— July 15, 2026 · FDA Approves the First Cholesterol-Lowering PCSK9 Pill

Table of Contents

1. At a Glance
2. What the FDA Approved, and When
3. What Was Tested
4. What Was Found, Number by Number
5. How It Works
6. How It Fits With Earlier Research
7. Dosing and Safety on the Label
8. What It Cannot Show, and What Remains Unknown
9. What the FDA and the Researchers Said
10. Sources and Primary Documents
11. Key Research Papers
12. Connections
13. Featured Videos

At a Glance

• What happened — FDA approval of enlicitide (active ingredient enlicitide decanoate), new drug application 220848, signed July 15, 2026. It is a new molecular entity: no drug with this active ingredient had been approved before.
• Approved use — added to diet and exercise to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).
• Form and dose on the label — one 20 mg tablet by mouth once a day, on an empty stomach in the morning.
• Main evidence — CORALreef Lipids (2,904 adults with or at high risk of artery disease) and CORALreef HeFH (303 adults with the inherited form), each 52 weeks, randomized 2:1 against placebo.
• Main result — LDL cholesterol at week 24 was 56 percentage points lower than placebo in the first trial and 59 points lower in the second.
• Side effects — in the larger trial, adverse reactions were about as common as with placebo; in the HeFH trial, diarrhea (7% vs 2%) and dizziness (9% vs 4%) were more frequent with the drug.
• Heart attacks and strokes — not yet shown. The CORALreef Outcomes trial (about 14,550 people) has an estimated primary completion date of November 29, 2029.
• Review path — Priority Review plus the FDA Commissioner’s National Priority Voucher pilot. The letter records the application as received June 22, 2026, 23 days before approval. No advisory committee meeting was held.

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What the FDA Approved, and When

The approval letter is addressed to the drug’s maker and refers to a new drug application “received June 22, 2026”. It states that the application “is approved, effective on the date of this letter,” and the electronic signature of Lisa B. Yanoff, MD, Deputy Director of the FDA’s Office of Cardiology, Hematology, Endocrinology, and Nephrology, carries the time stamp 07/15/2026 02:02:18 PM. The agency’s table of novel drug approvals for 2026 lists enlicitide decanoate as entry 26, approved 7/15/2026, “To reduce low-density lipoprotein cholesterol.”

The approved use, in the label’s words, is “as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).” In plain terms: the drug is approved to lower a blood number. Its label does not claim that it prevents heart attacks or strokes. The label adds one sentence about other drugs: that outcome trials have shown that lowering LDL cholesterol reduces major cardiovascular events “when treated with statins or monoclonal antibody proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors as an add-on to statin therapy.” That sentence describes earlier drug classes, not enlicitide itself.

The review was fast. The FDA’s July 17 news release says the drug “received Priority Review” and was “also reviewed under the Commissioner’s National Priority Voucher (CNPV) pilot program.” The voucher had been awarded on December 19, 2025, when the agency announced that “Enlicitide decanoate — an oral PCSK9 inhibitor for lowering LDL cholesterol” was one of two products receiving it. Under that pilot, the FDA says, “review decisions are targeted for completion within 1-2 months following submission of an application.” Going by the dates in the approval letter, this one took 23 days from receipt to approval.

The letter also records that the application was not sent to an outside advisory committee. It also sets out what the FDA requires for children: no studies are required in children with HeFH under 6 years old, and a placebo-controlled study in children and teenagers aged 6 to under 18 is deferred, with completion due by January 2036 and a final report by July 2036.

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What Was Tested

The label’s Clinical Studies section rests on two trials. Both compared a daily 20 mg tablet with a look-alike placebo for 52 weeks, assigned at random, with two people getting the drug for every one getting placebo. Neither patients nor doctors knew who was taking which. In both trials the main measure (the primary end point) was the percentage change in LDL cholesterol from the start of the trial to week 24.

CORALreef Lipids (Trial 1)

This multinational trial, published in the New England Journal of Medicine on February 5, 2026, enrolled adults who had already had a major event caused by artery disease (such as a heart attack or an ischemic stroke) and had LDL cholesterol of 55 mg/dL or more. It also enrolled adults at risk of a first such event with LDL of 70 mg/dL or more. Of the 2,909 people in the analysis, 1,935 received enlicitide and 969 placebo; 5 received neither. The label counts the 2,904 who were treated. The average age was 63, and 39% were women. The label adds that 50% had diabetes, 58% had already had a cardiovascular event and 42% were at increased risk of a first one. It also reports that 97% were taking a statin, 54% at high intensity. Average LDL at the start was 96 mg/dL. People already taking another PCSK9 drug were excluded.

