geoffrey modest medical blogs

  This is an addition to the last blog on PCSK9 inhibitors and lipoprotein (a): I should have included this impressive study on PCSK9 inhibitors and their clinical benefit in Lp(a) reduction, a benefit independent of LDL reduction, in the Fourier study mentioned in the last blog (see  Lp(a) Fourier study PCSK9 dec events Circ2019  in dropbox, or DOI: 10.1161/CIRCULATIONAHA.118.037184)   --Lp(a) was measured in 25,096 patients randomized to the injectable PCSK9 inhibitor evolocumab vs placebo with a prespecified endpoint analysis to assess the relationship between Lp(a) levels, PCSK9 inhibition with evolocumab, and cardiovascular risk reduction, finding:     -- patients with higher Lp(a) levels were at increased risk of a cardiovascular event independent of their LDL levels     -- evolocumab reduced Lp(a) levels by 26.9%     -- there was a moderately positive correlation between the percent change in Lp(a) and LDL leve...

  A recent study found that the oral PCSK9 inhibitor Enlicitide decreased an array of adverse lipid markers including lipoprotein(a) (referred to as Lp(a)) in the phase-3 CORALreef HeFH study: see   lipid oral PCSK9 lipid effect JAMA2025  in dropbox, or doi:10.1001/jama.2025.20620   Details : -- 303 participants with genetically-confirmed heterozygous familial hypercholesterolemia (HeFH) who were at least 18 years old and were on statin therapy as well as many being on ezetimibe were randomized to the oral PCSK9 inhibitor enlicitide decanoate 20 mg once daily for 52 weeks versus placebo. Patients were instructed to take this medication on an empty stomach 30 minutes prior to eating     -- these patients had either an LDL level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease (ASCVD), or a level of 70 mg/dL or greater without a history of ASCVD -- this trial was conducted in 59 sites across 17 countries, screening pat...