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    Cholesterol-lowering drugs: statins, PCSK9, Lipfendra and more

    Statins remain the first-line cholesterol drug. If LDL stays too high, the 2026 US guideline recommends adding ezetimibe, bempedoic acid or a PCSK9 antibody, all of which have cut heart attacks and strokes in outcome trials.[1][2][3][4] Two new pills arrived in 2026, the oral PCSK9 inhibitor enlicitide (Lipfendra, US) and the CETP inhibitor obicetrapib (EU). Both lower LDL substantially, but their effect on heart attacks and strokes is not yet proven.[5][6][7]

    Editor reviewedStrict sourcingUpdated ExplainerHealth and medicine, GLP-1 and metabolic medicine, Life sciences

    There are now at least seven kinds of cholesterol-lowering medicine, from statins to pills approved in 2026.[1][5] This guide explains how each works and what trials show about LDL lowering and, more importantly, about heart attacks and strokes. Doses and results are those used in the trials named, in the populations studied.

    This page is general information, not medical advice. Do not start, stop or change a medicine without talking to a clinician. The NHS, for example, advises talking to a doctor or pharmacist before stopping statins.[8]

    How the evidence is judged

    Lowering a number is not the same as preventing a heart attack. Doctors trust a cholesterol drug most once a large randomised “outcome trial” shows fewer heart attacks, strokes or deaths. Several drugs below have that proof. The newest ones have so far only shown that they lower LDL.

    Across statin trials, each 1.0 mmol/L reduction in LDL lowered major vascular events by about 22% (rate ratio 0.78).[9] That relationship makes LDL a validated surrogate: Lipfendra, for example, was approved on LDL results while its outcome trial continues.[6] The CETP class shows why outcome trials still matter. Torcetrapib raised HDL by 72% but increased death from any cause (hazard ratio 1.58).[10] Anacetrapib produced only a modest benefit (rate ratio 0.91) despite doubling HDL.[11]

    Drug-by-drug comparison

    Drug or classHow it worksFormOutcome-trial evidence
    statinsLower the liver’s cholesterol production[12]Daily tabletYes: about 22% fewer major events per 1 mmol/L LDL[9]
    EzetimibeReduces cholesterol absorption in the gut[2]Daily tabletYes: IMPROVE-IT, 32.7% vs 34.7% at 7 years[2]
    Bempedoic acidATP citrate lyase inhibitor[4]Daily tabletYes in statin-intolerant patients: CLEAR Outcomes, HR 0.87[4]
    pcsk9-inhibitors: evolocumab, alirocumabAntibodies against PCSK9[3]Injection every 2 weeks (trial doses)Yes: FOURIER, ODYSSEY OUTCOMES, VESALIUS-CV[3][13][14]
    Inclisiran (Leqvio)Blocks the liver’s production of PCSK9[15]Injection on day 1, day 90, then every 6 months[15]Pending: ORION-4, VICTORION-2P[16]
    Enlicitide (Lipfendra)Oral macrocyclic-peptide PCSK9 inhibitor[5]Daily 20 mg tabletPending: CORALreef Outcomes[6]
    obicetrapibSelective CETP inhibitor[17]Daily 10 mg tabletPending: PREVAIL[18]

    Statins and add-on tablets

    statins lower the amount of cholesterol your body makes. The NHS lists atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin as the main types, usually taken once a day, long term.[12] Common side effects listed by the NHS include headaches, dizziness and muscle pain.[19] In blinded trials, however, more than 90% of muscle complaints among people on statins were not caused by the drug.[20]

    Ezetimibe added to simvastatin after acute coronary syndrome (IMPROVE-IT, 18,144 patients) cut the 7-year primary endpoint from 34.7% to 32.7% (HR 0.936).[2] Bempedoic acid in 13,970 statin-intolerant patients lowered LDL by 21.1 percentage points versus placebo and reduced major events (HR 0.87). Gout (3.1% vs 2.1%) and gallstones (2.2% vs 1.2%) were more common.[4]