CORALreef HeFH (Trial 2)

This trial, published in JAMA on January 13, 2026, enrolled 303 adults with heterozygous familial hypercholesterolemia. That is an inherited condition in which LDL cholesterol is high from birth. The trial ran at 59 sites in 17 countries between August 2023 and April 2025. Participants were randomized 202 to the drug and 101 to placebo. Their average age was 52.4, and 51% were female. Every participant was on a statin (81.5% at high intensity), and 64.4% were also taking ezetimibe. Average LDL at the start was 119 mg/dL, and 293 people (96.7%) completed the trial.

Supporting trials

A third phase 3 trial, CORALreef AddOn, appeared in the Journal of the American College of Cardiology (online March 30, 2026). It compared the pill with two other cholesterol-lowering pills, ezetimibe and bempedoic acid, used alone or together. It ran for 56 days in 301 adults already on statins. The label’s Clinical Studies section does not include it. An earlier phase 2b dose-finding trial (381 adults, 8 weeks, published in 2023) tested daily doses of 6, 12, 18 and 30 mg.

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What Was Found, Number by Number

A note on the numbers: trials like these report a between-group difference in percentage points. If LDL falls 57% in the drug group and rises 3% in the placebo group, the difference is about 60 points. After the trial’s statistical adjustments, the reported figure was 55.8 points.

CORALreef Lipids

• LDL at week 24: −57.1% with enlicitide (95% confidence interval −61.8 to −52.5) vs +3.0% with placebo (0.9 to 5.1). Adjusted difference −55.8 percentage points (−60.9 to −50.7; P<0.001).
• Other blood fats at week 24 (label, difference from placebo): non-HDL cholesterol −53 points (−55 to −51); apolipoprotein B, which counts the particles that carry cholesterol into artery walls, −50 points (−52 to −49).
• Week 52 and lipoprotein(a): the paper reports that the LDL change at week 52 and the change in lipoprotein(a) at week 24 were both significantly greater with the drug than with placebo (P<0.001). The abstract does not give the figures, and the full paper was not open to this report.
• A data-handling footnote: the label adds a later (post-hoc) analysis that set LDL values of zero or below to missing. Calculated LDL can produce such values when the true level is very low. In that analysis, the change was −60% vs +3%, a difference of −60 points (−62 to −57).
• Side effects: the paper reports that adverse events “did not appear to differ between the groups”. The label reports similar rates of adverse reactions and of stopping treatment because of them.

CORALreef HeFH

• LDL at week 24: −58.2% vs +2.6%; difference −59.4% (−65.6 to −53.2; P<.001).
• LDL at week 52: −55.3% vs +8.7%; difference −61.5% (−69.4 to −53.7).
• Non-HDL cholesterol at week 24: difference −53.0% (−58.5 to −47.4). Apolipoprotein B: −49.1% (−54.0 to −44.3).
• Lipoprotein(a) at week 24: median −24.7% vs −1.6%; difference −27.5% (−34.3 to −20.6).
• Side effects: any adverse event 77.7% vs 76.2%; serious adverse events 4.5% vs 4.0%; stopped because of an adverse event 2.0% vs 3.0%. According to the label, diarrhea (7% vs 2%) and dizziness (9% vs 4%) were the most common reactions that occurred more often with the drug.

CORALreef AddOn (56 days, against other pills)

• LDL change by day 56: enlicitide −64.6% (−68.3 to −60.9); bempedoic acid −6.3% (−13.5 to 0.8); ezetimibe −27.8% (−32.3 to −23.4); bempedoic acid plus ezetimibe −36.5% (−40.8 to −32.2). Enlicitide lowered LDL more than each comparison (all P<0.001). Adverse events were about as common in every group.

Phase 2b (8 weeks, 2023)

• Placebo-adjusted LDL change: −41.2% (6 mg), −55.7% (12 mg), −59.1% (18 mg) and −60.9% (30 mg). The label states that the 20 mg dose “achieved near-maximal reductions” in LDL.

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How It Works

LDL cholesterol travels in the blood inside tiny particles. The liver clears those particles by catching them with LDL receptors, docking sites on the surface of liver cells. A receptor pulls an LDL particle inside, lets it go, and normally returns to the surface to catch another. Dallas researchers Michael Brown and Joseph Goldstein worked out this system and shared the 1985 Nobel Prize for it. Inherited faults in the LDL receptor gene are one cause of familial hypercholesterolemia. Faults in the gene for apolipoprotein B, and, as described below, in the PCSK9 gene, are others.

