipoprotein B
Baseline (optional); repeat with major regimen change
Trigger-based Useful in patients with metabolic syndrome, hypertriglyceridaemia, or discordant LDL-C / non-HDL-C results — apo B better reflects atherogenic particle number in these settings. -
Lipoprotein(a)
Once at baseline (lifetime measurement)
Routine Lp(a) is largely genetically determined and stable across life. ODYSSEY OUTCOMES post-hoc analyses have suggested greater absolute MACE benefit with alirocumab in patients with higher baseline Lp(a). -
Liver Function Tests
Not routinely required; consider baseline and as clinically indicated
Trigger-based In pooled hypercholesterolaemia trials, liver-related disorders were reported in 2.5% of alirocumab-treated patients versus 1.8% on placebo, with ALT/AST >3× ULN in 1.7% versus 1.4%. The PI does not mandate routine LFT monitoring, but obtaining baseline values is reasonable, especially when concomitant statins are used. -
Creatine Kinase
Only if muscle symptoms develop
Trigger-based Myalgia is the principal >5% adverse reaction in the established CVD population (6% vs 5% placebo in ODYSSEY OUTCOMES). CK testing helps distinguish drug-related symptoms from coincidental statin-related myopathy. -
Glycaemic Status
Per cardiovascular and diabetes prevention guidelines
Routine No specific signal of new-onset diabetes attributed to alirocumab in pivotal trials. Continue routine cardiovascular surveillance. -
Blood Pressure
At each visit
Routine Routine cardiovascular monitoring; not specifically driven by alirocumab. -
Injection Site / Tolerability
First 1–3 doses, then PRN
Routine Inspect for erythema, induration, or signs of hypersensitivity. Most reactions occur early; persistent or worsening reactions warrant attention. -
Hypersensitivity Surveillance
Each visit (clinical assessment)
Routine Alirocumab carries specific FDA labelling for hypersensitivity vasculitis, angioedema (post-marketing), and serious reactions requiring hospitalisation. Counsel patients to recognise palpable purpura, facial swelling, generalised urticaria, or breathing difficulty. -
Anti-Drug Antibodies
Not routinely tested
Trigger-based ADA developed in 5.5% of adults in ODYSSEY OUTCOMES (NAb in 0.5%) and 3% of paediatric patients (no NAb). Routine testing is not recommended; consider only when LDL-C response unexpectedly attenuates despite confirmed adherence.
For routine alirocumab monitoring, two tests dominate: a baseline lipid panel and a follow-up panel 4–8 weeks after the first dose to confirm adequate LDL-C reduction. Once stability is demonstrated, annual lipid testing is sufficient for most patients in the absence of new symptoms or adherence concerns.
Contraindications & Cautions
Absolute Contraindications
- History of a serious hypersensitivity reaction to alirocumab or any of the excipients in Praluent — including prior hypersensitivity vasculitis, angioedema, or hypersensitivity reactions requiring hospitalisation
Relative Contraindications (Specialist Input Recommended)
- Severe hepatic impairment (Child-Pugh C) — pharmacokinetics not characterised; consider lipidology or hepatology input before initiation
- Severe renal impairment — no formal pharmacokinetic data; mechanistic concern is minimal but specialist input is advisable
- Pregnancy — IgG antibodies cross the placenta in increasing amounts during the second and third trimester; long-term LDL lowering is rarely time-critical and therapy is typically discontinued. A pregnancy registry is available (1-844-734-6643)
- Active malignancy under treatment — not a true contraindication, but defer initiation until oncology priorities are settled
Use with Caution
- History of allergy to monoclonal antibody biologics — observe the first 1–2 doses, ideally in a clinical setting; counsel on hypersensitivity warning signs
- Lactating patients — limited data; published evidence suggests breast-milk IgG is not substantially absorbed by the neonate, but a risk-benefit discussion is advisable
- Paediatric patients aged 8–11 years — administration must be performed by a trained caregiver. Adolescents 12–17 years should self-administer only by or under adult supervision
- HoFH in adults — alirocumab is approved as adjunctive therapy; clinical response depends on residual LDL-receptor function and may be limited in patients with two LDLR-null variants
Alirocumab does not carry an FDA boxed warning. However, the prescribing information explicitly identifies hypersensitivity vasculitis, angioedema, and hypersensitivity reactions requiring hospitalisation as labelled adverse reactions. This labelling is more specific than the equivalent warnings for evolocumab and reflects the post-marketing safety experience for alirocumab. Angioedema and influenza-like illness are listed in post-marketing experience. If signs or symptoms of serious hypersensitivity occur, discontinue treatment, treat per standard of care, and monitor until symptoms resolve.
Clinicians should counsel patients to recognise warning symptoms — palpable purpura or new-onset rash in dependent areas (vasculitis), facial, lip, or tongue swelling (angioedema), generalised urticaria, or breathing difficulty — and to seek emergency care if these develop.
Patient Counselling
Purpose of Therapy
Explain that alirocumab is a long-acting injection that lowers “bad” cholesterol (LDL) by helping the liver clear it from the blood more efficiently. It is added to — not a replacement for — a healthy diet, exercise, and any statin or other lipid-lowering medication the patient is already taking. Most patients see a meaningful drop in LDL-C, and in patients with a recent acute coronary syndrome, the medication has been shown to reduce the risk of future heart attacks, strokes, and chest-pain hospitalisations. Benefit accrues over time and depends on consistent dosing.