    Injectable PCSK9 drugs

    The antibody evolocumab cut LDL by 59% and reduced cardiovascular events (HR 0.85) in FOURIER.[3] Alirocumab reduced recurrent events after acute coronary syndrome in ODYSSEY OUTCOMES (HR 0.85).[13] In 2025, VESALIUS-CV showed evolocumab also prevented first heart attacks and strokes in high-risk people without a prior event (HR 0.75).[14] Inclisiran lowered LDL by about 50% with twice-yearly injections in ORION-10 and ORION-11.[15] The 2026 US guideline notes that its effect on cardiac events is still being studied.[1]

    New pills in 2026

    • Enlicitide (Lipfendra). In CORALreef Lipids (2,909 adults), 20 mg daily lowered LDL by 55.8 percentage points more than placebo at 24 weeks. It also lowered apoB and Lp(a).[21] The FDA approved it in July 2026.[5] In the HeFH trial, diarrhoea and dizziness were more common than with placebo.[22] Merck says it is not yet known whether it reduces cardiovascular events.[6]
    • Obicetrapib. In BROADWAY (2,530 high-risk patients), 10 mg daily cut LDL by 32.6 percentage points more than placebo.[17] Combined with ezetimibe in one pill, it cut LDL by 48.6% versus placebo.[23] The European Commission approved both forms in September 2026.[7]

    Gene-editing approaches that aim to switch off cholesterol genes permanently are earlier in development. Eli Lilly bought Verve Therapeutics, which is developing a PCSK9 base editor, in 2025; see base-editing.[24] For severe hypertriglyceridemia, the FDA approved olezarsen (Tryngolza) in June 2026 to cut triglycerides and pancreatitis risk.[25]

    Next in the crash course

    Health & medicine

    Statins

    Statins are the first-line cholesterol drugs. How they work, the trial evidence on heart attacks and strokes, side effects and the muscle-pain question.

    More in Health & medicine

    Developing in Health

    Questions readers ask

    What is the first-line drug for high cholesterol?

    Statins. The 2026 US guideline adds nonstatin drugs only if lifestyle changes and statins do not lower LDL enough.[1]

    What can I take if I cannot tolerate statins?

    The NHS lists ezetimibe, fibrates, bempedoic acid, inclisiran, alirocumab and evolocumab as alternatives. In the CLEAR Outcomes trial of statin-intolerant patients, bempedoic acid reduced major cardiovascular events.[26][4]

    Is there a PCSK9 inhibitor pill?

    Yes. The FDA approved Merck's enlicitide (Lipfendra) in July 2026 as the first oral PCSK9 inhibitor. In its main trial it lowered LDL by about 56% versus placebo at 24 weeks. Whether it prevents heart attacks is still being studied.[5][22][6]

    Does inclisiran prevent heart attacks?

    Not yet shown. Inclisiran lowers LDL by about 50% with twice-yearly injections, but the 2026 US guideline notes it is still being studied to see whether this reduces cardiac events. Large outcome trials are under way.[15][1][16]

    Is obicetrapib approved?

    The European Commission approved obicetrapib (Ubeslo) and an obicetrapib-ezetimibe pill (Evlarco) in September 2026, the company's first approval worldwide.[7]

    Sources

    · 26 claims from 11 publishers

    Each numbered claim is a statement we checked against the sources listed with it. Tap a number in the text to see its sources in place.

    1. [1]

      If lifestyle and statins do not lower LDL cholesterol enough, the 2026 guideline recommends adding nonstatin therapy such as ezetimibe, bempedoic acid or a PCSK9 monoclonal antibody, and notes that inclisiran is still being studied to show whether its LDL lowering reduces cardiac events. confirmedas of 2026-10-11

    2. [2]

      In IMPROVE-IT (18,144 patients after an acute coronary syndrome, median follow-up 6 years), adding ezetimibe, which reduces intestinal cholesterol absorption, to simvastatin lowered the 7-year rate of the primary cardiovascular endpoint to 32.7% from 34.7% (hazard ratio 0.936). confirmedas of 2026-10-11

    3. [3]

      In FOURIER (27,564 patients with atherosclerotic cardiovascular disease on statins, median follow-up 2.2 years), the PCSK9 antibody evolocumab cut LDL cholesterol by 59% versus placebo to a median of 30 mg/dL and reduced the primary cardiovascular endpoint (hazard ratio 0.85); injection-site reactions were more common (2.1% vs 1.6%). confirmedas of 2026-10-11