PCSK9 is a protein made by the liver that tags LDL receptors for destruction. The label describes the drug’s action this way: “PCSK9 binds to the low-density lipoprotein receptors (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. By inhibiting the binding of PCSK9 to LDLR, enlicitide increases the number of LDLRs available to clear LDL-C, thereby lowering LDL-C levels.” With PCSK9 blocked, more receptors survive, and more LDL is pulled out of the blood. The label reports that single doses of 10 mg or more cut free PCSK9 in the blood by more than 90% within about half an hour to an hour.

Statins work by a different route: they slow the liver’s own production of cholesterol, and the liver responds by making more LDL receptors. That is why a PCSK9 blocker can lower LDL further in someone already taking a statin. Earlier PCSK9 drugs are given by injection. The best-studied are two antibodies, evolocumab and alirocumab, large proteins injected every two weeks or monthly that grab PCSK9 in the blood. Inclisiran, injected twice a year after the first doses, reduces the liver’s production of PCSK9.

Enlicitide is a macrocyclic peptide: a small chain of amino-acid building blocks closed into a ring. Molecules of this kind are hard to absorb through the gut, and the label puts its oral bioavailability at “approximately 1%”. In other words, about one hundredth of each dose reaches the blood. Each tablet contains sodium caprate, a fatty-acid salt that, in the label’s words, “facilitates the oral absorption”. Food gets in the way. Taking the tablet 30 minutes after a meal cut the drug’s total exposure in the blood by 48%. That is why the label gives a strict empty-stomach routine, described below. Once absorbed, the drug is barely broken down and leaves the body mainly through the kidneys.

The site’s animation Cholesterol, LDL and the Artery Wall shows how LDL particles enter the artery wall and build the plaque of atherosclerosis.

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How It Fits With Earlier Research

A gene found through families with very high cholesterol

PCSK9 was first described in 2003. That year a Montreal team described an enzyme called NARC-1, made in liver cells among other tissues. Months later, a French-led team showed that two mutations in its gene cause autosomal dominant hypercholesterolemia, an inherited form of very high LDL. Until then that condition had been linked only to faults in the LDL receptor gene or in the gene for apolipoprotein B. A 2005 paper described those family mutations as “probably gain-of-function mutations”: they make PCSK9 too active, and too many LDL receptors are destroyed.

The opposite mutation: lifelong low LDL and less heart disease

The same 2005 paper, from a Dallas group, asked whether mutations that switch PCSK9 off would have the opposite effect. Among 128 people with low LDL, the researchers found two such “nonsense” mutations. These mutations were carried by about 2% of African Americans and were linked to about 40% lower LDL. In 2006 the group reported 15 years of follow-up from the Atherosclerosis Risk in Communities study in the New England Journal of Medicine:

• Among 3,363 Black participants, the 2.6% who carried a PCSK9 nonsense mutation had 28% lower average LDL and an 88% lower risk of coronary heart disease (hazard ratio 0.11; 95% CI 0.02 to 0.81).
• Among 9,524 white participants, the 3.2% with a milder PCSK9 variant had 15% lower LDL and a 47% lower risk (hazard ratio 0.50; 0.32 to 0.79).

The authors concluded that “moderate lifelong reduction” in LDL was associated with a substantial reduction in coronary events. The PCSK9-blocking drugs described below were developed after these findings.

Lower LDL, fewer events, across many trials

The broader idea that lowering LDL prevents heart attacks rests on decades of statin trials. A 2010 analysis by the Cholesterol Treatment Trialists’ Collaboration pooled 26 randomized trials with about 170,000 participants. For each 1.0 mmol/L reduction in LDL (about 39 mg/dL), major vascular events fell by about a fifth (rate ratio 0.78; 95% CI 0.76 to 0.80), and all-cause deaths fell by 10% (rate ratio 0.90). The authors found no evidence of a threshold within the cholesterol range studied.

