Background Patients with homozygous familial hypercholesterolemia (HoFH) respond inadequately to existing drugs. We conducted a phase 3 study to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with HoFH. Methods Twenty-nine subjects enrolled into a single-arm, open-label study and maintained current lipid lowering therapy from six weeks before baseline through at least week 26. Lomitapide dose was escalated based on safety and tolerability from 5 mg to a maximum of 60 mg/day. The primary endpoint was mean percent change from baseline in LDL-C at week 26, after which patients remained on lomitapide through week 78 for safety assessment. Findings Twenty-three subjects completed weeks 26 and 78. The median dose of lomitapide was 40 mg/day. LDL-C was reduced by 50% from baseline at week 26 (4·3 ± 2·5 mmol/L vs. 8·7 ± 2·9 mmol/L, p<0.0001). Eight subjects achieved LDL-C <2·6 mmol/L at this time point. LDL-C was reduced by 44% at week 56 and 38% at week 78 (p<0.0001 for both). Gastrointestinal symptoms were the most common adverse event. Four patients had aminotransaminase > 5× ULN that resolved after dose reduction or temporary interruption of lomitapide. No subject permanently discontinued treatment due to liver abnormalities. Liver fat content assessed by nuclear magnetic resonance spectroscopy (NMRS; n=20) was 1·0 ± 1·3 % at baseline, 8·6 ± 8·1% at week 26 and remained stable up to week 78 (8·3± 5·3%). Interpretation These data demonstrate that lomitapide had a robust and durable efficacy in lowering LDL-C in patients with HoFH with an acceptable safety and tolerability profile.

In subjects with low HDL cholesterol levels, CETP inhibition with torcetrapib markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels, both when administered as monotherapy and when administered in combination with a statin.

No abstract

Inhibition of the microsomal triglyceride transfer protein by BMS-201038 resulted in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, owing to reduced production of apolipoprotein B. However, the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation.

Background Inability to tolerate statins because of muscle symptoms contributes to uncontrolled cholesterol levels and insufficient cardiovascular risk reduction. Bempedoic acid, a prodrug that is activated by a hepatic enzyme not present in skeletal muscle, inhibits ATP ‐citrate lyase, an enzyme upstream of β‐hydroxy β‐methylglutaryl‐coenzyme A reductase in the cholesterol biosynthesis pathway. Methods and Results The phase 3, double‐blind, placebo‐controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL‐Inhibiting Regimen) Serenity study randomized 345 patients with hypercholesterolemia and a history of intolerance to at least 2 statins (1 at the lowest available dose) 2:1 to bempedoic acid 180 mg or placebo once daily for 24 weeks. The primary end point was mean percent change from baseline to week 12 in low‐density lipoprotein cholesterol. The mean age was 65.2 years, mean baseline low‐density lipoprotein cholesterol was 157.6 mg/dL, and 93% of patients reported a history of statin‐associated muscle symptoms. Bempedoic acid treatment significantly reduced low‐density lipoprotein cholesterol from baseline to week 12 (placebo‐corrected difference, −21.4% [95% CI, −25.1% to −17.7%]; P <0.001). Significant reductions with bempedoic acid versus placebo were also observed in non–high‐density lipoprotein cholesterol (−17.9%), total cholesterol (−14.8%), apolipoprotein B (−15.0%), and high‐sensitivity C‐reactive protein (−24.3%; P <0.001 for all comparisons). Bempedoic acid was safe and well tolerated. The most common muscle‐related adverse event, myalgia, occurred in 4.7% and 7.2% of patients who received bempedoic acid or placebo, respectively. Conclusions Bempedoic acid offers a safe and effective oral therapeutic option for lipid lowering in patients who cannot tolerate statins. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02988115.

No abstract

Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.

Ground flaxseed has a modest but short lived LDL-C lowering effect, yet reduces Lp(a) and improves insulin sensitivity in hyperlipidemic adults. The HDL-C lowering effect of flaxseed in men warrants additional study.