    4. [4]

      In CLEAR Outcomes (13,970 statin-intolerant patients, median follow-up 40.6 months), bempedoic acid, an ATP citrate lyase inhibitor, lowered LDL cholesterol by 21.1 percentage points more than placebo and reduced major cardiovascular events (11.7% vs 13.3%; hazard ratio 0.87), but gout and gallstones were more common. confirmedas of 2026-10-11

    5. [5]

      The FDA approved Merck's enlicitide (Lipfendra) 20 mg tablets in July 2026 (FDA action date 15 July; Merck announced it on 16 July) to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, making it the first FDA-approved oral PCSK9 inhibitor. confirmedas of 2026-10-11

    6. [6]

      Merck states it is not yet known whether Lipfendra reduces cardiovascular illness and death; its CORALreef Outcomes trial has enrolled over 14,500 participants, with estimated primary completion in November 2029. confirmedas of 2026-10-11

    7. [7]

      On 21 September 2026 NewAmsterdam and Menarini announced that the European Commission had granted marketing authorisation for Ubeslo and Evlarco, the first regulatory approval of obicetrapib worldwide, with a requirement to submit final results of the PREVAIL outcomes trial. confirmedas of 2026-10-11

    8. [8]

      The NHS says stopping statins may affect cholesterol levels and advises talking to a doctor or pharmacist before stopping. confirmedas of 2026-10-11

      • Statins · NHS (UK National Health Service) · How statins work (retrieved 2026-10-11)
    9. [9]

      A Cholesterol Treatment Trialists' meta-analysis of 26 randomised statin trials (about 170,000 participants) found that each 1.0 mmol/L (about 39 mg/dL) reduction in LDL cholesterol cut the annual rate of major vascular events by just over a fifth (rate ratio 0.78) and all-cause mortality by 10%. confirmedas of 2026-10-11

    10. [10]

      The earlier CETP inhibitor torcetrapib raised HDL cholesterol by 72.1% but its outcome trial (15,067 patients) was stopped early because it increased cardiovascular events (hazard ratio 1.25) and death from any cause (hazard ratio 1.58). confirmedas of 2026-10-11

    11. [11]

      In REVEAL (30,449 adults on intensive statin therapy, median 4.1 years), the CETP inhibitor anacetrapib raised HDL cholesterol by 104% and modestly reduced major coronary events (10.8% vs 11.8%; rate ratio 0.91). confirmedas of 2026-10-11

    12. [12]

      The NHS describes statins as medicines that lower cholesterol by reducing the amount the body makes; the main types are atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin, taken as a once-daily tablet, usually long term. confirmedas of 2026-10-11

      • Statins · NHS (UK National Health Service) · How statins work (retrieved 2026-10-11)
      • Statins · NHS (UK National Health Service) · Types of statins (retrieved 2026-10-11)
      • Statins · NHS (UK National Health Service) · How statins work (retrieved 2026-10-11)
    13. [13]

      In ODYSSEY OUTCOMES (18,924 patients 1 to 12 months after an acute coronary syndrome on high-intensity statins, median follow-up 2.8 years), the PCSK9 antibody alirocumab reduced recurrent ischaemic cardiovascular events (9.5% vs 11.1%; hazard ratio 0.85). confirmedas of 2026-10-11

    14. [14]

      In VESALIUS-CV (12,257 patients with atherosclerosis or diabetes but no previous heart attack or stroke, median follow-up 4.6 years), evolocumab lowered the risk of a first major cardiovascular event versus placebo (5-year estimate 6.2% vs 8.0%; hazard ratio 0.75), with no evidence of a difference in safety events; results were published in November 2025. confirmedas of 2026-10-11

    15. [15]

      Inclisiran blocks the liver's production of PCSK9; in the ORION-10 and ORION-11 trials (1,561 and 1,617 patients on maximum tolerated statins), injections on day 1, day 90 and every 6 months cut LDL cholesterol by about 50% versus placebo, with more injection-site reactions. confirmedas of 2026-10-11