Injectable PCSK9 antibodies: the outcome trials

• FOURIER (2017): 27,564 people with established artery disease on statins were randomized to evolocumab injections or placebo, with a median follow-up of 2.2 years. LDL fell from a median of 92 to 30 mg/dL. The main composite of cardiovascular events occurred in 9.8% vs 11.3% (hazard ratio 0.85; 0.79 to 0.92). Cardiovascular death, heart attack or stroke: hazard ratio 0.80 (0.73 to 0.88).
• ODYSSEY OUTCOMES (2018): 18,924 people who had had an acute coronary syndrome 1 to 12 months earlier were randomized to alirocumab or placebo, with a median follow-up of 2.8 years. Events occurred in 9.5% vs 11.1% (hazard ratio 0.85; 0.78 to 0.93), and deaths were 3.5% vs 4.1% (hazard ratio 0.85; 0.73 to 0.98).
• VESALIUS-CV (online November 2025): 12,257 people with atherosclerosis or diabetes but no previous heart attack or stroke, with a median follow-up of 4.6 years. Coronary death, heart attack or ischemic stroke occurred in 6.2% vs 8.0% at five years (hazard ratio 0.75; 0.65 to 0.86).

These trials are the “monoclonal antibody” outcome trials the enlicitide label refers to. They tested different molecules given by injection. Whether the same benefit follows from this pill is what CORALreef Outcomes is designed to find out.

Inclisiran

Inclisiran blocks the liver’s production of PCSK9 rather than the protein itself. In the ORION-10 and ORION-11 trials (1,561 and 1,617 patients, published 2020), injections on day 1, day 90 and every six months lowered LDL by 52.3% and 49.9% at day 510. Its own outcome trials, ORION-4 (16,124 enrolled) and VICTORION-2 PREVENT (17,004 enrolled), were listed as active but no longer recruiting in their registry entries, and no outcome result had been reported.

The 2026 cholesterol guideline

Four months before the approval, on March 13, 2026, the American College of Cardiology, the American Heart Association and nine other organizations published a new dyslipidemia guideline, which this site covered in New Cholesterol Guideline Lowers LDL Targets. The guideline “retires and replaces” the 2018 cholesterol guideline. As reported at the time, it restored numeric LDL goals, including below 55 mg/dL for people at very high risk, and lists non-statin drugs for people who need more lowering on top of a statin. Its literature search ran from October to December 2024, before any of the enlicitide phase 3 results were published.

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Dosing and Safety on the Label

The following are facts from the FDA-approved prescribing information, reported as the label states them.

• Dose: one 20 mg tablet taken by mouth once daily. The label notes that the LDL-lowering effect “may be measured as early as 4 weeks after initiation.”
• How it is taken: on an empty stomach in the morning with water, black coffee or plain tea, swallowed whole (not split, crushed or chewed), with at least 30 minutes before any food or other drink. The label allows it to be taken with other medicines. For a missed dose, the label directs taking it as soon as possible, at least 30 minutes before the next food or drink, and never two doses on the same day.
• Contraindications: none listed.
• Drug interactions: no clinically meaningful interactions were seen with lithium, levothyroxine, digoxin, warfarin, atorvastatin, alendronate, lisinopril or oral semaglutide tablets.
• Kidneys and liver: mild, moderate and severe kidney impairment raise drug levels by an expected 5%, 11% and 26%, which the label calls “not clinically meaningful”. Moderate liver impairment did not change drug levels. Severe liver impairment was not studied.
• Pregnancy: the label states that the drug “may cause fetal harm” based on how it works, because it lowers cholesterol and possibly other substances the body makes from cholesterol. Human data are insufficient. Rat and rabbit studies showed no harm to the developing young at exposures 58 and 51 times the human level. The label directs that the drug be stopped when pregnancy is recognized unless the benefits outweigh the potential risks to the fetus.
• Breastfeeding: no human information.
• Children: safety and effectiveness not established.
• Older adults: of the 2,137 people treated with the drug in the placebo-controlled trials, 960 (45%) were 65 or older and 252 (12%) were 75 or older. The label reports no overall differences in safety or effectiveness.
• Other findings: no clinically significant change in the heart’s QT interval at four times the usual peak blood level; not carcinogenic in a 26-week mouse study; not mutagenic in standard tests.

