Recent Clinical Advances in Reducing Risk for Dyslipidemia

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Feb 15, 2022

Peter Toth, preventive cardiology leader with PCSK9 and LDL expertise, and Erin Michos, cardiovascular prevention clinician-scientist, discuss nonstatin therapies and practical implementation. They cover PCSK9 inhibitors vs apheresis, inclisiran and bempedoic acid, managing triglycerides and lipoprotein(a). They also tackle access barriers and safety of very low LDL levels.

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ANECDOTE

Mr L Shows Severe FH With High Lp(a) Despite Therapy

Case of Mr L illustrates refractory heterozygous FH with metabolic dyslipidemia and very high Lp(a) after MI at 36.
Mr L: on high-intensity statin plus ezetimibe with LDL 160 mg/dL, triglycerides 190 mg/dL, and Lp(a) >95 mg/dL.

ADVICE

Add PCSK9 When Statin Plus Ezetimibe Is Insufficient

Use nonstatin therapies when statin plus ezetimibe leave LDL uncontrolled.
Erin Michos: PCSK9 inhibitors lower LDL 50–60% and inclisiran (siRNA) offers twice-yearly dosing to improve adherence.

INSIGHT

PCSK9 Therapy Lowers Lipoprotein A Too

PCSK9 inhibitors also lower lipoprotein(a) which may reduce risk beyond LDL lowering.
Erin Michos: PCSK9s reduce Lp(a) roughly 25% and may be important for patients with elevated Lp(a).

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In this episode, host Dr. Laurence Sperling speaks with Drs Erin Michos and Peter Toth about optimal use of newer dyslipidemia therapies.

Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/958749). The topics and discussions are planned, produced, and reviewed independently of our advertiser. This podcast is intended only for US healthcare professionals.

Resources

Cholesterol Treatment Trial: Efficacy and Safety of More Intensive Lowering of LDL Cholesterol: A Meta-analysis Of Data From 170,000 Participants in 26 Randomised Trials https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988224/

IMPROVE-IT: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes https://www.nejm.org/doi/full/10.1056/nejmoa1410489

ODYSSEY: Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome https://www.nejm.org/doi/full/10.1056/nejmoa1801174

FOURIER: Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk -- FOURIER https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2017/03/16/00/46/FOURIER

Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037184

ORION: Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol https://pubmed.ncbi.nlm.nih.gov/32187462/

CLEAR Wisdom: Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865290/

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121276/

CLEAR Outcomes: Rationale and Design of the CLEAR-Outcomes Trial: Evaluating the Effect of Bempedoic Acid on Cardiovascular Events in Patients With Statin Intolerance https://pubmed.ncbi.nlm.nih.gov/33470195/

CLEAR Wisdom: Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination in Patients With Hypercholesterolemia and High CVD Risk Treated With Maximally Tolerated Statin Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865290/

Bempedoic Acid and Ezetimibe -- Better Together https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203625/

REDUCE-IT: Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia https://www.nejm.org/doi/full/10.1056/nejmoa1812792

STRENGTH: Long-Term Outcomes Study to Assess Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia -- STRENGTH https://www.acc.org/latest-in-cardiology/clinical-trials/2020/11/11/21/29/strength

JELIS: Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic Patients (JELIS): A Randomised Open-Label, Blinded Endpoint Analysis https://pubmed.ncbi.nlm.nih.gov/17398308/

PROMINENT: Rationale and Design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) Study https://pubmed.ncbi.nlm.nih.gov/30342298/

How Low Is Safe? The Frontier of Very Low (

Cholesterol: The Race to the Bottom https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab446/6335767?searchresult=1

SPARCL: High-Dose Atorvastatin After Stroke or Transient Ischemic Attack https://www.nejm.org/doi/full/10.1056/nejmoa061894

EBBINGHAUS: Cognitive Function in a Randomized Trial of Evolocumab https://www.nejm.org/doi/full/10.1056/nejmoa1701131

PROSPER: Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER): A Randomized Controlled Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)11600-X/fulltext

Achievement of Very Low Low-Density Lipoprotein Cholesterol Levels https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.044275