    16. [16]

      Two large inclisiran outcome trials were active but not recruiting as of October 2026, ORION-4 (16,124 participants, estimated primary completion October 2026) and VICTORION-2P (17,004 participants, estimated primary completion May 2027). confirmedas of 2026-10-11

    17. [17]

      In BROADWAY (2,530 patients with ASCVD or heterozygous familial hypercholesterolemia on maximum tolerated lipid-lowering therapy), obicetrapib 10 mg daily, a selective CETP inhibitor, lowered LDL cholesterol by 32.6 percentage points more than placebo at day 84, with similar adverse-event rates. confirmedas of 2026-10-11

    18. [18]

      NewAmsterdam said in May 2026 that it would run an interim analysis of the PREVAIL cardiovascular outcomes trial (over 9,500 patients) in the fourth quarter of 2026, expects to report the result in the first quarter of 2027, and anticipates completion by the end of 2027 if the trial does not stop early for efficacy. confirmedas of 2026-10-11

    19. [19]

      The NHS says statins should not be taken by people with severe liver disease or who are pregnant or trying to get pregnant, and lists common side effects including headaches, dizziness, nausea, tiredness, digestive problems, muscle pain and sleep problems. confirmedas of 2026-10-11

      • Statins · NHS (UK National Health Service) · Who may be offered statins (retrieved 2026-10-11)
      • Statins · NHS (UK National Health Service) · Side effects of statins (retrieved 2026-10-11)
    20. [20]

      A 2022 individual-participant meta-analysis of 19 double-blind statin-versus-placebo trials found statins caused a small excess of mostly mild muscle pain, mainly in the first year, and that more than 90% of muscle-symptom reports among people on statins were not due to the statin. confirmedas of 2026-10-11

    21. [21]

      In the CORALreef Lipids trial (2,909 adults with or at risk of atherosclerotic cardiovascular disease), oral enlicitide 20 mg daily lowered LDL cholesterol by 55.8 percentage points more than placebo at week 24, also lowered non-HDL cholesterol, apolipoprotein B and Lp(a), and adverse events did not appear to differ from placebo. confirmedas of 2026-10-11

    22. [22]

      Merck reported that Lipfendra reduced LDL cholesterol by 56% versus placebo at week 24 in CORALreef Lipids and by 59% in CORALreef HeFH; in CORALreef HeFH, diarrhoea (7% vs 2%) and dizziness (9% vs 4%) were more common than with placebo. confirmedas of 2026-10-11

    23. [23]

      In the TANDEM trial (407 participants, 84 days), a fixed-dose pill of obicetrapib 10 mg plus ezetimibe 10 mg lowered LDL cholesterol by 48.6% versus placebo. confirmedas of 2026-10-11

    24. [24]

      On 17 June 2025 Eli Lilly agreed to acquire Verve Therapeutics for $10.50 per share in cash plus a contingent value right of up to $3.00 per share; Verve's lead program VERVE-102 is designed to permanently turn off the PCSK9 gene in the liver to lower cholesterol. confirmedas of 2026-10-10

    25. [25]

      On 24 June 2026 the FDA approved Ionis's olezarsen (Tryngolza), a once-monthly self-injected drug, as an adjunct to diet to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (triglycerides of 500 mg/dL or more). confirmedas of 2026-10-11

    26. [26]

      The NHS lists alternatives for people who cannot take statins, including tablets such as ezetimibe, fibrates and bempedoic acid, and injections such as inclisiran, alirocumab and evolocumab. confirmedas of 2026-10-11

      • Statins · NHS (UK National Health Service) · Alternatives to statins (retrieved 2026-10-11)
      • Statins · NHS (UK National Health Service) · Alternatives to statins (retrieved 2026-10-11)
    Revision history (1)
    1. Page created.

    Created Oct 11, 2026. Last reviewed by an editor on Oct 11, 2026. Next scheduled review: Jan 11, 2027.

    Cite this page

    "Cholesterol-lowering drugs: statins, PCSK9, Lipfendra and more." ContentLora, updated Oct 11, 2026. https://contentlora.com/explain/cholesterol-lowering-drugs-guide

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