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What It Cannot Show, and What Remains Unknown

• No heart-attack or stroke result yet. The approval is based on a lower LDL number, not on fewer cardiovascular events. The HeFH trial’s authors wrote that their trial “was not powered for analysis of major cardiovascular events; the effect of enlicitide on major cardiovascular outcomes is currently being assessed in a large, ongoing trial (CORALreef Outcomes trial; NCT06008756).”
• The outcomes trial. According to ClinicalTrials.gov, CORALreef Outcomes began on October 9, 2023, is active but no longer recruiting, and has an estimated enrollment of 14,550. Its main measure is the time to a first coronary death, heart attack, ischemic stroke, acute limb ischemia or major amputation, or urgent artery-opening procedure, followed for up to about six years. Its primary completion date is estimated at November 29, 2029.
• One year of data. The placebo-controlled trials lasted 52 weeks. Longer safety data are being gathered in an open-label extension study (estimated 3,000 participants, primary completion estimated October 2028) and in the outcomes trial.
• No direct comparison with the injections. Both main trials compared the pill with placebo on top of existing treatment. The active-comparator trial tested two other pills, not the injectable PCSK9 drugs, and lasted 56 days.
• Who was studied. The HeFH authors noted that their trial “specifically focused on participants with HeFH”, so its findings may not apply to everyone. The trials enrolled adults only; the label reports insufficient data in pregnancy and no study in severe liver impairment, and the pediatric study the FDA requires is not due to finish until 2036.
• Trial conditions vs daily life. The drug is absorbed poorly and depends on a strict empty-stomach routine. The trials report results under study conditions; how consistently that routine is followed outside a trial has not been measured.
• Who ran the trials. All three phase 3 trials were funded by the drug’s maker, and several authors were its employees. The JAMA paper states that the maker had a role in the design, the analysis, the manuscript and the decision to publish. The funding is disclosed in each paper.
• Very low LDL over many years. The label’s footnote about LDL values at or below zero shows that some participants reached very low calculated LDL levels. The CTT analysis found no excess of cancer or non-vascular deaths at low LDL in statin trials, but data on decades of very low LDL from this particular drug do not yet exist.

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What the FDA and the Researchers Said

Michael Davis, MD, PhD, Acting Director of the FDA’s Center for Drug Evaluation and Research, was quoted in the agency’s July 17 news release: “Cardiovascular disease remains the leading cause of death in the United States, and elevated LDL cholesterol is one of its most important modifiable risk factors.” He added: “This approval provides an additional treatment option for adults with hypercholesterolemia and reflects the FDA’s broader commitment to supporting meaningful advances in patient access and tackling chronic diseases.” The release also states that “PCSK9 inhibitors have previously been available only as injectable therapies.”

When the FDA awarded the priority voucher on December 19, 2025, FDA Commissioner Marty Makary, MD, MPH, said: “High health care costs and prescription drug prices threaten to undermine all the technological advancements we see in the medical field. We’re pleased to grant these vouchers to two products that may significantly contribute to our goal of improving the accessibility and affordability of healthcare in America.” The FDA documents read for this report do not state a price for the drug.

On the decision not to hold an advisory committee meeting, the approval letter says the application “was not referred to an FDA advisory committee because evaluation of the safety data when used in the treatment of hypercholesterolemia did not raise significant safety or efficacy issues that were unexpected for a drug of this class. In addition, there were no controversial issues that would benefit from advisory committee discussion.”

The CORALreef Lipids authors concluded that, in people who had a history of or were at risk for a first cardiovascular event, “treatment with the oral PCSK9 inhibitor enlicitide resulted in significantly lower LDL cholesterol levels than placebo at 24 weeks.” The HeFH authors concluded that the drug “was well tolerated and significantly reduced levels of LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a)” in adults with the inherited condition.

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Sources and Primary Documents

Every figure above comes from the FDA documents, the trial registry or the published papers (full text where open, otherwise the abstract), not from news coverage. The New England Journal of Medicine and the Journal of the American College of Cardiology papers were read in abstract form only.