How to Take
Alirocumab is given as a subcutaneous injection in the abdomen, thigh, or upper arm using a single-dose pre-filled pen, available in 75 mg and 150 mg strengths. The 75 mg or 150 mg dose is delivered as a single injection every 2 weeks. The 300 mg every-4-week dose is delivered as two 150 mg pen injections at two different injection sites. Pens should be stored refrigerated (2–8°C / 36–46°F) and brought to room temperature for 30–40 minutes before injection to reduce stinging. Inject into a different site each time, avoid bruised, hard, red, or tender skin, and never re-use a pen. If a dose is missed, administer it within 7 days; if more than 7 days have passed, follow the missed-dose rule for your dosing interval as advised by your prescriber. Do not double-dose to compensate.
Sources
- U.S. Food and Drug Administration. Praluent (alirocumab) prescribing information (BLA 125559, s047, revised October 2025). Regeneron Pharmaceuticals, Inc. FDA label PDF (s047) Most current FDA-approved labelling and primary source for indications, dosing, adverse reaction rates, immunogenicity data, and pharmacokinetic parameters cited in this monograph.
- European Medicines Agency. Praluent (alirocumab) summary of product characteristics. EMA EPAR European prescribing reference covering EU-specific dosing presentations and special-population data.
- Regeneron press release. Praluent (alirocumab) injection receives FDA approval to treat children with genetic form of high cholesterol. 11 March 2024. Documents the expansion of the alirocumab paediatric HeFH indication to age 8 years and older — a younger threshold than the equivalent evolocumab indication.
- Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome (ODYSSEY OUTCOMES). N Engl J Med. 2018;379(22):2097-2107. DOI: 10.1056/NEJMoa1801174 Pivotal cardiovascular outcomes trial — 18,924 patients with recent acute coronary syndrome; primary composite MACE 9.5% vs 11.1% (HR 0.85; 95% CI 0.78–0.93; p=0.0003); mortality finding (3.5% vs 4.1%) was nominal and not statistically significant per the pre-specified hierarchy.
- Santos RD, et al. Alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: a randomized clinical trial. JAMA Pediatr. 2024. PubMed: 38315470 Phase 3 pivotal paediatric HeFH trial in 153 children aged 8–17 years; basis for the March 2024 paediatric indication. Demonstrated −43% LDL-C reduction with q2wk and −34% with q4wk dosing versus placebo.
- Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events (ODYSSEY LONG TERM). N Engl J Med. 2015;372(16):1489-1499. DOI: 10.1056/NEJMoa1501031 Long-term efficacy and safety in 2,341 high-risk patients on maximally tolerated statins; supported the original primary hypercholesterolaemia approval. At 24 weeks, alirocumab 150 mg q2wk reduced LDL-C by ~58% versus placebo.
- Moriarty PM, Thompson PD, Cannon CP, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients (ODYSSEY ALTERNATIVE). J Clin Lipidol. 2015;9(6):758-769. DOI: 10.1016/j.jacl.2015.08.006 Trial supporting alirocumab use in patients with documented statin intolerance, using a blinded statin/placebo rechallenge design.
- Kastelein JJP, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results from two phase 3 studies of alirocumab in heterozygous familial hypercholesterolemia. Eur Heart J. 2015;36(43):2996-3003. DOI: 10.1093/eurheartj/ehv370 Pivotal HeFH efficacy data in adults receiving maximally tolerated statin ± other lipid-modifying therapy. Pooled treatment difference at week 24 was −54% LDL-C versus placebo.
- Jukema JW, Szarek M, Zijlstra LE, et al. Alirocumab in patients with polyvascular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES trial. J Am Coll Cardiol. 2019;74(9):1167-1176. DOI: 10.1016/j.jacc.2019.03.013 Pre-specified subgroup analysis showing greatest absolute MACE reduction with alirocumab in patients with disease in multiple vascular beds (coronary plus peripheral or cerebrovascular).
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/Multisociety guideline on the management of blood cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. DOI: 10.1016/j.jacc.2018.11.003 Defines the role of PCSK9 inhibitors as second-line non-statin therapy in very high-risk ASCVD patients.
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2020;41(1):111-188. DOI: 10.1093/eurheartj/ehz455 European guidance with low LDL-C targets in very high-risk patients (<1.4 mmol/L), supporting earlier PCSK9 inhibitor use.
- Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering. J Am Coll Cardiol. 2022;80(14):1366-1418. DOI: 10.1016/j.jacc.2022.07.006 Practical algorithm for incorporating PCSK9 inhibitors, ezetimibe, bempedoic acid, and inclisiran into clinical practice.
- Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264-1272. DOI: 10.1056/NEJMoa054013 Foundational genetic study identifying PCSK9 loss-of-function as cardioprotective — the rationale for therapeutic PCSK9 inhibition.
- Lagace TA. PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells. Curr Opin Lipidol. 2014;25(5):387-393. DOI: 10.1097/MOL.0000000000000114 Review of the molecular mechanism by which PCSK9 promotes LDL-receptor degradation — context for alirocumab’s pharmacology.
- Goodman SG, Steg PG, Szarek M, et al. Safety of the PCSK9 inhibitor alirocumab: insights from 47,296 patient-years of observation. Eur Heart J Cardiovasc Pharmacother. 2024;10(4):342-352. DOI: 10.1093/ehjcvp/pvae025 Pooled safety analysis across the alirocumab clinical development programme; comprehensive long-term safety reference.
- Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab on cardiovascular outcomes after acute coronary syndromes: rationale and design of the ODYSSEY OUTCOMES trial. Am Heart J. 2014;168(5):682-689. DOI: 10.1016/j.ahj.2014.07.028 Trial design paper for ODYSSEY OUTCOMES; useful context on patient selection and the adaptive titration scheme.