1. US Food and Drug Administration (2026). Novel Drug Approvals for 2026, entry 26: enlicitide decanoate, approved 7/15/2026, “To reduce low-density lipoprotein cholesterol.” — FDA Novel Drug Approvals 2026
2. US Food and Drug Administration (July 15, 2026). NDA approval letter, NDA 220848, Reference ID 5834794; signed by Lisa B. Yanoff, MD. — Approval letter, NDA 220848 (PDF)
3. US Food and Drug Administration (July 2026). Prescribing information and patient information for enlicitide tablets, NDA 220848, revised 7/2026. — Prescribing information, NDA 220848 (PDF)
4. US Food and Drug Administration (July 17, 2026). FDA Approves First Oral PCSK9 Inhibitor to Lower LDL Cholesterol in Adults with High Cholesterol. FDA News Release. — FDA news release, July 17, 2026
5. US Food and Drug Administration (December 19, 2025). FDA Grants Two National Priority Vouchers. Press announcement. — FDA press announcement, December 19, 2025
6. Navar AM, Mikhailova E, Catapano AL, Banka P, Blom DJ, Cadena A, et al. (2026). A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide. New England Journal of Medicine 394(6):529-539. — doi:10.1056/NEJMoa2511002 · PubMed PMID: 41879224
7. Ballantyne CM, Gellis L, Tardif JC, Banka P, Navar AM, Asprusten EA, et al. (2026). Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA 335(2):129-139. — doi:10.1001/jama.2025.20620 · PubMed PMID: 41206969
8. Catapano AL, Mikhailova E, Navar AM, Banka P, Corral P, Saxena M, et al. (2026). Oral PCSK9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial. Journal of the American College of Cardiology 88(3):340-352. — doi:10.1016/j.jacc.2026.03.036 · PubMed PMID: 42017875
9. ClinicalTrials.gov. Cardiovascular outcomes study of enlicitide decanoate (CORALreef Outcomes), NCT06008756; record last updated April 23, 2026. — NCT06008756
10. ClinicalTrials.gov. CORALreef Lipids, NCT05952856, and CORALreef HeFH, NCT05952869 (both completed). — NCT05952856 · NCT05952869

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Key Research Papers

Background papers on PCSK9, LDL lowering and the earlier PCSK9 drugs, in the order the story uses them. Each entry was checked against PubMed and Crossref before it was written down.

1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, et al. (2003). The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proceedings of the National Academy of Sciences of the USA 100(3):928-933. — PubMed PMID: 12552133
2. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. (2003). Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nature Genetics 34(2):154-156. — PubMed PMID: 12730697
3. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH (2005). Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nature Genetics 37(2):161-165. — PubMed PMID: 15654334
4. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006). Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. New England Journal of Medicine 354(12):1264-1272. — PubMed PMID: 16554528
5. Brown MS, Goldstein JL (1986). A receptor-mediated pathway for cholesterol homeostasis. Science 232(4746):34-47. — PubMed PMID: 3513311
6. Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. The Lancet 376(9753):1670-1681. — PubMed PMID: 21067804
7. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. (2017). Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine 376(18):1713-1722. — PubMed PMID: 28304224
8. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. (2018). Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine 379(22):2097-2107. — PubMed PMID: 30403574
9. Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, et al. (2020). Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. New England Journal of Medicine 382(16):1507-1519. — PubMed PMID: 32187462
10. Ballantyne CM, Banka P, Mendez G, Garcia R, Rosenstock J, Rodgers A, et al. (2023). Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616. Journal of the American College of Cardiology 81(16):1553-1564. — PubMed PMID: 36889610
11. Bohula EA, Marston NA, Bhatia AK, De Ferrari GM, Leiter LA, Nicolau JC, et al. (2026). Evolocumab in Patients without a Previous Myocardial Infarction or Stroke. New England Journal of Medicine 394(2):117-127. — PubMed PMID: 41211925
12. Blumenthal RS, Morris PB, Gaudino M, Johnson HM, Anderson TS, Bittner VA, et al. (2026). 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology 87(19):2624-2757. — PubMed PMID: 41824590

PubMed Topic Searches

1. PubMed: Enlicitide
2. PubMed: Oral PCSK9 inhibitors
3. PubMed: PCSK9 loss-of-function variants and coronary heart disease
4. PubMed: PCSK9 inhibitor cardiovascular outcomes trials
5. PubMed: Heterozygous familial hypercholesterolemia and PCSK9

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Connections

• News Archive
• New Cholesterol Guideline Lowers LDL Targets — the March 2026 guideline report
• Cholesterol Management — LDL, statins and the other cholesterol drugs
• Cholesterol Management: History and Discovery — how the LDL story unfolded
• Lipid Panel — the blood test that measures LDL cholesterol
• Apolipoprotein B (ApoB) — counting the particles that carry cholesterol
• Lipoprotein(a) — the inherited particle the trials also measured
• Atherosclerosis — how plaque builds in artery walls
• Coronary Artery Disease — narrowing of the heart’s arteries
• Cardiovascular Disease — the leading cause of death the FDA cited
• Heart Attack — one of the events the outcomes trial counts
• Stroke — ischemic stroke, another counted event
• Goldstein & Brown — the LDL receptor discovery
• Cholesterol, LDL and the Artery Wall — interactive animation
• CAC, Statins and the Density Paradox — calcium scores and statin decisions
• CoQ10 and Statin Muscle Symptoms — research on a common statin side effect

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